Photocatalyst-Free, Visible-Light-Mediated C–H Perfluoroalkylation of Quinazolin-4(3H)-ones with perfluoroalkyl Iodides

Abstract

A practical and sustainable photocatalyst-free protocol for photoinduced synthesis of perfluoroalkylated quinazolin-4(3H)-ones is described starting from quinazolin-4(3H)-ones. A wide range of substituted or fused-quinazolinones is found to be compatible, providing the corresponding mono- and bis-perfluoroalkylated compounds in moderate yields. This visible-light-mediated C–H perfluoroalkylation allows an environmentally friendly and straightforward access to an array of unprecedented functionalized quinazolinone scaffolds, presenting attractive features for drug discovery. Control experiments demonstrated that a radical mechanism is involved in the reaction mechanism.

The incorporation of fluorinated moieties into molecular frameworks drastically modifies their physical and chemical properties and usually enhances the lipophilicity and bioavailability of drug molecules, as well as hydrolytic and metabolic stability.[1] A slight modification of the core motif triggered by the incorporation of a perfluoroalkylated unit often results in better medicinal candidates in comparison with the parent compound.[2] Compared to metal-mediated or -catalyzed cross-coupling reactions with pre-functionalized heteroarenes,[3] the synthesis of fluoro-containing heteroarenes from a direct C–H perfluoroalkylation strategy represents an appealing approach that provides a powerful tool in both pharmaceutical manufacturing and material science.[4] However, decisive limitations are associated with metal-catalyzed perfluoroalkylation methodologies. For example, R_f–metal species are very unstable and readily decompose even at low temperatures via α- or β-elimination of fluoride[5] and the use of expensive noble metals is often required. Besides, a lack of selectivity and a restricted scope of electron-rich heteroarenes was observed in several cases as well as the use of an excess of the substrates, hampering industrial applications.[6] Nevertheless, since perfluoroalkylated compounds are increasingly common structural scaffolds in pharmaceuticals, tremendous progress has been made toward the incorporation of perfluoralkyl groups into heteroaromatics compounds over the last decade, using innovative reaction conditions.[7] In this context, the development of visible-light-mediated C–H perfluoroalkylation has seen a flurry of attention in the very recent years as a powerful and an environmentally friendly activation strategy.[8] [9] Quinazolinone backbones, widely found in bioactive molecules, pharmaceuticals, and natural products, have emerged as a privileged structure due to their wide-ranging biological activities (Figure [1]).[10] Their occurrence mainly results from the effect of the azine’s properties associated with its adorning substituents. Due to their potential therapeutic applications, the development of straightforward and innovative functionalization of quinazolinones is still required for organic and medicinal chemists.

A great deal of C2-H functionalization strategies for the modulation of quinazolin-4-ones have been developed over the past decade.[11] The majority of these current methods require the use of transition metals, stoichiometric oxidants, and harsh reaction conditions. In contrast, the development of methods for the C–H functionalization of the benzene moieties of the quinazolinone remains sparse.

In addition, to date, synthetic routes available for the introduction of a perfluoroalkyl group into quinazolin-4(3H)-ones are limited. The reported strategies are mostly based on condensation reactions, including the cyclization of various anthranilic acid derivatives (Scheme [1]).[12] In 2004, the photochemical synthesis of fluorinated quinazolin-4-ones was described starting from 5-phenyl-3-perfluoroalkyl-1,2,4-oxadiazoles through a photoinduced electron-transfer process.[12d] Despite these achievements, it was noted that not a single approach for direct C–H perfluoroalkylation of quinazolin-4(3H)-ones has been reported. Owing to the great importance of quinazolinones as bioactive compounds, we described herein the first direct C–H perfluoroalkylation of quinazolin-4(3H)-one derivatives under mild and eco-friendly conditions.

Taking advantage of the well-known activation of perfluoroalkyl halides through photoactive electron-donor-acceptor (EDA) complexes,[13] a photocatalyst-free, visible-light photolytic process was tested by adding the perfluoroalkyl iodide and quinazolin-4(3H)-one 1a in the presence of a base. The reaction mixture was irradiated under blue LEDs at 425nm at room temperature with a range of bases and solvents for 24 h (Table [1], entries 1–18). This sustainable strategy, which should not require external photosensitizers, is based on the potential ability of the quinazolin-4-ol anion, generated upon base-mediated deprotonation of 1, to serve as a donor for EDA complex formation.

Table 1 Representative Results for the Optimization of the Reaction Conditions^a

Entry	Base	Solvent	Overall isolated yield (2a/3a/4a) (%)
1	KOAc	DMSO	12 (12/0/0)
2	LiOtBu	DMSO	20 (20/0/0)
3	K3PO4	DMSO	44 (32/4/7)
4	Na2CO3	DMSO	17 (17/0/0)
5	K2CO3	DMSO	42 (33/3/6)
6	Cs2CO3	DMSO	47 (31/7/9)
7	NaOH	DMSO	13 (13/0/0)
8	DABCO	DMSO	34 (21/12/1)
9	K2CO3	DMF	trace
10	K2CO3	DMA	NR
11	K2CO3	NMP	NR
12	K2CO3	MeCN	16 (16/0/0)
13	DABCO	MeCN	43 (28/12/3)
14	DABCO	MeCN/C6F14	43 (28/12/3)
15	K2CO3	MeOH	18 (18/0/0)
16	K2CO3	DMSO/H2O	12 (12/0/0)
17	K2CO3	acetone	23 (23/0/0)
18	K2CO3	DCM	5 (5/0/0)
19b	K2CO3	DMSO	53 (33/8/12)
20c	K2CO3	DMSO	65 (33/13/19)

^a Reaction conditions (unless otherwise specified): 1a (0.42 mmol, 1.0 equiv), C₆F₁₃I (1.27 mmol, 3.0 equiv), base (0.84 mmol, 2.0 equiv), solvent (3 mL), under a N₂ atmosphere, 24 h.

^b The reaction was performed at 40 °C.

^c The reaction was performed at 50 °C.

KOAc and NaOH were found to be the less effective bases (Table [1], entries 1 and 7), whereas inorganic bases such as K₃PO₄ or carbonates (entries 3, 5, and 6) led to the best overall yield (42–47%). Using K₂CO₃, the C8-perfluoroalkylated quinazolin-4-one 2a was isolated in 33% yield along with traces of the bis-perfluoroalkylated isomers 3a and 4a. Nevertheless, this strategy could be useful in a late-stage functionalization setting (i.e., SAR for medicinal chemistry efforts) as all the isomers can be easily separated by column chromatography on silica gel. Of the various solvents screened, DMSO was found to give the best results. The reaction was totally suppressed in DMF, DMA or NMP (entries 9–11), whereas acetone, acetonitrile and MeOH led to lower yields (entries 17, 12–15). In consideration of the solubility problems, a mixed solvent of DMSO/water with a 6:1 ratio was tested but resulted in a low yield (entry 16). Finally, varying the temperature highlighted its effect on the total conversion, with an optimization at 50 °C (65% overall yield; entry 20). An increase of the temperature above 50 °C led to lower conversion and further degradation (see the Supporting Information).

Further optimization studies, carried out using higher and lower quantity of reagents and bases and varying time as well as visible light with other wavelengths, resulted in lower reactivity (see the Supporting Information). The photolytic nature of the reaction was also verified as no reaction occurred in the dark. The addition of amines such as TMEDA or NEt₃, or a phosphine as additives known for the formation of a noncovalent interaction initiated single-electron transfer (SET) perfluoroalkylation,[9k] [p] did not improve the efficiency of the reaction (see the Supporting Information). This result is in agreement with the formation of an active EDA complex arising from the association of in situ generated deprotonated quinazolin-4(3H)-ones and the perfluoroalkyl iodides in the ground state. During all the optimization studies, the starting material 1a was always recovered (almost 30%) and the overall isolated yield never exceeded 65%. The inability of the reaction to complete, even after longer reaction time or the use of an excess of reagents, is correlated to the ability of product 2a to inhibit the process. Indeed, quinazolinones have been known to exhibit a strong absorption in the visible region, allowing a substrate-mediated energy-transfer process.[14] Inspired by Melchiorre’s results dealing with photochemical perfluoroalkylation of α-cyanoacetates in a biphasic system,[15] tetradecafluorohexane was added to the reaction mixture containing DABCO in MeCN (in a 4:1 ratio) in order to collect 2a in the perfluorinated phase (entry 14).[16] Nevertheless this combination did not positively affect the reactivity and the yield of the perfluoroalkylation was not improved in our case (see the Supporting Information for details).

With these optimized reaction conditions in hand, the scope of the substrates was investigated to evaluate the potential of the photoinduced C–H perfluoroalkylation (Scheme [2]). 5-Methylquinazolin-4(3H)-one 1b was first tested under the standard conditions and transformed into the mono- and di-perfluorohexylated compounds in 61% combined yield, respectively (2b and 4b). The reaction of various C6/C7-substituted quinazolin-4-ones with 3 equivalents of C₆F₁₃I in DMSO at 50 °C afforded the C8-perfluoroalkylated products 2c–k in isolated yields ranging from 15 to 47% within 24 h. Under these conditions, numerous quinazolinones are amenable to this process.

Depending on the substituent, the 5,8-bis-perfluoroalkylated quinazolin-4(3H)-one was also isolated in lower yield. The origins of the regioselectivity are not fully explained, but steric hindrance clearly has an impact on it, as the second perfluoroalkylation never occurs at C7 or C5 in the case of 6-substituted quinazolinones with bulky substituents. Considering the electrophilic character of perfluoroalkyl radicals (R_f ^.), the reaction is, not surprisingly, less efficient with compound 1k, bearing an electron-withdrawing substituent. Halogens were found to be compatible with the reaction conditions, but with chlorine, bromine, or iodine at C6, a competitive dehalogenation occurred, probably during the second perfluoroalkylation reaction. The most plausible pathway could reside in a homolytic cleavage taking place after the SET process. To extend the application of this reaction, we examined the analogous perfluoroalkylation reactions with 9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile 5. The global conversion (82%) was better than those observed with quinazolin-4-ones (15–61%) and the C–H perfluoroalkylation reaction gave regiochemical mixtures with the major isomer 6a at C5 isolated in 64% yield. Although compound mixtures are obtained in many cases, it is often an advantage to synthesize distinct analogs that can proceed into biological screening as they are readily separated using classical separation techniques.

The scope of this mild C–H perfluoroalkylation protocol was next investigated using quinazolin-4(3H)-ones 1a,d and the thiazolo-quinazolinone derivative 5, and the tolerance of various perfluoroalkyl iodide reagents was then explored (Scheme [3]). This study showed that the reaction is not limited to perfluorohexylation, since different chains of perfluoroalkyl groups were also compatible under the standard conditions and gave the corresponding products 2aa–db and 6b–d in acceptable yields. The bis-perfluoroalkylation was again observed with 1a as the substrate. Regioselectivity was obtained when the position at C6 on the azine was blocked, such as in derivative 1d. 9-Oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile 5 can also undergo the C–H perfluoroalkylation with short-chain groups with good conversion (69–80%) leading to the 5-perfluoroalkylated compounds 6b–d as the major isomer. As differing regioisomers can have different binding effects in biological targets, the result obtained with compound 5 is also useful.

To gain insight into the reaction mechanism, a series of control experiments were performed. Reactions conducted in the presence of a typical radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) shut down the reaction (Scheme [4a]). Mechanistic experiments can be rationalized in terms of a radical-involved C–I cleavage. The reaction of the N ³-benzylquinazolin-4-one with R_fI failed to produce the corresponding perfluorinated compound in good yield (Scheme [4b]) and clearly demonstrated the pivotal role of the N–H bond for the formation of the EDA complex. By analogy to the reactivity of halogeno-perfluoroalkylated reagents with Lewis bases, the formation of a SM⋅R_fI adduct via halogen bonding between R_fI and the quinazolin-4-one anion could be envisioned. In addition, no reaction took place with 2-phenylquinazolinone 1o, even on the phenyl ring (Scheme [4c]). When compound 2a reacted with C₆F₁₃I under the standard conditions, bis-perfluorohexylated compounds 3a and 4a were obtained in similar yields to those observed starting from 1a (see the Supporting Information). This result is consistent with the conclusion that the mono-perfluoroalkylated compound is the key intermediate involved in the bis-perfluoroalkylation process.

Based on previous works[9m] [n] and the results of control experiments, we proposed a plausible mechanism for the radical perfluoroalkylation (Scheme [5]). First, the iodoperfluoroalkane can form halogen bond complexes with the nitrogen anion of the deprotonated quinazolin-4(3H)-one as a Lewis base employing the lone electron pair to interact with the σ* antibonding orbital of the C–I bond. These complexes can be excited under visible-light irradiation and undergo single-electron transfer (SET) to produce the perfluoroalkyl radical, which is trapped by the heterocycle. A second electron transfer process affords an iodine species that gives the expected product 2a after a proton loss.

The synthetic utility of perfluoroalkylquinazolin-4-ones was finally evaluated through the conversion of 8-perfluorohexylquinazolinone 2a into the corresponding N ⁴-benzylaminoquinazoline 7 upon treatment with POCl₃ followed by the addition of benzylamine (Scheme [6]). Meanwhile, the synthesis of N-protected perfluorohexyl-quinazolin-4-ones was also realized and the N ³-benzyl and N ³-pyridinyl derivatives 2n and 8–10 were obtained in yields ranging from 58 to 85% starting from 2a–4a.

In summary, we have developed a mild and environmentally benign process as a suitable alternative to some classical methods for the synthesis of new perfluoroalkyl-quinazolin-4(3H)-ones as high-value compounds in medicinal chemistry. This visible-light-mediated, photocatalyst-free C–H perfluoroalkylation allows straightforward access to an array of unprecedented functionalized quinazolinone derivatives, presenting attractive features for drug discovery. Control experiments demonstrated that a radical mechanism is involved in the reaction mechanism. Before this study, no direct perfluoroalkylation of the quinazolinone nucleus had been reported at the different positions of the ring. Initial studies of their structure–activity relationships as kinase inhibitors will be realized in due course.

All reactions were carried out under inert atmosphere of argon or nitrogen and monitored by thin-layer chromatography with silica gel 60 F254 pre-coated aluminum plates (0.25 mm). Visualization was performed under UV light at 254 and 312 nm. All chemical reagents and solvents used in this study were obtained from commercial sources and used as received unless otherwise stated. Microwave experiments were conducted in a commercial microwave reactor designed for synthetic chemistry: The Biotage Inititor reactor is a monomode cavity with a microwave power delivery system ranging from 0 to 300 W allowing pressurized reactions (1–30 bar) to be carried out in sealed glass vials (0.5–30 mL) equipped a snap-cap and a silicon septum. The temperature (0–300 °C) was monitored via a contactless infrared sensor. Temperature, pressure, and power profiles were edited and monitored through a screen control panel.

Purifications were carried out with an Interchim Puriflash 215 equipped with a dual UV/Vis spectrophotometer (200–600 nm), a fraction collector (176 tubes), a dual piston pump (1 to 200 mL/min, P _max= 15 bar) allowing quaternary gradients, and an additional inlet for air purge. Samples could be introduced in liquid or solid mode. Purification was edited and monitored with an integrated panel PC with a touch screen using the control software ‘Interchim Software’. Biotage SNAP flash chromatography cartridges (KP-Sil, normal phase, 10 to 340 g) were used for the purification process.

Melting points of solid compounds were measured with a WME Köfler hot-stage with a precision of ±2 °C and are uncorrected. IR spectra were recorded with a PerkinElmer Spectrum 100 Series FT-IR spectrometer. Liquids and solids were applied on a Single Reflection Attenuated Total Reflectance (ATR) accessory. Absorption bands are given in cm^–1. ¹H, ¹³C and ¹⁹F NMR spectra were recorded with a Bruker Avance 300 MHz, at 300, 75.4 and 282 MHz, respectively. Abbreviations used for peak multiplicities are s: singlet, d: doublet, t: triplet, q: quadruplet and m: multiplet. Coupling constants J are in Hz, and chemical shifts are given in ppm and calibrated with DMSO-d ₆ (residual solvent signals) or CDCl₃. Mass spectra analysis was performed by the Mass Spectrometry Laboratory of the University of Rouen. Mass spectra (EI) were recorded with a Waters LCP 1er XR spectrometer.

Procedures

Quinazolinones 1a–c and 1g–1m and the thiazolo[5,4-f]quinazolin-9(8H)-one 5 were synthesized according to reported procedures.[17] Quinazolinones 1d–f were synthesized in a two-step procedure by using the following general methods A and B. 6-Phenylquinazolin-4(3H)-one (1e) was synthesized according to a reported procedure.[18]

General Method A

In a sealed microwave vial, a mixture of 6-bromoquinazolin-4(3H)-one (400 mg, 1.27 mmol, 1 equiv), boronic acid (1.50 mmol, 1.2 equiv), K₂CO₃ (526 mg, 3.81 mmol, 3 equiv), Pd(PPh₃)₂Cl₂ (91 mg, 0.13 mmol, 0.1 equiv), PPh₃ (66 mg, 0.26 mmol, 0.1 equiv) and NBu₄Cl (208 mg, 0.75 mmol, 0.1 equiv) in toluene/water (2 mL/2 mL) was heated at 120 °C for 2 days. The crude product was extracted with DCM, dried over MgSO₄, concentrated under vacuum, and purified by flash chromatography on silica gel.

General Method B

In a sealed microwave vial, the N-benzylquinazolinone (1 equiv) and AlCl₃ (4–5.5 equiv) in toluene were heated in a microwave at 85 °C for 30 min. The resulting mixture was neutralized to pH 7 with a saturated solution of NaHCO₃ and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO₄ and concentrated under vacuum. The crude product was purified by flash chromatography on silica gel.

6-Isobutyl-quinazolin-4(3H)-one (1d)

General Method A was used with (2-methylpropyl)boronic acid (183 mg, 1.50 mmol, 1.2 equiv). The residue was purified with silica gel chromatography (PE/EtOAc, 1:1) to afford N ³-benzyl-6-isobutylquinazolin-4(3H)-one (230 mg, 62%) as a white solid; mp 95.5 °C.

¹H NMR (300 MHz, CDCl₃): δ = 8.09 (d, J = 2.1 Hz, 1 H, H₅), 8.07 (s, 1 H, H₁), 7.62 (d, J = 8.3 Hz, 1 H, H₈), 7.54 (dd, J = 8.3, 2.1 Hz, 1 H, H₇), 7.38–7.27 (m, 5 H, H_Ph), 5.20 (s, 2 H, CH₂), 2.61 (d, J = 7.2 Hz, 2 H, CH₂, H₉), 1.93 (hept, J = 13.3, 6.7 Hz, 1 H, CH, H₁₀), 0.91 (d, J = 6.6 Hz, 6 H, CH₃, H₁₁).

¹³C NMR (75 MHz, CDCl₃): δ = 161.32 (C₄), 146.35 (Cq), 145.72 (C₂), 141.65 (Cq), 135.97 (Cq), 135.82 (C₇), 129.12 (C_Ph), 128.38 (C_Ph), 128.13 (C_Ph), 127.32 (C₈), 126.60 (C₅), 49.67 (CH₂), 45.21 (CH₂), 30.36 (CH), 22.41 (C₁₁).

IR (neat): 2952, 1660, 1606, 1490, 1368, 747, 719, 697 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₉H₂₁N₂O: 293.1654; found: 293.1662.

General Method B was used with N ³-benzyl-6-isobutylquinazolin-4(3H)-one (210 mg, 0.72 mmol, 1 equiv) and AlCl₃ (527 mg, 3.95 mmol, 5.5 equiv) in toluene (4 mL). The crude material was purified with silica gel chromatography (DCM/MeOH, 95:5) to afford 1d (120 mg, 82%) as a white solid; mp 184.5 °C.

¹H NMR (300 MHz, CDCl₃): δ = 12.24 (s, 1 H, H_N–H), 8.13 (s, 1 H, H₂), 8.07 (d, J = 2.0 Hz, 1 H, H₅), 7.70 (d, J = 8.3 Hz, 1 H, H₈), 7.61 (dd, J = 8.3, 2.0 Hz, 1 H, H₇), 2.64 (d, J = 7.2 Hz, 2 H, H₉), 1.95 (n, 6.7 Hz, 1 H, H₁₀), 0.93 (d, J = 6.6 Hz, 6 H, H₁₁).

¹³C NMR (75 MHz, CDCl₃): δ = 163.83 (C₄), 147.39 (Cq), 142.96 (C₂), 141.73 (Cq), 136.53 (C₇), 127.64 (C₈), 125.96 (C₅), 122.15 (Cq), 45.22 (C₁₀), 30.41 (C₉), 22.42 (C₁₁).

IR (neat): 3131, 2951, 2866, 1689, 1655, 1610, 1485, 1254, 1164, 923, 847, 549, 487 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₂H₁₅N₂O: 203.1184; found: 203.1193.

6-(4-Cyanophenyl)quinazolin-4(3H)-one (1f)

General Method A was used with 4-cyanophenylboronic acid (220 mg, 1.50 mmol, 1.2 equiv). The residue was purified with silica gel chromatography (DCM/EtOAc, 6:4) to afford N ³-benzyl-6-(4-cyano-phenyl)quinazolin-4(3H)-one (342 mg, 80%) as a white solid; mp 204.4 °C.

¹H NMR (300 MHz, CDCl₃): δ = 8.55 (d, J = 2.1 Hz, 1 H, H₅), 8.15 (s, 1 H, H₂), 7.98 (dd, J = 8.5, 2.2 Hz, 1 H, H₇), 7.81 (d, J = 8.4 Hz, 1 H, H₈), 7.77 (s, 4 H, H_10,11), 7.42–7.28 (m, 5 H, H_15,16,17), 5.23 (s, 2 H, H₁₃).

¹³C NMR (75 MHz, CDCl₃): δ = 161.05 (C₄), 148.25 (Cq), 147.02 (C₂), 144.01 (Cq), 138.16 (Cq), 135.64 (Cq), 133.03 (C₇), 132.93 (C_{10 or 11}), 129.22 (C_{15 or 16}), 128.68 (C₁₇), 128.58 (C₈), 128.19 (C_{15 or 16}), 127.91 (C_{10 or 11}), 125.53 (C₅), 122.77 (Cq), 118.80 (Cq), 111.75 (Cq), 49.91 (C₁₃).

IR (neat): 3049, 2946, 2229, 1686, 1602, 1482, 1368, 830, 752, 723, 701 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₂₂H₁₆N₃O: 338.1293; found: 338.1298.

General Method B was used with N ³-benzyl-6-(4-cyanophenyl)quinazolin-4(3H)-one (320 mg, 0.95 mmol, 1 equiv) and AlCl₃ (507 mg, 3.80 mmol, 4 equiv) in toluene (5 mL). The crude material was purified with silica gel chromatography (DCM/MeOH, 95:5) to afford 6-(4-cyanophenyl)quinazolin-4(3H)-one (1f) (84 mg, 34%) as a white solid; mp 272.9 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.38 (s, 1 H, H_N–H), 8.41 (dd, J = 2.3, 0.5 Hz, 1 H, H₅), 8.20 (dd, J = 8.6, 2.3 Hz, 1 H, H₇), 8.15 (s, 1 H, H₂), 8.03–7.93 (m, 4 H, H_10,11), 7.79 (d, J = 8.6 Hz, 1 H, H₈).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 160.63 (C₄), 148.90 (Cq), 146.08 (C₂), 143.24 (Cq), 136.40 (Cq), 133.01 (C_{10 or 11}), 132.95 (C₇), 128.23 (C₈), 127.76 (C_{10 or 11}), 124.04 (C₅), 123.06 (Cq), 118.76 (Cq), 110.47 (Cq).

IR (neat): 3170, 2921, 2236, 1676, 1607, 1486, 916, 824, 549, 525 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₅H₁₀N₃O: 248.0824; found: 248.0836.

C–H Perfluoroalkylation of Quinazolinone Derivatives 1 or 5; General Procedure C

In a sealed microwave vial, quinazolinone 1 or 9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile 5 (0.42 mmol, 1.0 equiv), K₂CO_3­ (118 mg, 0.84 mmol, 2.0 equiv) and perfluoroalkyl iodide (1.27 mmol, 3.0 equiv) were added sequentially under Ar and then dissolved in anhydrous DMSO (3 mL). The reaction mixture was stirred at 50 °C and irradiated with blue LEDs at 425 nm for 24 h. The resulting mixture was extracted with DCM. The organic layer was washed with brine, dried over MgSO₄, and concentrated under vacuum. The crude product was purified by flash chromatography on silica gel.

8-Perfluorohexylquinazolin-4(3H)-one (2a), 5,8-Bisperfluorohexyl­quinazolin-4(3H)-one (3a), and 6,8-bisperfluorohexylquinazolin-4(3H)-one (4a)

General Method C was used with quinazolin-4(3H)-one 1a (61 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 9:1) to afford 2a (64 mg, 33%) as a white solid; mp 185.2 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.61 (s, 1 H, H_N–H), 8.45 (dd, J = 8.0, 1.5 Hz, 1 H, H₅), 8.25 (s, 1 H, H₂), 8.12 (dd, J = 7.8, 1.7 Hz, 1 H, H₇), 7.70 (t, J = 7.9 Hz, 1 H, H₆).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 159.92 (C₄), 147.19 (t, J = 1.1 Hz, C_8a), 146.45 (C₂), 134.37 (t, J = 9.1 Hz, C₇), 131.22 (C₅), 126.29 (C₆), 124.09 (C_4a), 123.46 (t, J = 21.1 Hz, C₈), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –75.67 (t, J = 10.0 Hz), –99.08 to –99.40 (m), –114.38 to –114.72 (m), –116.66 to –116.95 (m), –117.63 to –118.04 (m), –121.01 to –121.35 (m).

IR (neat): 1690, 1655, 1620, 1237, 1195, 1142, 1121, 1099, 1080, 808, 775, 733, 666, 534, 493 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₄H₆F₁₃N₂O: 465.0273; found: 465.0272.

Compound 3a (44 mg, 13%) was obtained as a yellowish solid; mp 146.4 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.62 (s, 1 H, H_N–H), 8.39 (d, J = 8.3 Hz, 1 H, H₇), 8.35 (s, 1 H, H₂), 8.12 (d, J = 8.3 Hz, 1 H, H₆).

¹³C NMR (75 MHz, acetone-d ₆): δ = 157.89 (C₄), 151.12 (Cq), 147.42 (C₂), 134.82 (t, J = 9.6 Hz, C₇), 133.53 (t, J = 24.2 Hz, Cq), 130.80 (t, J = 22.0 Hz, Cq), 127.95 (t, J = 12.3 Hz, C₆), 124.47 (Cq), 122.08–119.29 (m, Cq), 118.14–114.75 (m, Cq), 113.53–110.84 (m, Cq), 110.66–107.53 (m, Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.72 (t, J = 10.2 Hz), –97.73 (tt, J = 15.2, 3.7 Hz), –105.02 – –105.25 (m), –115.50 to –115.75 (m), –119.01 to –119.24 (m), –122.07 to –122.38 (m), –122.97 to –123.33 (m), –126.65 to –126.91 (m).

IR (neat): 3048, 2950, 1693, 1634, 1237, 1197, 1138, 1119, 820, 809, 765, 713, 685, 623, 534, 482 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₀H₃F₂₆N₂O: 780.9830; found: 780.9808.

Compound 4a (64 mg, 19%) was obtained as a white solid; mp 197.1 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.76 (s, 1 H, H_N–H), 8.74 (d, J = 2.2 Hz, 1 H, H₅), 8.43 (s, 1 H, H₂), 8.29 (d, J = 2.3 Hz, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.93 (C₄), 151.76 (Cq), 149.18 (C₂), 133.79–131.73 (m, C₇), 131.25 (C₅), 128.25–125.31 (m, Cq), 126.40 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.49 to –81.88 (m), –105.29 to –105.72 (m), –110.75 to –111.17 (m), –119.80 to –120.23 (m), –121.69 to –122.42 (m), –123.13 to –123.42 (m), –123.27 to –123.56 (m), –126.56 to –127.01 (m).

IR (neat): 1688, 1618, 1256, 1237, 1196, 1141, 1101, 916, 723, 710, 664, 533 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₀H₃F₂₆N₂O: 780.9830; found: 780.9849.

5-Methyl-8-perfluorohexylquinazolin-4(3H)-one (2b) and 5-Methyl-6,8-bisperfluorohexylquinazolin-4(3H)-one (4b)

General Method C was used with 5-methylquinazolin-4(3H)-one 1b (67 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2b (78 mg, 39%) as a white solid; mp 148.7 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.41 (s, 1 H, H_NH), 8.16 (s, 1 H, H₂), 7.94 (d, J = 8.0 Hz, 1 H, H₇), 7.45 (dd, J = 8.0, 1.0 Hz, 1 H, H₆), 2.84 (s, 3 H, CH₃).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 160.83 (C₄), 148.83 (C_8a), 146.35 (Cq), 146.03 (C₂), 133.31 (t, J = 9.6 Hz, C₇), 128.54 (C₆), 122.29 (Cq), 121.78–121.37 (m, C₈), 121.00–105.00 (m, C_CF), 23.12 (C_Me).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.23 (tt, J = 9.7, 2.8 Hz), –103.61 (tt, J = 15.1, 3.5 Hz), –118.78 to –119.14 (m), –121.46, –122.24 to –122.65 (m), –122.44, –125.58 to –125.95 (m).

IR (neat): 3180, 3053, 2944, 1669, 1632, 1593, 1246, 1215, 1196, 1138, 1118, 1096, 722, 697, 545, 509 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₅H₈N₂OF₁₃: 479.0429; found: 479.0421.

Compound 4b (68 mg, 22%) was obtained as a white solid; mp 170.7 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.57 (s, 1 H, H_N–H), 8.34 (s, 1 H, H₇), 8.12 (s, 1 H, H₂), 2.79 (s, 3 H, CH₃).

¹³C NMR (75 MHz, acetone-d ₆): δ = 161.22 (C₄), 148.66 (C₂), 144.40–143.29 (m, Cq), 133.36–132.29 (m, C₇), 125.59 (Cq), 126.92–123.55 (m, Cq), 123.00–105.00 (m, C_CF), 19.59 (CH₃). Two carbons are missing due to overlap.

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.51 to –81.87 (m), –103.46 to –103.85 (m), –105.11 to –105.50 (m), –119.51 to –119.85 (m), –120.53 to –120.88 (m), –122.00 to –122.26 (m), –123.01 to –123.43 (m), –126.54 to –126.98 (m).

IR (neat): 1674, 1633, 1596, 1246, 1197, 1143, 1097, 723, 544 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₁H₅F₂₆N₂O: 794.9987; found: 794.9978.

6-Methyl-8-perfluorohexylquinazolin-4(3H)-one (2c)

General Method C was used with 6-methylquinazolin-4(3H)-one 1c (67 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2c (62 mg, 31%) as a white solid; mp 194.5 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.53 (s, 1 H, H_N–H), 8.25 (d, J = 2.1, Hz, 1 H, H₅), 8.19 (s, 1 H, H₂), 7.96 (d, J = 2.1 Hz, 1 H, H₇), 2.52 (s, 3 H, CH₃).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 159.88 (C₄), 145.60 (C₂), 145.12 (Cq), 136.40 (Cq), 135.33 (t, J = 8.7 Hz, C₇), 130.64 (C₅), 123.93 (Cq), 123.79–122.76 (m, Cq), 123.00–105.00 (m, C_CF), 20.53 (C_Me).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.28 (t, J = 9.7, 2.9 Hz), –103.93 (t, J = 17.4 Hz), –119.02 to –119.32 (m), –121.38 to –121.66 (m), –122.37 to –122.70 (m), –125.69 to –125.98 (m).

IR (neat): 3182, 3060, 2926, 1678, 1614, 1240, 1205, 1175, 1144, 808, 693, 658, 514 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₅H₈F₁₃N₂O: 479.0429; found: 479.0429.

6-Isobutyl-8-perfluorohexylquinazolin-4(3H)-one (2d)

General Method C was used with 6-(2-methylpropyl)quinazolin-4(3H)-one 1d (85 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (PE/EtOAc, 6:4) to afford 2d (103 mg, 47%) as a white solid; mp 185.4 °C.

¹H NMR (300 MHz, CDCl₃): δ = 10.89 (s, 1 H, H_N–H), 8.33 (d, J = 2.1 Hz, 1 H, H₅), 8.12 (d, J = 2.0 Hz, 1 H, H₂), 7.86 (d, J = 2.1 Hz, 1 H, H₇), 2.69 (d, J = 7.2 Hz, 2 H, H₉), 1.97 (n, J = 6.7 Hz, 1 H, H₁₀), 0.95 (d, J = 6.6 Hz, 6 H, H₁₁).

¹³C NMR (75 MHz, CDCl₃): δ = 161.92 (C₄), 145.63 (Cq), 142.81 (C₂), 141.13 (Cq), 136.48 (t, J = 8.6 Hz, C₇), 130.82 (C₅), 124.29–123.95 (m, Cq), 123.90 (Cq), 123.00–105.00 (m, C_CF), 44.98 (C₁₀), 30.39 (C₉), 22.25 (C₁₁).

¹⁹F NMR (282 MHz, CDCl₃): δ = –80.75 (tt, J = 10.2, 2.6 Hz), –105.07 to –105.47 (m), –119.64 to –120.04 (m), –121.42 to –121.68 (m), –122.53 to –122.80 (m), –122.46 to –122.87 (m), –125.92 to –126.31 (m).

IR (neat): 2969.7, 2878.8, 1677, 1620, 1236, 1194, 1143, 1044, 912, 876, 720, 556 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₈H₁₂F₁₃N₂O: 519.0742; found: 519.0765.

6-Phenyl-8-perfluorohexylquinazolin-4(3H)-one (2e)

General Method C was used with 6-phenylquinazolin-4(3H)-one (93 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 9:1) to afford 2e (102 mg, 45%) as a white solid; mp 146.5 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.45 (s, 1 H, H_N–H), 8.72 (d, J = 2.3 Hz, 1 H, H₅), 8.38 (d, J = 2.3 Hz, 1 H, H₇), 8.27 (s, 1 H, H₂), 7.88–7.81 (m, 2 H, H₁₀), 7.61–7.52 (m, 2 H, H₁₁), 7.52–7.45 (m, 1 H, H₁₂).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.61 (C₄), 147.56 (Cq), 146.43 (C₂), 139.73 (Cq), 139.07 (Cq), 133.56 (t, J = 9.0 Hz, C₇), 130.20 (C₁₁), 129.46 (C₁₂), 129.41 (C₅), 128.05 (C₁₀), 126.31 (t, J = 21.8 Hz, Cq), 126.15 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.67 (tt), –104.84 to –105.13 (m), –119.62 to –119.92 (m), –122.03 to –122.29 (m), –123.07 to –123.40 (m), –126.60 to –126.91 (m).

IR (neat): 3034, 1678, 16618, 1233, 1199, 1142, 1122, 808, 699, 663, 548 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₂₀H₁₀F₁₃N₂O: 541.0586; found: 541.0859.

6-(4-Cyanophenyl)-8-perfluorohexylquinazolin-4(3H)-one (2f)

General Method C was used with 6-(4-cyanophenyl)quinazolin-4(3H)-one (103 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (PE/EtOAc, 6:4) to afford 2f (98 mg, 41%) as a white solid; mp 237.8 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.49 (s, 1 H, H_N–H), 8.78 (d, J = 2.3 Hz, 1 H, H₅), 8.46 (d, J = 2.3 Hz, 1 H, H₇), 8.30 (d, J = 2.8 Hz, 1 H, H₂), 8.17–8.07 (m, 2 H, H_10or11), 8.03–7.94 (m, 2 H, H_10or11).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.48 (C₄), 148.41 (Cq), 147.07 (C₂), 143.42 (Cq), 137.78 (Cq), 133.90 (C_10or11), 133.69 (t, J = 9.9 Hz, C₇), 130.22 (C₅), 129.13 (C_10or11), 127.02–126.29 (m, Cq), 126.30 (Cq), 123.00–105.00 (m, C_CF), 119.12 (Cq), 112.98 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.66 (tt, J = 10.1, 2.7 Hz), –104.75 to –105.23 (m), –119.41 to –119.89 (m), –121.96 to –122.28 (m), –122.95 to –123.46 (m), –123.05 to –123.37 (m), –126.48 to –126.96 (m).

IR (neat): 3073, 2226, 1699, 1607, 1472, 1199, 1143, 808, 705, 529 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₁H₇F₁₃N₃O: 564.0382; found: 564.0378.

6-Fluoro-8-perfluorohexylquinazolin-4(3H)-one (2g) and 6-Fluoro-5,8-bisperfluorohexylquinazolin-4(3H)-one (3g)

General Method C was used with 6-fluoroquinazolin-4(3H)-one (69 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2g (71 mg, 35%) as a white solid; mp 193.3 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.50 (s, 1 H, H_N–H), 8.24 (s, 1 H, H₂), 8.17 (dd, J = 7.9, 3.0, 1 H, H₅), 8.00 (dd, J = 8.9, 3.1 Hz, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.31 (d, J = 247.9 Hz, C₆), 159.94 (C₄), 145.94 (C₂), 145.28 (C_8a), 128.95–127.64 (m, C₈), 127.40 (d, J = 7.9 Hz, C_4a), 123.83 (dt, J = 27.4, 9.7 Hz, C₇), 123.00–105.00 (m, C_CF), 116.97 (d, J = 22.9 Hz, C₅).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.69 (tt, J = 10.2, 2.5 Hz), –105.06 to –105.27 (m), –113.68, –119.67 to –119.89 (m), –122.09 to –122.33 (m), –123.14 to –123.39 (m), –126.67 to –126.90 (m).

IR (neat): 3185, 3064, 2938, 1683, 1618, 1422, 1241, 1202, 1143, 862, 661, 537cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₄H₃F₁₄N₂O: 481.0022; found: 481.0027.

Compound 3g (41 mg, 12%) was obtained as a white solid; mp 158.7 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.67 (s, 1 H, H_N–H), 8.36–8.31 (m, 1 H, H₂), 8.26 (d, J = 12.4 Hz, 2 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.91 (dt, J = 252.3, 5.2 Hz, C₆), 157.63 (d, J = 3.8 Hz, C₄), 147.42 (Cq), 146.79 (C₂), 133.10 (d, J = 7.3 Hz, Cq), 126.29–125.29 (m, C_5,7,8),, 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.45 to –81.86 (m), –96.50 (dt, J = 43.3, 14.9 Hz), –104.76 – –105.42 (m), –105.49 to –106.03 (m), –115.77 to –116.15 (m), –118.70 to –119.15 (m), –122.03 to –122.62 (m), –122.89 to –123.45 (m), –123.01 to –123.34 (m), –126.49 to –127.01 (m).

IR (neat): 2933, 1697, 1628, 1401, 1232, 1200, 1142, 1121, 1103, 1057, 731, 531 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₀H₂F₂₇N₂O: 798.9736; found: 798.9760.

6-Chloro-8-perfluorohexylquinazolin-4(3H)-one (2h)

General Method C was used with 6-chloroquinazolin-4(3H)-one 1h (76 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2h (85 mg, 41%) as a white solid (mp 220.6 °C) and 3a (50 mg, 15%) as a yellowish solid.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.79 (s, 1 H, H_N–H), 8.39 (d, J = 2.5 Hz, 1 H, H₅), 8.29 (d, J = 3.7 Hz, 1 H, H₂), 8.17 (d, J = 2.5 Hz, 1 H, H₇).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 159.02 (C₄), 146.99 (C₂), 146.00 (Cq), 134.20 (t, J = 9.3 Hz, C₇), 130.63 (C₅), 130.33 (Cq), 125.65 (Cq), 126.52–124.86 (m, Cq),, 123.00–105.00 (m, C_CF).

¹⁹ F NMR (282 MHz, DMSO-d ₆): δ = –80.27 (t, J = 9.8 Hz), –104.00 to –104.39 (m), –118.83 to –119.24 (m), –121.35 to –121.70 (m), –122.33 to –122.69 (m), –125.63 to –126.03 (m).

IR (neat): 1682, 1613, 1224, 1203, 1173, 1147, 1089, 807, 654, 518 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₄H₅ ³⁵ClF₁₃N₂O: 498.9876; found: 498.9891.

6-Bromo-8-perfluorohexylquinazolin-4(3H)-one (2i)

General Method C was used with 6-bromoquinazolin-4(3H)-one 1i (91 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2i (49 mg, 21%) a white solid (mp 191.6 °C) and 3a (40 mg, 12%) as a yellowish solid.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.80 (s, 1 H, H_N–H), 8.52 (d, J = 2.3 Hz, 1 H, H₅), 8.30 (d, J = 3.7 Hz, 1 H, H₂), 8.25 (d, J = 2.4 Hz, 1 H, H₇).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 158.90 (C₄), 147.11 (C₂), 146.31 (Cq), 137.28–136.08 (m, C₇), 133.48 (C₅), 125.87 (Cq), 118.44 (Cq), 123.00–105.00 (m, C_CF), 119.35–117.56 (m, Cq).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.22 (tt, J = 9.8, 4.9 Hz), –103.85 to –104.37 (m), –118.72 to –119.23 (m), –121.28 to –121.66 (m), –122.28 to –122.66 (m), –125.53 to –126.03 (m).

IR (neat): 3176, 2926, 1680, 1616, 1238, 1198, 1142, 1128, 845, 769, 745, 509 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₄H₅BrF₁₃N₂O: 542.9378; found: 542.9376.

6-Iodo-8-perfluorohexylquinazolin-4(3H)-one (2j)

General Method C was used with 6-iodoquinazolin-4(3H)-one 1j (114 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2j (68 mg, 27%) as a white solid (mp 197.7 °C) and 3a (27 mg, 8%) as a yellowish solid.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.76 (d, J = 3.6 Hz, 1 H, H_N–H), 8.68 (d, J = 2.1 Hz, 1 H, H₅), 8.31 (d, J = 2.1 Hz, 1 H, H₇), 8.29 (d, J = 3.7 Hz, 1 H, H₂).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 158.70 (C₄), 147.07 (C₂), 146.55 (Cq), 142.62–140.98 (m, C₇), 139.54 (C₆), 125.79 (Cq), 125.60–125.03 (m, Cq), 123.00–105.00 (m, C_CF), 90.81 (Cq).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.28 (t, J = 9.7 Hz), –103.97 to –104.39 (m), –118.85 to –119.26 (m), –121.38 to –121.66 (m), –122.32 to –122.72 (m), –125.63 to –126.04 (m).

IR (neat): 1681, 1618, 1193, 1141, 907, 806, 733, 695, 647, 504 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₄H₅F₁₃IN₂O: 590.9239; found: 590.9241.

6-Nitro-8-perfluorohexylquinazolin-4(3H)-one (2k)

General Method C was used with 6-nitroquinazolin-4(3H)-one 1k (80 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2k (32 mg, 15%) as a white solid; mp 228.6 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 13.13 (s, 1 H, H_N–H), 9.03 (d, J = 2.7 Hz, 1 H, H₅), 8.67 (d, J = 2.7 Hz, 1 H, H₇), 8.48 (s, 1 H, H₂).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 159.32 (C₄), 151.33 (Cq), 149.95 (C₂), 144.08 (Cq), 128.16 (t, J = 8.9 Hz, C₇), 126.57 (C₅), 125.28–124.44 (m, Cq), 124.80 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.29 (t, J = 10.0 Hz), –104.38 to –104.74 (m), –118.66 to –119.06 (m), –121.46, –122.28 to –122.68 (m), –125.62 to –125.99 (m).

IR (neat): 1717, 1687, 1614, 1341, 1193, 1145, 655, 501 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₄H₃F₁₃N₃O₃: 507.9967; found: 507.9959.

6,7-Difluoro-8-perfluorohexylquinazolin-4(3H)-one (2l) and 6,7-difluoro-5,8-bisperfluorohexyl-quinazolin-4(3H)-one (3l)

General Method C was used with 6,7-difluoroquinazolin-4(3H)-one 1l (76 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2l (65 mg, 31%) as a white solid; mp 165.3 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.59 (s, 1 H, H_N–H), 8.36 (t, J = 9.1 Hz, 1 H, H₅), 8.28 (s,1 H, H₂).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.44 (C₄), 155.77 (dd, J = 266.4, 19.7 Hz, Cq), 150.08 (dd, J = 250.8, 15.1 Hz, Cq), 147.14 (C₂), 146.85–146.21 (m, Cq), 122.57–121.48 (m, Cq), 119.05 (dd, J = 18.9, 3.4 Hz, C₅), 118.93–114.64 (m, Cq), 119.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –80.19 (tt, J = 9.9, 2.7 Hz), –101.99 to –102.62 (m), –120.33 to –120.71 (m), –121.51 to –121.90 (m), –122.24 to –122.63 (m), –124.40 to –124.96 (m), –125.47 to –125.98 (m), –135.49, –135.57.

IR (neat): 3054, 2913, 1683, 1618, 1464, 1241, 1197, 1145, 1126, 804, 666, 652, 527 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₄H₂F₁₅N₂O: 498.9928; found: 498.9934.

Compound 3l (24 mg, 13%) was obtained as a white solid; mp 159.9 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.73 (s, 1 H, H_N–H), 8.35 (d, J = 2.4 Hz, 1 H, H₂).

¹³C NMR (75 MHz, acetone-d ₆): δ = 157.11 (d, J = 15.3 Hz, C₄), 155.38 (dd, J = 263.6, 4.4 Hz, Cq), 150.58 (dd, J = 253.0, 4.6 Hz, Cq), 148.32 (Cq), 147.54 (C₂), 121.72 (Cq), 120.75 (d, J = 3.6 Hz, Cq), 120.03 (Cq), 120.0–104.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.68 (t, J = 10.1 Hz), –96.39 to –96.88 (m), –102.94 to –103.41 (m), –115.75 to –116.09 (m), –120.33 to –120.69 (m), –121.36 to –121.93 (m), –122.28 to –122.59 (m), –122.98 to –123.35 (m), –126.55 to –126.92 (m), –129.68 to –130.24 (m).

IR (neat): 1695, 1632, 1465, 1236, 1197, 1160, 1075, 959, 720, 711, 656, 528 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₀H₂F₂₈N₂O: 816.9642; found: 816.9643.

6,7-Dimethoxy-8-perfluorohexylquinazolin-4(3H)-one (2m) and 6,7-Dimethoxy-5,8-bisperfluorohexyl-quinazolin-4(3H)-one (3m)

General Method C was used with 6,7-dimethoxyquinazolin-4(3H)-one 1m (87 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 95:5) to afford 2m (49 mg, 23%) as a white solid; mp 123.4 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.25 (s, 1 H, H_N–H), 8.08 (s, 1 H, H₂), 7.92 (s, 1 H, H₅), 4.07 (s, 3 H, OCH₃), 3.98 (s, 3 H, OCH₃).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.22 (C₄), 156.90 (Cq), 153.56 (Cq), 143.99 (C₂), 143.81 (Cq), 121.21 (Cq), 111.77 (C₅), 123.00–105.00 (m, C_CF), 62.44 (Cq), 56.77 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.68 (t, J = 10.1 Hz), –100.81 to –101.39 (m), –119.97 to –120.56 (m), –122.25 to –122.79 (m), –122.99 to –123.46 (m), –126.46 to –127.13 (m).

IR (neat): 3029, 2926, 1668, 1471, 1236, 1202, 1142, 1122, 1030, 714, 653, 548 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₆H₁₀F₁₃N₂O₃: 525.0484; found: 525.0460.

Compound 3m (21 mg, 6%) was obtained as a white solid; mp 124.1 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.36 (s, 1 H, H_N–H), 8.13 (s, 1 H, H₂), 4.01 (s, 3 H, H_OMe), 3.96 (s, 3 H, H_OMe).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.46 (C₄), 158.18 (Cq), 154.49 (Cq), 147.85 (Cq), 145.92 (C₂), 133.35 (Cq), 120.26 (Cq), 120.78–118.95 (m, Cq), 121.00–105.00 (m, C_CF), 62.47 (s, Cq), 62.35 (s, Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.05 to –82.07 (m), –95.01 (t, J = 14.5, 3.7 Hz), –101.08 (t, J = 15.2, 11.4, 7.7 Hz), –114.15, –119.33 to –120.27 (m), –121.78 to –123.59 (m), –126.17 to –127.17 (m), –126.80.

IR (neat): 3187, 2919, 2847, 1688, 1676, 1629, 1401, 1236, 1200, 1141, 1200, 1072, 1012, 708, 647 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₂H₇F₂₆N₂O₃: 841.0042; found: 841.0060.

8-Perfluoropropylquinazolin-4(3H)-one (2aa), 5,8-Bisperfluoro-propylquinazolin-4(3H)-one (3aa), 6,8-Bisperfluoropropyl-quinazolin-4(3H)-one (4aa)

General Method C was used with quinazolin-4(3H)-one 1a (61 mg) and perfluoropropyl iodide (0.22 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 9:1) to afford 2aa (42 mg, 31%) as a white solid; mp 181.1 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.36 (s, 1 H, H_N–H), 8.52 (dd, J = 7.9, 1.5 Hz, 1 H, H₅), 8.24 (s, 1 H, H₂), 8.14 (dd, J = 7.7, 1.6 Hz, 1 H, H₇), 7.79–7.68 (m, 1 H, H₆).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.59 (C₄), 148.42 (C_8a), 146.45 (C₂), 135.07 (t, J = 9.1 Hz, C₇), 132.05 (C₅), 127.13 (C₆), 125.58 (C_4a), 125.43 (t, J = 21.8 Hz, C₈), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.09 (t, J = 10.1 Hz), –105.72 to –105.86 (m), –124.58 to –124.62 (m).

IR (neat): 3084, 1692, 1621, 1238, 1198, 1144, 775, 668 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₁H₆F₇N₂O: 315.0368; found: 315.0363.

Compound 3aa (34 mg, 17%) was obtained as a white solid; mp 125.6 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.66 (s, 1 H, H_N–H), 8.38 (d, J = 8.3 Hz, 1 H, H₇), 8.36 (s, 1 H, H₂), 8.10 (d, J = 8.3 Hz, 1 H, H₆).

¹³C NMR (75 MHz, acetone-d ₆): δ = 157.93 (C₄), 150.98 (Cq), 147.42 (C₂), 134.68 (t, J = 9.6 Hz, C₇), 133.38 (t, J = 24.5 Hz, C₅), 130.42 (t, J = 24.3 Hz, C₈), 127.65 (t, J = 12.3 Hz, C₆), 124.29, 121.82–119.23 (m), 118.34–115.68 (m), 115.52–111.82 (m), 111.68–108.86 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.20 (t, J = 10.1 Hz), –81.40 (t, J = 9.9 Hz), –98.13 to –98.31 (m), –105.92 to –106.08 (m), –119.64 to –119.70 (m), –123.72 to –123.77 (m).

IR (neat): 3059, 2938, 1692, 1632, 1349, 1198, 1117, 895, 842, 746 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₄H₅F₁₄N₂O: 483.0178; found: 483.0180.

Compound 4aa (51 mg, 25%) was obtained as a white solid; mp 198.6 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.75 (s, 1 H, H_N–H), 8.72 (d, J = 2.2 Hz, 1 H, H₅), 8.43 (s, 1 H, H₂), 8.25 (d, J = 2.2 Hz, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.94 (C₄), 151.27 (Cq), 149.22 (C₂), 132.14 (t, J = 6.5 Hz, C₇), 131.13 (t, J = 6.8 Hz, C₅), 127.00 (t, J = 22.4 Hz, C₆), 126.37 (Cq), 126.19 (t, J = 25.6 Hz, C₈), 122.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –80.80 (t, J = 9.8 Hz), –81.09 (t, J = 9.9 Hz), –106.32 to –106.47 (m), –111.96 to –112.11 (m), –124.58 to –124.62 (m), –126.80 to –126.84 (m).

IR (neat): 3061, 2940, 1688, 1617, 1352, 1258, 1218, 1180, 1119, 906, 749 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₄H₅F₁₄N₂O: 483.0178; found: 483.0175.

8-Perfluorobutylquinazolin-4(3H)-one (2ab), 5,8-Bisperfluorobutylquinazolin-4(3H)-one (3ab), 6,8-Bisperfluorobutylquinazolin-4(3H)-one (4ab)

General Method C was used with quinazolin-4(3H)-one 1a (61 mg) and perfluorobutyl iodide (0.22 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 9:1) to afford 2ab (47 mg, 31%) as a white solid; mp 180.8 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.61 (s, 1 H, H_N–H), 8.45 (dd, J = 8.0, 1.5 Hz, 1 H, H₅), 8.26 (s, 1 H, H₂), 8.13 (dd, J = 7.7, 1.6 Hz, 1 H, H₇), 7.70 (t, J = 7.8, 0.9 Hz, 1 H, H₆).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 159.92 (C₄), 147.19 (C_8a), 146.46 (C₂), 134.40 (t, J = 8.9 Hz, C₇), 131.24 (C₅), 126.31 (C₆), 124.09 (C_4a), 123.36 (t, J = 21.6 Hz, C₈), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.43 (tt, J = 9.8, 3.0 Hz), –101.08 to –107.36 (m), –116.42 – –121.79 (m), –123.67 to –126.95 (m).

IR (neat): 1683, 1618, 1233, 1190, 1135, 856, 776, 693 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₂H₆F₉N₂O: 365.0336; found: 365.0352.

Compound 3ab (24 mg, 10%) was obtained as a white solid; mp 139.9 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.66 (s, 1 H, H_N–H), 8.39 (d, J = 8.2 Hz, 1 H, H₇), 8.35 (d, J = 2.6 Hz, 1 H, H₂), 8.12 (d, J = 8.3 Hz, 1 H, H₆).

¹³C NMR (75 MHz, acetone-d ₆): δ = 157.84 (C₄), 151.07 (Cq), 147.42 (C₂), 134.74 (t, J = 9.3 Hz, C₇), 133.72–132.56 (m), 130.91–130.07 (m), 127.81 (t, J = 12.4 Hz, C₆), 124.41 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.62 (tt, J = 10.4, 2.5 Hz), –81.74 (tt, J = 10.2, 2.8 Hz),97.78 to –97.97 (m), –105.26 to –105.44 (m), –116.36 to –116.49 (m), –119.95 to –120.12 (m), –126.39 to –126.71 (m).

IR (neat): 3060, 2932, 2865, 1689, 1633, 1231, 1196, 1175, 1129, 864, 821, 734, 710 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₆H₅F₁₈N₂O: 583.0114; found: 583.0093.

Compound 4ab (29 mg, 12%) was obtained as a white solid; mp 188.8 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.78 (s, 1 H, H_N–H), 8.74 (d, J = 2.2 Hz, 1 H, H₅), 8.43 (s, 1 H, H₂), 8.28 (d, J = 2.2 Hz, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.92 (C₄), 151.34 (Cq), 149.24 (C₂), 132.74–132.09 (m, C₇), 131.83–130.78 (m, C₅), 128.36–125.55 (m, Cq), 126.40 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.74 to –81.96 (m), –105.65 to –105.82 (m), –111.12 to –111.26 (m), –120.78 to –120.91 (m), –122.99 to –123.09 (m), –126.02 to –126.17 (m), –126.36 to –126.53 (m).

IR (neat): 3060, 2938, 1688, 1619, 1230, 1206, 186, 1175, 1129, 879, 745 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₆H₅F₁₈N₂O: 583.0114; found: 583.0131.

8-Perfluoropentylquinazolin-4(3H)-one (2ac), 5,8-Bisperfluoropentylquinazolin-4(3H)-one (3ac), 6,8-Bisperfluoropentylquinazolin-4(3H)-one (4ac)

General Method C was used with quinazolin-4(3H)-one 1a (61 mg) and perfluoropentyl iodide (0.24 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 9:1) to afford 2ac (48 mg, 29%) as a white solid; mp186.3 °C.

¹H NMR (300 MHz, DMSO-d ₆): δ = 12.61 (s, 1 H, H_N–H), 8.45 (dd, J = 8.0, 1.5 Hz, 1 H, H₅), 8.26 (d, J = 3.4 Hz, 1 H, H₂), 8.14 (dd, J = 7.7, 1.6 Hz, 1 H, H₇), 7.71 (t, J = 7.8, 1 H, H₆).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 159.91 (C₄), 147.18 (C_8a), 146.48 (C₂), 134.41 (t, J = 9.0 Hz, C₇), 131.24 (C₅), 126.33 (C₆), 124.08 (C_4a), 123.41 (t, J = 21.7 Hz, C₈), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –80.28 (tt, J = 9.7, 3.0 Hz), –103.78 to –104.01 (m), –119.28 to –119.51 (m), –122.09 to –122.34 (m), –125.60 to –125.83 (m).

IR (neat): 3084, 2901, 1691, 16256, 1620, 1237, 1193, 1139, 773, 693, 535, 493 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₃H₄F₁₁N₂O: 413.0148; found: 413.0142.

Compound 3ac (31 mg, 11%) was obtained as a white solid; mp 118.2 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.62 (s, 1 H, H_N–H), 8.39 (d, J = 8.4 Hz, 1 H, H₇), 8.35 (s, 1 H, H₂), 8.12 (d, J = 8.3 Hz, 1 H, H₆).

¹³C NMR (75 MHz, DMSO-d ₆): δ = 157.80 (C₄), 151.07 (Cq), 147.38 (C₂), 134.80 (t, J = 9.8 Hz, C₇), 134.05–131.79 (m, Cq), 131.64–128.41 (m, Cq), 128.41–127.26 (m, C₆), 124.42 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, DMSO-d ₆): δ = –81.16 to –81.37 (m), –97.13 to –97.38 (m), –104.59 to –104.83 (m), –115.25 to –115.36 (m), –115.18 to –115.44 (m), –118.73 to –119.00 (m), –122.41 to –122.75 (m), –125.96 to –126.33 (m).

IR (neat): 2925, 2854, 1692, 1632, 1596, 1231, 1188, 1134, 1098, 1082, 778, 722, 645, 575 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₈H₃F₂₂N₂O: 680.9894; found: 680.9905.

Compound 4ac (42 mg, 15%) was obtained as a white solid; mp 184.2 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.76 (s, 1 H, H_N–H), 8.74 (d, J = 2.2 Hz, 1 H H₅), 8.43 (s, 1 H H₂), 8.29 (d, J = 2.2 Hz, 1 H H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.94 (C₄), 151.35 (Cq), 149.29 (C₂), 132.69–132.08 (m, C₇), 131.28 (t, J = 6.8 Hz, C₅), 128.76–125.48 (m, Cq), 126.43 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.74 (t, J = 9.9, 2.8 Hz), –105.45 to –105.66 (m), –110.91 to –111.11 (m), –120.07 to –120.30 (m), –122.32 to –122.53 (m), –122.55 to –122.81 (m), –122.86 to –123.10 (m), –126.63 to –126.96 (m).

IR (neat): 2893, 1687, 1619, 1228, 1201, 1139, 814, 737, 550 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₈H₃F₂₂N₂O: 680.9894; found: 680.9886.

8-Perfluorooctylquinazolin-4(3H)-one (2ad) and 5,8-Bisperfluorooctylquinazolin-4(3H)-one (3ad)

General Method C was used with quinazolin-4(3H)-one 1a (61 mg) and perfluorooctyl iodide (690 mg). The residue was purified with silica gel chromatography (DCM/EtOAc, 9:1) to afford 2ad (54 mg, 23%) as a white solid; mp 182.9 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.35 (s, 1 H, H_N–H), 8.53 (dd, J = 8.0, 1.5 Hz, 1 H, H₅), 8.24 (s, 1 H, H₂), 8.17 (dd, J = 7.7, 1.6 Hz, 1 H, H₇), 7.80–7.70 (m, 1 H, H₆).

¹³C NMR (75 MHz, acetone-d ₆): δ = 160.54 (C₄), 148.51 (Cq), 146.50 (C₂), 136.55–133.66 (m, C₇), 132.10 (C₅), 127.13 (C₆), 125.66 (Cq), 125.32–124.94 (m, C₈), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.35 to –81.91 (m), –104.64 to –105.24 (m), –119.57 to –120.18 (m), –121.67 to –122.69 (m), –123.01 to –123.49 (m), –126.43 to –127.04 (m).

IR (neat): 3189, 3083, 2954, 1689, 1620, 1203, 1148, 918, 775, 657, 532 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₆H₆F₁₇N₂O: 565.0209; found: 565.0204.

Compound 3ad (20 mg, 8%) was obtained as a white solid; mp161.1 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 11.66 (s, 1 H, H_N–H), 8.40 (d, J = 8.3 Hz, 1 H, H₇), 8.36 (s, 1 H, H₂), 8.13 (d, J = 8.3 Hz, 1 H, H₆).

¹³C NMR (75 MHz, acetone-d ₆): δ = 157.82 (C₄), 151.11 (Cq), 147.39 (C₂), 135.58–134.11 (m, C₇), 134.11–132.77 (m, Cq), 132.01–129.69 (m, Cq), 128.31–127.59 (m, C₆), 124.44 (Cq), 123.00–105.00 (m, C_CF).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.64 (tt, J = 10.0, 2.6 Hz), –97.37 to –98.02 (m), –105.11 (t, J = 13.1 Hz), –115.20 to –115.90 (m), –118.72 to –119.39 (m), –121.64 to –122.71 (m), –122.86 to –123.47 (m), –122.99 to –123.52 (m), –126.40 to –127.08 (m).

IR (neat): 3201, 2936, 1695, 1631, 1199, 1146, 1114, 1085, 928, 658, 642, 560, 529 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₂₄H₃F₃₄N₂O: 980.9702; found: 980.9688.

6-Isobutyl-8-perfluorobutylquinazolin-4(3H)-one (2da)

General Method C was used with 6-(2-methylpropyl)quinazolin-4(3H)-one 1d (85 mg) and perfluorobutyl iodide (0.22 mL). The residue was purified with silica gel chromatography (PE/EtOAc, 3:2) to afford 2da (72 mg, 41%) as a white solid; mp 180.1 °C.

¹H NMR (300 MHz, CDCl₃): δ = 11.62 (s, 1 H, H_N–H), 8.33 (d, J = 2.1 Hz, 1 H, H₅), 8.15 (s, 1 H, H₂), 7.86 (d, J = 2.1 Hz, 1 H, H₇), 2.70 (d, J = 7.2 Hz, 2 H, H₉), 1.99 (n, J = 6.9 Hz, 1 H, H₁₀), 0.95 (d, J = 6.7 Hz, 6 H, H₁₁).

¹³C NMR (75 MHz, CDCl₃): δ = 162.55 (C₄), 145.76 (Cq), 143.01 (C₂), 141.09 (Cq), 136.50 (t, J = 8.8 Hz, C₇), 130.74 (C₅), 125.42 (t, J = 22.1 Hz, C₈), 123.77 (Cq), 123.00–105.00 (m, C_CF), 44.99 (C₁₀), 30.39 (C₉), 22.25 (C₁₁).

¹⁹F NMR (282 MHz, CDCl₃): δ = –80.78 to –80.97 (m), –105.35 to –105.56 (m), –120.59 to –120.80 (m), –125.70 (td, J = 13.4, 3.7 Hz).

IR (neat): 3178, 3039, 2966, 2933, 1675, 1618, 1233, 1191, 1182, 1127, 1090, 889, 868, 810, 741, 556 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₆H₁₄F₉N₂O: 421.0962; found: 421.0962.

6-Isobutyl-8-perfluoropentylquinazolin-4(3H)-one (2db)

General Method C was used with 6-(2-methylpropyl)quinazolin-4(3H)-one 1d (70 mg, 0.35 mmol, 1.0 equiv), K₂CO₃ (102 mg, 0.70 mmol, 2.0 equiv) and perfluoropentyl iodide (0.20 mL, 1.27 mmol, 3.0 equiv). The residue was purified with silica gel chromatography (PE/EtOAc, 3:2) to afford 2db (62 mg, 38%) as a white solid; mp 152.7 °C.

¹H NMR (300 MHz, CDCl₃): δ = 11.68 (s, 1 H, H_N–H), 8.33 (d, J = 2.1 Hz, 1 H, H₅), 8.15 (s, 1 H, H₂), 7.86 (d, J = 2.1 Hz, 1 H, H₇), 2.70 (d, J = 7.2 Hz, 2 H, H₉), 1.98 (n, J = 6.8 Hz, 1 H, H₁₀), 0.95 (d, J = 6.6 Hz, 6 H, H₁₁).

¹³C NMR (75 MHz, CDCl₃): δ = 162.50 (C₄), 145.75 (Cq), 142.95 (C₂), 141.13 (Cq), 136.53 (t, J = 9.1 Hz, C₇), 130.75 (C₅), 125.51 (t, J = 22.2 Hz, C₈), 123.77 (Cq), 123.00–105.00 (m, C_CF), 45.00 (C₁₀), 30.39 (C₉), 22.25 (C₁₁).

¹⁹F NMR (282 MHz, CDCl₃): δ = –80.80 (tt, J = 9.9, 2.8 Hz), –105.19 to –105.38 (m), –119.89 to –120.10 (m), –122.22 to –122.44 (m), –125.94 to –126.14 (m).

IR (neat): 3039, 2932, 1677, 1620, 1229, 1204, 1140, 1179, 1140, 808, 732, 556 cm^–1.

HRMS (ESI–): m/z [M – H⁺] calcd for C₁₇H₁₂F₁₁N₂O: 469.0774; found: 469.0773.

2-Cyano-5-perfluorohexylthiazolo[5,4-f]quinazolinone (6a) and 2-Cyano-4-perfluorohexylthiazolo[5,4-f]quinazolinone (6a′)

General Method C was used with 2-cyanothiazolo[5,4-f]quinazolinone 5 (96 mg) and perfluorohexyl iodide (0.27 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 4:1) to afford 6a (146 mg, 64%) as a white solid; mp 233.9 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.33 (s, 1 H, H_N–H), 8.93 (s, 1 H, H₄), 8.58 (s, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.84 (C₉), 150.27 (Cq), 148.39 (Cq), 147.46 (C₇), 142.71 (Cq), 137.05 (Cq), 131.53 (t, J = 9.6 Hz, C₄), 126.23 (t, J = 22.5 Hz, Cq), 123.00–105.00 (m, C_CF), 119.61 (Cq), 113.71 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.67 (tt, J = 10.2, 2.5 Hz), –104.85 (t, J = 17.1, 13.8, 3.4 Hz), –119.37 to –119.64 (m), –121.98 to –122.23 (m), –123.10 to –123.36 (m), –126.63 to –126.89 (m).

IR (neat): 3164, 2913, 2236, 1667, 1615, 1591, 1243, 1211, 1189, 1136, 712, 683, 562, 498 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₈H₇F₁₃N₅OS: 588.0164; found: 588.0178.

Compound 6a′ (42 mg, 18%) was obtained as a white solid; mp 233.3 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.20 (s, 1 H, H_N–H), 8.60 (s, 1 H, H₇), 8.32 (s, 1 H, H₅).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.82 (C₉), 149.87 (Cq), 148.56 (C₇), 147.74 (Cq), 142.14 (Cq), 135.23 (Cq), 129.90 (t, J = 7.7 Hz, C₅), 129.42 (d, J = 24.1 Hz, Cq), 123.00–105.00 (m, C_CF), 120.95 (Cq), 113.81 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.65 (tt, J = 10.0, 2.6 Hz), –107.73 to –108.18 (m), –120.36 to –120.81 (m), –121.81 to –122.13 (m), –123.06 to –123.37 (m), –126.46 to –126.93 (m).

IR (neat): 3152, 3017, 2846, 2242, 1669.8, 1612, 1355, 1243, 1211, 1193, 1137, 1073, 704, 601, 539 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₈H₇F₁₃N₅OS: 588.0164; found: 588.0148.

2-Cyano-5-perfluoropropylthiazolo[5,4-f]quinazolinone (6b) and 2-Cyano-4-perfluoropropyl-thiazolo[5,4-f]quinazolinone (6b′)

General Method C was used with 2-cyanothiazolo[5,4-f]quinazolinone 5 (96 mg) and perfluoropropyl iodide (0.18 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 8:2) to afford 6b (95 mg, 57%) as a white solid; mp 203.5 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.23 (s, 1 H, H_N–H), 8.93 (s, 1 H, H₄), 8.57 (s, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.78 (C₉), 150.23 (Cq), 148.29 (Cq), 147.41 (C₇), 142.67 (Cq), 136.95 (Cq), 131.34 (t, J = 9.6 Hz, C₄), 126.21 (t, J = 22.7 Hz, Cq), 123.00–105.00 (m, C_CF), 122.90–119.86 (m, Cq), 119.52 (Cq), 118.09–115.77 (m, Cq), 113.67 (Cq), 112.03–108.99 (m, Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –80.99 (t, J = 10.1 Hz), –105.56 to –105.74 (m), –123.99 to –124.13 (m).

IR (neat): 3042, 2253, 1665, 1618, 1592, 1352, 1225, 1191, 1114, 950, 845 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₅H₇F₇N₅OS: 438.0260; found: 438.0278.

Compound 6b′ (39 mg, 23%) was obtained as a white solid; mp 247.7 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.29 (s, 1 H, H_N–H), 8.59 (s, 1 H, H₇), 8.30 (s, 1 H, H₅).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.78 (C₉), 149.88 (Cq), 148.50 (C₇), 147.68 (Cq), 142.12 (Cq), 135.21 (Cq), 129.77 (t, J = 8.2 Hz, C₃), 129.08 (Cq), 123.00–105.00 (m, C_CF), 120.95 (Cq), 113.78 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.78 (tt, J = 10.0, 2.8 Hz), –108.16 to –108.33 (m), –121.49 to –121.65 (m), –126.20 to –126.37 (m).

IR (neat): 2998, 2233, 1668, 1611, 1469, 1350, 1272, 1228, 1184, 1117, 931, 903, 805, 755, 738, 725, 541, 448 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₅H₇F₇N₅OS: 438.0260; found: 438.0259.

2-Cyano-5-perfluorobutylthiazolo[5,4-f]quinazolinone (6c) and 2-Cyano-4-perfluorobutylthiazolo[5,4-f]quinazolinone (6c′)

General Method C was used with 2-cyanothiazolo[5,4-f]quinazolinone 5 (96 mg) and perfluorobutyl iodide (0.22 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 4:1) to afford 6c (91 mg, 49 %) as a white solid; mp 236.6 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.27 (s, 1 H, H_N–H), 8.92 (s, 1 H, H₄), 8.58 (s, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.80 (C₉), 150.25 (Cq), 148.36 (Cq), 147.42 (C₇), 142.70 (Cq), 137.03 (Cq), 131.51 (t, J = 9.7 Hz, C₄), 126.29 (t, J = 23.0 Hz, Cq), 123.00–105.00 (m, C_CF), 119.58 (Cq), 113.70 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.65 (tt, J = 10.1, 2.6 Hz), –107.93 to –108.13 (m), –120.74 to –120.95 (m), –122.71 to –122.95 (m), –126.62 to –126.84 (m).

IR (neat): 2921, 2235, 1667, 1592, 1351, 1217, 1135, 904, 823, 743, 722, 536, 440 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₆H₇F₉N₅OS: 488.0228; found: 488.0237.

Compound 6c′ (38 mg, 20%) was obtained as a white solid; mp 225.7 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.26 (s, 1 H, H_N–H), 8.60 (s, 1 H, H₇), 8.31 (s, 1 H, H₅).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.79 (C₉), 149.88 (Cq), 148.51 (C₇), 147.74 (Cq), 142.15 (Cq), 135.23 (Cq), 129.95 (t, J = 8.3 Hz, C₅), 129.11 (t, J = 11.0 Hz, C₄), 123.00–105.00 (m, C_CF), 120.98 (Cq), 113.81 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.78 (tt, J = 10.0, 2.8 Hz), –108.16 to –108.32 (m), –121.52 to –121.62 (m), –126.20 to –126.37 (m).

IR (neat): 3011, 2895, 2240, 1668, 1610, 1351, 1236, 1197, 1130, 868, 792, 753, 719, 536 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₆H₇F₉N₅OS: 488.0228; found: 488.0232.

2-Cyano-5-perfluoropentylthiazolo[5,4-f]quinazolinone (6d) and 2-Cyano-4-perfluoropentyl-thiazolo[5,4-f]quinazolinone (6d′)

General Method C was used with 2-cyanothiazolo[5,4-f]quinazolinone 5 (96 mg) and perfluoropentyl iodide (96 mL). The residue was purified with silica gel chromatography (DCM/EtOAc, 4:1) to afford 6d (112 mg, 54%) as a white solid; mp 233.3 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.29 (s, 1 H, H_N–H), 8.91 (s, 1 H, H₄), 8.58 (s, 1 H, H₇).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.81 (C₉), 150.26 (Cq), 148.37 (Cq), 147.44 (C₇), 142.70 (Cq), 137.03 (Cq), 131.51 (t, J = 9.7 Hz, C₄), 126.36 (t, J = 22.7 Hz, Cq), 123.00–105.00 (m, C_CF), 119.58 (Cq), 113.69 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.65 (tt, J = 10.1, 2.6 Hz), –107.93 to –108.13 (m), –120.74 to –120.95 (m), –122.71 to –122.95 (m), –126.62 to –126.84 (m).

IR (neat): 3162, 3047, 2926, 2233, 1664, 1616, 1591, 1361, 1242, 1228, 1189, 1133, 796, 739, 653, 531 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₇H₇F₁₁N₅OS: 538.0196; found: 538.0193.

Compound 6d′ (38 mg, 18%) was obtained as a white solid; mp 207.7 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 12.27 (s, 1 H, H_N–H), 8.60 (s, 1 H, H₇), 8.32 (s, 1 H, H₅).

¹³C NMR (75 MHz, acetone-d ₆): δ = 159.79 (C₉), 149.92 (Cq), 148.51 (C₇), 147.75 (Cq), 142.16 (Cq), 135.25 (Cq), 129.92 (t, J = 8.2 Hz, C₅), 129.25 (Cq), 123.00–105.00 (m, C_CF), 120.99 (Cq), 113.83 (Cq).

¹⁹F NMR (282 MHz, acetone-d ₆): δ = –81.57 to –81.73 (m), –107.93 to –108.14 (m), –120.74 to –120.94 (m), –122.71 to –122.94 (m), –126.62 to –126.84 (m).

IR (neat): 3150, 2853, 2233, 1668, 1612, 1600, 1354, 1239, 1189, 1133, 1118, 912, 778, 707, 532 cm^–1.

HRMS (ESI+): m/z [M + CH₃CN + H⁺] calcd for C₁₇H₇F₁₁N₅OS: 538.0196; found: 538.0194.

Synthesis of Compounds 7–10

4-N-Benzylamino-perfluorohexylquinazoline (7)

In a sealed microwave vial, 8-perfluorohexylquinazolin-4(3H)-one 2a (200 mg, 0.431 mmol, 1 equiv), was dissolved in POCl₃ (1 mL) and the reaction was heated at 106 °C for 16 h. The reaction was then quenched on ice/NaHCO₃ and the mixture was extracted with DCM and dried over MgSO₄. Without further purification, benzylamine (1 mL) was added dropwise and the mixture was heated at 100 °C for 10 min. At room temperature, the mixture was quenched with HCl until acidic pH. The crude product was extracted with DCM, washed with brine, dried over MgSO₄, and then purified by silica gel chromatography (DCM/EtOAc, 3:2) to afford 7 (68 mg, 57%) as a white solid; mp 125.7 °C.

¹H NMR (300 MHz, acetone-d ₆): δ = 8.60 (s, 1 H, H₂), 8.57 (dd, J = 8.4, 1.3 Hz, 1 H, H₅), 8.26 (s, 1 H, H_N–H), 8.15 (dd, J = 7.6, 1.3 Hz, 1 H, H₇), 7.70 (t, J = 7.9 Hz, 1 H, H₆), 7.49–7.39 (m, 2 H, H₁₂), 7.38–7.19 (m, 3 H, H_13,14), 4.92 (d, J = 5.8 Hz, 2 H, H₁₀).

¹³C NMR (75 MHz, CDCl₃): δ = 160.74 (C₄), 156.60 (C₂), 149.00 (Cq), 139.95 (Cq), 134.10 (t, J = 9.4 Hz, C₇), 129.26 (C₁₃), 128.59 (C₁₂), 128.20 (Cq), 127.93 (C₁₄), 125.83 (t, J = 21.7 Hz, C₈), 125.61 (C₆), 123.00–105.00 (m, C_CF), 116.86 (Cq), 45.21 (C₁₀).

¹⁹F NMR (282 MHz, CDCl₃): δ = –76.49 (tt, J = 10.2, 2.6 Hz), –99.60 to –99.86 (m), –114.23 to –114.51 (m), –116.90 to –117.00 (m), –116.79 to –117.12 (m), –117.84 to –118.16 (m), –121.41 to –121.70 (m).

IR (neat): 3341, 1594, 1544, 1289, 1234, 1197, 1146, 780, 729, 693 cm^–1.

HRMS (ESI+): m/z [M – H⁺] calcd for C₂₁H₁₁F₁₃N₃: 552.0735; found: 552.0741.

N ³-Pyridinyl-8-perfluorohexylquinazolin-4(3H)-one (8)

In a sealed microwave vial, a mixture of compound 2a (200 mg, 0.431 mmol, 1 equiv), 2-bromopyridine (136 mg, 0.862 mmol, 2 equiv), K₂CO_3­ (60 mg, 0.431 mmol, 1 equiv), and CuI (8 mg, 0.043 mmol, 0.1 equiv) in DMF (3 mL) was heated to 150 °C for 16 h. The crude product was extracted with DCM, dried over MgSO₄ and then purified by silica gel chromatography (PE/EtOAc, 4:1) to afford 8 (135 mg, 58%) as a white solid; mp 127.7 °C.

¹H NMR (300 MHz, CDCl₃): δ = 8.72 (s, 1 H, H₂), 8.68–8.57 (m, 2 H, H_5,13), 8.07 (dd, J = 7.7, 1.6 Hz, 1 H, H₇), 7.92 (dd, J = 2.0, 1.4 Hz, 1 H, H₁₀), 7.90 (d, J = 1.4 Hz, 1 H, H₁₁), 7.70–7.59 (t,J = 7.7 Hz, 1 H, H₆), 7.44–7.36 (m, 1 H, H₁₂).

¹³C NMR (75 MHz, CDCl₃): δ = 159.86 (C₄), 149.51 (C₁₃), 149.38 (Cq), 146.44 (d, J = 1.8 Hz, Cq), 145.32 (C₂), 138.35 (C₁₁), 134.95 (t, J = 8.9 Hz, C₇), 132.01 (C₅), 126.90 (C₆), 125.89 (t, J = 22.3 Hz, C₈), 123.99 (C₁₂), 123.83 (Cq), 121.45 (C₁₀), 121.00–105.00 (m, C_CF).

IR (neat): 1698, 1621, 1574, 1436, 1238, 1209, 1146, 783, 728, 692, 651, 516 cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₁₉H₉F₁₃N₃O: 542.0538; found: 542.0533.

General Method F

Quinazolinone 2a–4a (1.0 equiv), K₂CO₃ (5 equiv), NaI (0.1 equiv) and benzyl bromide (1.3 equiv) were dissolved in acetone. The reaction mixture was heated at 50 °C for 20 h. The crude mixture was extracted with DCM, dried over MgSO₄, and concentrated under vacuum. The crude product was purified by flash chromatography on silica gel to afford 2n, 9, or 10.

N ³-Benzyl-8-perfluorohexylquinazolin-4(3H)-one (2n)

General method F was used with 2a (100 mg, 0.22 mmol, 1.0 equiv), K₂CO₃ (149 mg, 1.08 mmol, 5 equiv), NaI (3 mg, 0.02 mmol, 0.1 equiv) and benzyl bromide (45 mg, 0.29 mmol, 1.3 equiv) were dissolved in acetone (5 mL). The residue was purified with silica gel chromatography (PE/EtOAc, 4:1) to afford 2n (104 mg, 85%) as a white solid; mp 92.6 °C.

¹H NMR (300 MHz, CDCl₃): δ = 8.64–8.52 (m, 1 H, H₅), 8.19 (s, 1 H, H₂), 8.02 (dd, J = 7.7, 1.6 Hz, 1 H, H₇), 7.65–7.57 (m, 1 H, H₆), 7.42–7.30 (m, 5 H, H_11,12,13), 5.19 (s, 2 H, CH₂, H₉).

¹³C NMR (75 MHz, CDCl₃): δ = 160.48 (C₄), 146.71 (Cq), 146.68 (C₂), 135.27 (C_8a), 134.63 (t, J = 7.7 Hz, C₇), 131.75 (C₅), 129.29 (C_11or12), 128.73 (C₁₃), 128.49 (C_11or12), 126.61 (C₆), 125.62 (t, J = 22.2 Hz, C₈), 123.74 (C_4a), 120.21 (t, J = 33.0 Hz, C_CF), 119.28 (t, J = 33.1 Hz, C_CF), 116.76 (t, J = 34.9 Hz, C_CF), 115.50 (t, J = 33.8 Hz, C_CF), 112.13–110.42 (m, C_CF), 108.37 (t, J = 34.0 Hz, C_CF), 49.95 (CH₂, C₉).

¹⁹F NMR (282 MHz, CDCl₃): δ = –80.80 (tt, J = 10.2, 2.7 Hz), –105.20 (tt, J = 13.4, 3.1 Hz), –119.55 to –119.80 (m), –121.46 to –121.72 (m), –122.53 to –122.80 (m), –126.01 to –126.24 (m).

IR (neat): 3071, 2950, 1667, 1611, 1239, 1192, 1143, 1136, 769, 717, 666, 630cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₂₁H₁₂N₂OF₁₃: 555.0742; found: 555.0730.

N ³-Benzyl-5,8-bisperfluorohexylquinazolin-4(3H)-one (9)

General method F was used with compound 3a (65 mg, 0.08 mmol, 1.0 equiv), K₂CO₃ (57 mg, 0.42 mmol, 5 equiv), NaI (2 mg, 0.01 mmol, 0.15 equiv) and benzyl bromide (39 mg, 0.19 mmol, 2.3 equiv) in acetone (5 mL). The residue was purified with silica gel chromatography (PE/EtOAc, 4:1) to afford 9 (58 mg, 81%) as a yellowish oil.

¹H NMR (300 MHz, CDCl₃): δ = 8.17 (s, 1 H, H₂), 8.12 (d, J = 8.3 Hz, 1 H, H₇), 7.94 (d, J = 8.3 Hz, 1 H, H₆), 7.37 (s, 5 H, H_Ph), 5.21 (s, 2 H, CH₂, H₉).

¹³C NMR (75 MHz, CDCl₃): δ = 157.32 (C₄), 149.17 (Cq), 147.18 (C₂), 134.88 (Cq), 133.81–133.31 (m, C₇ and Cq),130.57 (t, J = 22.6 Hz, Cq), 129.40 (C_11or12), 128.91 (C₁₃), 128.74 (C_11or12),127.51 (t, J = 12.3 Hz, C₆), 122.71 (Cq), 120.09–118.46 (m, C_CF), 117.72–114.46 (m, C_CF), 113.02–110.40 (m, C_CF), 109.20–106.81 (m, C_CF), 105.65–103.51 (m, C_CF), 49.94 (CH₂, C₉).

¹⁹F NMR (282 MHz, CDCl₃): δ = –80.53 to –80.95 (m), –97.38 (tt, J = 15.3, 3.3 Hz), –105.22 (tt, J = 17.8, 3.9 Hz), –115.00 to –115.49 (m), –118.59 to –119.07 (m), –121.46 to –121.88 (m), –122.15 to –122.83 (m), –125.77 to –126.33 (m).

IR (neat): 2920, 2846, 1700, 1625, 1591, 1231, 1195, 1142, 1121, 730, 713, 695, 682, 568cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₂₇H₁₁N₂OF₂₆: 873.0456; found: 873.0455.

N ³-Benzyl-6,8-bisperfluorohexylquinazolin-4(3H)-one (10)

General method F was used with compound 4a (100 mg, 0.128 mmol, 1.0 equiv), K₂CO₃ (88 mg, 0.64 mmol, 5 equiv), NaI (2.0 mg, 0.13 mmol, 0.1 equiv) and benzyl bromide (45 mg, 0.29 mmol, 2.3 equiv) in acetone (5 mL). The residue was purified with silica gel chromatography (PE/EtOAc, 9:1) to afford 10 (95 mg, 85%) as a white solid; mp 99.3 °C.

¹H NMR (300 MHz, CDCl₃): δ = 8.83 (d, J = 2.1 Hz, 1 H, H₅), 8.29 (s, 1 H, H₂), 8.15 (d, J = 2.2 Hz, 1 H, H₇), 7.44–7.32 (m, 5 H, H_11,12,13), 5.21 (s, 2 H, H₉).

¹³C NMR (75 MHz, CDCl₃): δ = 159.74 (C₄), 149.03 (Cq), 148.72 (C₂), 134.69 (Cq), 132.58–132.04 (m, C₇), 131.49–131.15 (m, C₅), 129.45 (C_11or12), 129.05 (C₁₃), 128.66 (C_11or12), 127.41 (t, J = 25.7 Hz, Cq), 126.98 (t, J = 22.8 Hz, Cq), 124.07 (Cq), 119.85–118.29 (m, C_CF), 116.40–114.19 (m, C_CF), 112.48–110.34 (m, C_CF), 108.63–106.07 (m, C_CF), 50.31 (C₉).

¹⁹F NMR (282 MHz, CDCl₃): δ = –80.93 (tt, J = 9.7, 3.0 Hz), –105.69 (tt, J = 16.4, 3.5 Hz), –110.80 (tt, J = 15.1, 3.6 Hz), –119.66 to –119.94 (m), –121.27 to –121.46 (m), –121.46 to –121.73 (m), –122.66 to –122.95 (m), –126.10 to –126.36 (m).

IR (neat): 1699, 1610, 1243, 1198, 1141, 694, 713, 657cm^–1.

HRMS (ESI+): m/z [M + H⁺] calcd for C₂₇H₁₁N₂OF₂₆: 873.0456; found: 873.0460.

Conflict of Interest

The authors declare no conflict of interest.

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Corresponding Author

Publication History

Received: 31 January 2023

Accepted after revision: 14 March 2023

Accepted Manuscript online:
14 March 2023

Article published online:
11 April 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

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• Supplementary Material