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DOI: 10.1055/s-0029-1218607
Synthesis of New Aminonicotinate Derivatives from Acetylated Baylis-Hillman Adducts and Enamino Esters via a Consecutive [3+3]-Annulation Protocol
Publication History
Publication Date:
16 December 2009 (online)
Abstract
A one-pot, consecutive [3+3]-annulation protocol is described for the synthesis of new aminonicotinate derivatives from acetylated Baylis-Hillman adducts and enamino esters.
Key words
Michael addition - cyclization - isomerization - hydrolysis - heterocycles
Multisubstituted pyridines represent molecular frameworks that serve as a platform for developing pharmaceutical agents for various applications. Among these, aminopyridine and nicotinate analogues constitute an important class of compounds in organic synthesis and drug discovery. [¹] A large number of aminopyridine derivatives have been reported to exhibit antitumor, [²a] [b] vasodilator [²c] and anti-inflammatory [²d] activities. A few aminopyridine derivatives have recently been screened as NCX inhibitors. [²e] Moreover, aminopyridine derivatives are the key intermediates in the synthesis of the corresponding 1,8-naphthyridines, [³] 7-azaindoles, [4] oxazolopyridines [5] and imidazopyridines. [6] In addition to pharmaceutical applications, aminopyridine derivatives have been used as ligands for transition-metal complexes, [7] as fluorescent dyes [8] and also for agricultural products. [9]
A survey of the literature shows that derivatization of a 2-unsubstituted pyridine moiety in a complex molecule to the corresponding 2-aminopyridine is often desired but only achieved in a long sequence and with low efficiency. [¹0] There are several methods available in the literature for the synthesis of 2-aminopyridine derivatives. [¹¹] One of the most traditional approaches is amination of 2-halopyridines and analogues with ammonia or an equivalent under high temperature (150-250 ˚C) and pressure. [²e] [¹²] The second approach is the Chichibabin reaction [¹b] [¹³] where 2-aminopyridines can be directly obtained from sodium amide and pyridines. There are some limitations, however, with the procedures for the synthesis of 2-aminopyridines suffering from the use of high reaction temperatures and prolonged reaction times, poor regioselectivity and low product yields. Due to the immense biological importance, the development of simple and convenient approaches to 2-aminopyridines from easily available starting materials is very much required.
In recent years the Baylis-Hillman reaction has attracted the attention of many organic chemists, because it is a simple, straightforward method for the generation of attractive densely functionalized molecules. [¹4] Recently, we have reported the synthesis of Baylis-Hillman adducts and have converted them into quinolines, 1,8-naphthyridines and 2-pyridones. [¹5] So far, no report exists in the literature on the synthesis of aminonicotinate derivatives from Baylis-Hillman adducts. In continuation of our research on the synthesis of heterocyclic compounds and applications of Baylis-Hillman chemistry, [¹5] [¹6] we now describe a facile, one-pot synthesis of aminonicotinate derivatives via treatment of acetylated Baylis-Hillman nitriles with enamino esters by way of a [3+3]-annulation process.
The starting materials, acetylated Baylis-Hillman nitriles 1a-g and enamines 2a,b (Table [¹] ), were synthesized according to literature procedures. [¹7] Enamino ester 2a was treated with sodium hydride in anhydrous tetrahydrofuran at room temperature, and acetylated Baylis-Hillman nitrile 1a was added. The reaction was completed in six hours and furnished the desired product 3a in good yield (Table [¹] ). We have examined this reaction by using different bases (K2CO3, Et3N, t-BuOK, NaH) and varying the equivalents, from one to three, separately. Potassium carbonate and triethylamine failed to promote the reaction, whereas in the case of potassium tert-butoxide the yield was lower than when sodium hydride was used. So, finally, we concluded that three equivalents of sodium hydride are suitable to promote the reaction. Encouraged by this result, we have successfully transformed several representative acetylated Baylis-Hillman nitriles 1b-g via treatment with enamino ester 2a or 2b into the desired substituted aminonicotinate derivatives 3b-j in good yields (Table [¹] ). All of the aminonicotinates synthesized were characterized by spectroscopic techniques and 3a was additionally characterized by X-ray crystallographic studies (Figure [¹] ).
Figure 1 ORTEP diagram of compound 3a
A plausible mechanism for the formation of aminonicotinate derivative 3a is shown in Scheme [¹] . The resonance-stabilized anion generated by the action of sodium hydride on the amino group of enamine 2a attacks through its α-carbon (which is nucleophilic in nature) at the β-carbon of the external double bond of the acetylated Baylis-Hillman nitrile 1a via an SN2′ mechanism, by which C-C bond formation takes place and subsequent migration of the double bond with elimination of the acetate group occurs simultaneously to give intermediate I which was not isolated during the reaction. Thus formed, intermediate I undergoes a proton shift as well as intramolecular cyclization to give the six-membered cyclic intermediate II. In this annulation protocol, the two-carbon and one-nitrogen source from the enamino ester with the three-carbon source from the acetylated Baylis-Hillman nitrile gives the [3+3]-cyclized product II. Subsequently, double-bond migration takes place and gives aminonicotinate 3a in good yield after the usual workup. The beauty of this reaction is that three chemical transformations [i.e., addition, cyclization, isomerization (proton shifts)] take place in one pot leading to the aminonicotinate derivative.
Scheme 1
In summary, we have developed a straightforward, convenient and practical synthesis of aminonicotinate derivatives from acetylated Baylis-Hillman nitriles and enamino esters, via a [3+3]-annulation protocol, in moderate to good yields. We believe this reaction has enough scope for further investigations.
Melting points were determined on a Mel-Temp apparatus and are uncorrected. IR spectra were recorded using a Thermo Nicolet Nexus 670 FTIR spectrometer. ¹H and ¹³C NMR spectra were recorded on either a Bruker Avance 300-MHz or a Varian Inova 400-MHz FT spectrometer, using TMS as an internal standard (chemical shift values in δ, J in Hz). HRMS (ESI) data were recorded on a QSTAR XL high-resolution mass spectrometer. GC-MS data were recorded on an Agilent 6890 series GC-MS system (column: Varian CP-Sil 8 CB, 5% phenyl, 95% PDMS, 30.0 m × 250 µm × 0.30 µm nominal).
Aminonicotinate Derivatives 3a-j; General Procedure
To a well-stirred solution of NaH (60% in paraffin oil; 240 mg, 6 mmol) in anhyd THF (15 mL) was added the enamino ester 2a or 2b (2 mmol) dissolved in anhyd THF (5 mL) at r.t. under N2 atmosphere, and the mixture was stirred for 15 min at the same temperature. Then, an acetylated Baylis-Hillman nitrile 1a-g (2.2 mmol) dissolved in anhyd THF (5 mL) was added slowly and the mixture was stirred at r.t. until the reaction was completed. After completion, the solvent was removed under reduced pressure and the residue was diluted with ice-cold H2O (15 mL) and extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with H2O (10 mL), dried (Na2SO4), concentrated under reduced pressure and purified by silica gel column chromatography (EtOAc-hexane, 1:9 followed by 1:4) to afford pure compound 3a-j.
Ethyl 6-Amino-5-benzyl-2-methylnicotinate (3a)
Yield: 68%; white solid; mp 137-139 ˚C.
IR (KBr): 3436, 3326, 3130, 1695, 1655, 1597, 1470, 1243 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.30-7.13 (m, 5 H), 4.71 (s, 2 H), 4.28 (q, J = 7.6 Hz, 2 H), 3.83 (s, 2 H), 2.65 (s, 3 H), 1.37 (t, J = 7.6 Hz, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 166.6, 159.0, 158.2, 141.1, 137.5, 128.9, 128.2, 126.9, 115.5, 115.3, 60.4, 37.1, 24.2, 14.3.
GC-MS (EI, 70 eV): m/z (%) = 270 (100) [M+], 254, 241, 225, 197, 180, 152, 127, 105, 91, 77, 43.
HRMS (ESI): m/z calcd for C16H19N2O2 [M + H]+: 271.1446; found: 271.1456.
Ethyl 6-Amino-5-(4-fluorobenzyl)-2-methylnicotinate (3b)
Yield: 65%; white solid; mp 131-133 ˚C.
IR (KBr): 3487, 3313, 3112, 2980, 1708, 1647, 1598, 1507, 1260 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.85 (s, 1 H), 7.12 (q, J = 8.3 Hz, 2 H), 6.97 (t, J = 8.3 Hz, 2 H), 4.59 (br s, 2 H), 4.28 (q, J = 6.8 Hz, 2 H), 3.80 (s, 2 H), 2.65 (s, 3 H), 1.37 (t, J = 6.8 Hz, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 166.6, 163.4, 160.1, 159.3, 158.1, 141.0, 133.2, 133.1, 129.8, 129.7, 115.9, 115.6, 115.2, 115.2, 60.4, 36.3, 24.4, 14.3.
GC-MS (EI, 70 eV): m/z (%) = 288 (100) [M+], 273, 259, 243, 215, 198, 171, 146, 133, 120, 109, 100, 51.
HRMS (ESI): m/z calcd for C16H18N2O2F [M + H]+: 289.1352; found: 289.1342.
Ethyl 6-Amino-2-methyl-5-(4-methylbenzyl)nicotinate (3c)
Yield: 61%; white solid; mp 122-124 ˚C.
IR (KBr): 3483, 3299, 3105, 2985, 1705, 1642, 1559, 1261 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.89 (s, 1 H), 7.10 (d, J = 8.1 Hz, 2 H), 7.04 (d, J = 8.1 Hz, 2 H), 4.61 (br s, 2 H), 4.29 (q, J = 7.2 Hz, 2 H), 3.79 (s, 2 H), 2.66 (s, 3 H), 2.32 (s, 3 H), 1.37 (t, J = 7.2 Hz, 3 H).
¹³C NMR (75 MHz, DMSO-d 6): δ = 165.9, 158.9, 157.6, 138.9, 135.9, 135.0, 128.9, 128.5, 116.1, 112.4, 59.5, 34.6, 24.1, 20.5, 14.1.
GC-MS (EI, 70 eV): m/z (%) = 284 (100) [M+], 269, 255, 239, 211, 194, 178, 167, 152, 141, 119, 105, 91, 77, 51.
HRMS (ESI): m/z calcd for C17H21N2O2 [M + H]+: 285.1603; found: 285.1604.
Ethyl 6-Amino-5-(4-chlorobenzyl)-2-methylnicotinate (3d)
Yield: 70%; pale yellow solid; mp 175-177 ˚C.
IR (KBr): 3477, 3308, 3141, 2982, 1714, 1643, 1561, 1258 cm-¹.
¹H NMR (300 MHz, CDCl3 + DMSO-d 6): δ = 7.69 (s, 1 H), 7.24 (d, J = 8.6 Hz, 2 H), 7.15 (d, J = 8.6 Hz, 2 H), 5.65 (s, 2 H), 4.21 (q, J = 7.0 Hz, 2 H), 3.77 (s, 2 H), 2.58 (s, 3 H), 1.33 (t, J = 7.0 Hz, 3 H).
¹³C NMR (75 MHz, DMSO-d 6): δ = 165.8, 158.9, 158.0, 139.2, 138.2, 130.7, 130.4, 128.2, 115.4, 112.3, 59.6, 34.2, 24.2, 14.1.
GC-MS (EI, 70 eV): m/z (%) = 304 (100) [M+], 289, 275, 259, 243, 231, 214, 196, 181, 167, 152, 125, 112, 99, 77, 52.
HRMS (ESI): m/z calcd for C16H18N2O2Cl [M + H]+: 305.1056; found: 305.1046.
Ethyl 6-Amino-5-(4-bromobenzyl)-2-methylnicotinate (3e)
Yield: 69%; pale yellow solid; mp 187-189 ˚C.
IR (KBr): 3475, 3307, 3141, 2982, 2931, 1712, 1642, 1562, 1256 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 7.85 (s, 1 H), 7.42 (d, J = 8.3 Hz, 2 H), 7.04 (d, J = 8.3 Hz, 2 H), 4.54 (br s, 2 H), 4.28 (q, J = 6.8 Hz, 2 H), 3.78 (s, 2 H), 2.65 (s, 3 H), 1.37 (t, J = 6.8 Hz, 3 H).
¹³C NMR (75 MHz, DMSO-d 6): δ = 165.9, 159.0, 158.0, 139.3, 138.6, 131.1, 130.8, 119.1, 115.3, 112.3, 60.0, 34.3, 24.2, 14.2.
GC-MS (EI, 70 eV): m/z (%) = 348 (100) [M+], 319, 303, 275, 240, 224, 206, 195, 181, 169, 153, 127, 102, 90, 77, 52.
HRMS (ESI): m/z calcd for C16H18N2O2Br [M + H]+: 349.0551; found: 349.0540.
Ethyl 6-Amino-5-(2-chlorobenzyl)-2-methylnicotinate (3f)
Yield: 68%; white solid; mp 164-166 ˚C.
IR (KBr): 3479, 3312, 3141, 2981, 2929, 1711, 1647, 1563, 1254 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.83 (s, 1 H), 7.39 (q, J = 5.3 Hz, 1 H), 7.20-7.13 (m, 2 H), 6.98 (q, J = 5.3 Hz, 1 H), 4.78 (br s, 2 H), 4.26 (q, J = 6.8 Hz, 2 H), 3.90 (s, 2 H), 2.65 (s, 3 H), 1.35 (t, J = 6.8 Hz, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 166.6, 159.3, 158.1, 141.2, 135.2, 134.1, 129.8, 129.6, 128.3, 127.2, 115.6, 114.1, 60.4, 34.1, 24.4, 14.3.
GC-MS (EI, 70 eV): m/z (%) = 304 (49) [M+], 269 (100), 259, 241, 225, 195, 181, 167, 152, 125, 112, 99, 77, 51.
HRMS (ESI): m/z calcd for C16H18N2O2Cl [M + H]+: 305.1056; found: 305.1049.
Ethyl 6-Amino-5-(3-bromobenzyl)-2-methylnicotinate (3g)
Yield: 65%; white solid; mp 124-126 ˚C.
IR (KBr): 3485, 3303, 3142, 2977, 1700, 1643, 1558, 1258 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.87 (s, 1 H), 7.37 (d, J = 7.9 Hz, 1 H), 7.30 (s, 1 H), 7.16 (t, J = 7.7 Hz, 1 H), 7.07 (d, J = 7.5 Hz, 1 H), 4.65 (br s, 2 H), 4.30 (q, J = 7.2 Hz, 2 H), 3.81 (s, 2 H), 2.65 (s, 3 H), 1.37 (t, J = 7.2 Hz, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 166.5, 159.5, 158.0, 141.2, 140.0, 131.2, 130.4, 130.1, 126.8, 123.0, 115.6, 114.4, 60.4, 36.6, 24.4, 14.3.
GC-MS (EI, 70 eV): m/z (%) = 348 (100) [M+], 319, 303, 275, 240, 226, 195, 181, 169, 153, 127, 115, 97, 77, 52.
HRMS (ESI): m/z calcd for C16H18N2O2Br [M + H]+: 349.0551; found: 349.0569.
Methyl 6-Amino-5-benzyl-2-methylnicotinate (3h)
Yield: 56%; white solid; mp 144-147 ˚C.
IR (KBr): 3482, 3307, 3133, 2946, 1709, 1646, 1559, 1262 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.30-7.12 (m, 5 H), 4.65 (br s, 2 H), 3.82 (s, 5 H), 2.65 (s, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 167.0, 159.4, 158.3, 141.0, 137.5, 128.9, 128.3, 126.9, 115.5, 115.1, 51.5, 37.2, 24.4.
GC-MS (EI, 70 eV): m/z (%) = 256 (100) [M+], 241, 225, 195, 180, 153, 127, 115, 103, 91, 77, 51.
HRMS (ESI): m/z calcd for C15H17N2O2 [M + H]+: 257.1290; found: 257.1296.
Methyl 6-Amino-5-(4-fluorobenzyl)-2-methylnicotinate (3i)
Yield: 55%; pale yellow solid; mp 151-154 ˚C.
IR (KBr): 3486, 3305, 3157, 2955, 1713, 1640, 1559, 1243 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.13 (q, J = 8.6 Hz, 2 H), 6.96 (t, J = 8.6 Hz, 2 H), 5.23 (s, 2 H), 3.79 (s, 3 H), 3.77 (s, 2 H), 2.75 (s, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 166.9, 163.4, 160.2, 159.5, 158.1, 140.9, 133.2, 133.1, 129.8, 129.7, 115.9, 115.6, 115.3, 115.2, 51.6, 36.3, 24.4.
GC-MS (EI, 70 eV): m/z (%) = 274 (100) [M+], 259, 243, 213, 171, 147, 133, 109, 83, 52.
HRMS (ESI): m/z calcd for C15H16N2O2F [M + H]+: 275.1195; found: 275.1199.
Methyl 6-Amino-5-(4-chlorobenzyl)-2-methylnicotinate (3j)
Yield: 58%; pale yellow solid; mp 175-177 ˚C.
IR (KBr): 3476, 3310, 3118, 2941, 1720, 1645, 1563, 1257 cm-¹.
¹H NMR (300 MHz, CDCl3): δ = 7.86 (s, 1 H), 7.28 (d, J = 8.3 Hz, 2 H), 7.10 (d, J = 8.3 Hz, 2 H), 4.60 (br s, 2 H), 3.83 (s, 3 H), 3.79 (s, 2 H), 2.66 (s, 3 H).
¹³C NMR (75 MHz, CDCl3): δ = 166.9, 159.6, 158.1, 141.1, 136.0, 132.8, 129.6, 129.0, 115.3, 114.9, 51.6, 36.4, 24.4.
GC-MS (EI, 70 eV): m/z (%) = 290 (100) [M+], 275, 259, 231, 216, 196, 178, 152, 125, 97, 77, 52.
HRMS (ESI): m/z calcd for C15H16N2O2Cl [M + H]+: 291.0900; found: 291.0899.
X-ray Crystallography of Compound 3a [¹8]
A colorless cube crystal of compound 3a was obtained from CHCl3.
C16H18N2O2, M = 270.32, monoclinic, space group P21/n, a = 12.7513(2) Å, b = 7.4527(1) Å, c = 17.7352(3) Å, β = 111.069(4)˚, V = 1572.7(5) ų, ρ = 1.142 g/cm³, F(000) = 576. X-ray diffraction data were collected using a Bruker SMART CCD area detector at 293 K, using graphite monochromated Mo Kα radiation (λ = 0.71073 Å). Integration and scaling of intensity data were accomplished using SAINT. [¹9a] The structure was solved by direct methods and refined by the full-matrix least-squares procedure based on F [¹9b] using the program SHELX-97. [¹9b] Non-hydrogen atoms were refined with anisotropic displacement parameters and hydrogen atoms were included in the models at their calculated positions in a riding model approximation. The molecular geometry and graphics were computed using the programs PARST [¹9c] and ORTEP-3. [¹9d] The ORTEP view of the molecule is shown in Figure [¹] .
Acknowledgment
The authors thank the Director, IICT and the Head of the Division Organic-II for encouragement. M.R., P.S.S. and A.S. thank CSIR, New Delhi for fellowships.
- 1a
Scriven EFV. In Comprehensive Heterocyclic Chemistry Part 2, Vol. 2:Boulton AJ.McKillop A. Pergamon; New York: 1984. p.165-314 - 1b
Leffler MT. Org. React. 1942, 1: 91 - 1c
McGill CK.Rappa A. Adv. Heterocycl. Chem. 1988, 44: 1 - 1d
Landriscina M.Prudovsky I.Carreira CM.Soldi R.Tarantini F.Maciag T. J. Biol. Chem. 2000, 275: 32753 - 1e
Henry GD. Tetrahedron 2004, 60: 6043 - 1f
Scipione L.De Vita D.Musella A.Flammini L.Bertoni S.Barocelli E. Bioorg. Med. Chem. Lett. 2008, 18: 309 - 1g
Lawton GR.Ranaivo HR.Chico LK.Ji H.Xue F.Martásek P.Roman LJ.Watterson M.Silverman RB. Bioorg. Med. Chem. 2009, 17: 2371 - 1h
Lechat P.Tesleff S.Bownan WC. Aminopyridines and Similarly Acting Drugs Pergamon; Oxford: 1982. - 1i
Zhang J.Pettersson HI.Huitema C.Niu C.Yin J.James MNG.Eltis LD.Vederas JC. J. Med. Chem. 2007, 50: 1850 - 2a
Cocco MT.Congiu C.Lilliu V.Onnis V. Bioorg. Med. Chem. 2007, 15: 1859 - 2b
Amr A.-GE.Mohamed AM.Mohamed SF.Abdel-Hafez NA.Hammam AE.- FG. Bioorg. Med. Chem. 2006, 14: 5481 - 2c
Girgis AS.Kalmouch A.Ellithey M. Bioorg. Med. Chem. 2006, 14: 8488 - 2d
Murata T.Shimada M.Sakakibara S.Yoshino T.Masuda T.Shintani T.Sato H.Koriyama Y.Fukushima K.Nunami N.Yamauchi M.Fuchikami K.Komura H.Watanabe A.Ziegelabauer KB.Bacon KB.Lowinger TB. Bioorg. Med. Chem. Lett. 2004, 14: 4019 - 2e
Kuramochi T.Kakefuda A.Yamada H.Tsukamoto I.Taguchi T.Sakamoto S. Bioorg. Med. Chem. 2005, 13: 4022 - 3a
Dormer PG.Eng KK.Farr RN.Humphrey GR.McWilliams JC.Reider PJ.Sager JW.Volante RP. J. Org. Chem. 2003, 68: 467 - 3b
Hamada Y.Takeuchi I. Chem. Pharm. Bull. 1971, 19: 1857 - 3c
Zhichkin P.Beer CMC.Rennells WM.Fairfax DJ. Synlett 2006, 379 - 3d
Hsiao Y.Rivera NR.Yasuda N.Hughes DL.Reider PJ. Org. Lett. 2001, 3: 1101 - 4a
Cottineau B.O’Shea DF. Tetrahedron Lett. 2005, 46: 1935 - 4b
Ujjainwalla F.Walsh TF. Tetrahedron Lett. 2001, 42: 6441 - 5a
Myllymäki MJ.Koskinen AMP. Tetrahedron Lett. 2007, 48: 2295 - 5b
Bemis JE.Vu CB.Xie R.Nunes JN.Ng PY.Disch JS.Milne JC.Carney DP.Lynch AV.Jin L.Smith JJ.Lavu S.Iffland A.Jirousek MR.Perni RB. Bioorg. Med. Chem. Lett. 2009, 19: 2350 - 6a
Andaloussi M.Moreau E.Chavignon O.Teulade JC. Tetrahedron Lett. 2007, 48: 8392 - 6b
Hamama WS.Zoorob HH. Tetrahedron 2002, 58: 6143 - 6c
Adib M.Sheibani E.Zhu L.-G.Mirzaei P. Tetrahedron Lett. 2008, 49: 5108 - 7a
Deeken S.Proch S.Casini E.Braun HF.Mechtler C.Marschner C.Motz G.Kempe R. Inorg. Chem. 2006, 45: 1871 - 7b
Kempe R.Brenner S.Perdita A. Organometallics 1996, 15: 1071 - 7c
Kawasaki M.Suzuki Y.Terashima S. Chem. Lett. 1984, 239 - 8
Araki K.Mutai T.Shigemitsu Y.Yamada M.Nakajima T.Kuroda S.Shimao I. J. Chem. Soc., Perkin Trans. 2 1996, 613 - 9
Henrie RN. inventors; WO 8702665. ; Chem. Abstr. 1988, 109, 230807 - 10a
Lam PYS.Clark CG.Li R.Pinto DJP.Orwat MJ.Galemmo RA.Fevig JM.Teleha CA.Alexander RS.Smallwood AM.Rossi KA.Wright MR.Bai SA.He K.Luettgen JM.Wong PC.Knabb RM.Wexler RR. J. Med. Chem. 2003, 46: 4405 - 10b
Song YH.Clizbe L.Bhakta C.Teng W.Li W.Wong P.Huang B.Sinha U.Park G.Reed A.Scarborough RM.Zhu B.-Y. Bioorg. Med. Chem. Lett. 2002, 12: 2043 - 11a
Sakurai A.Midorikawa H. Bull. Chem. Soc. Jpn. 1968, 41: 430 - 11b
.
Agarwal N.Goel A.Ram VJ. J. Org. Chem. 2003, 68: 2983 - 11c
Brun EM.Gil S.Mestres R.Parra M. Synthesis 2000, 273 - 11d
Takaoka K.Aoyama T.Shioiri T. Tetrahedron Lett. 1996, 37: 4973 - 11e
Yin J.Xiang B.Huffman MA.Raab CE.Davies IW. J. Org. Chem. 2007, 72: 4554 - 11f
Goel A.Singh FV.Sharon A.Maulik PR. Synlett 2005, 623 - 11g
Teague SJ. J. Org. Chem. 2008, 73: 9765 - 11h
Hamper BC.Tesfu E. Synlett 2007, 2257 - 12a
Taylor EC.Corvetti AJ. J. Org. Chem. 1954, 19: 1633 - 12b
Gudmundsson KS.Johns BA. Org. Lett. 2003, 5: 1369 - 13
Chichibabin AE.Zeide OA. J. Russ. Phys. Chem. Soc. 1914, 46: 1216 - 14a
Basavaiah D.Rao AJ.Satyanarayana T. Chem. Rev. 2003, 103: 811 - 14b
Sing V.Batra S. Tetrahedron 2008, 64: 4511 - 14c
Lee KY.Gowrisankar S.Kim JN. Bull. Korean Chem. Soc. 2005, 26: 1481 - 14d
Basavaiah D.Rao PD.Hyma RS. Tetrahedron 1996, 52: 8001 - 14e
Shi Y.-L.Shi M. Eur. J. Org. Chem. 2007, 2905 - 14f
Masson G.Housseman C.Zhu J. Angew. Chem. Int. Ed. 2007, 46: 4614 - 15a
Narender P.Gangadasu B.Ravinder M.Srinivas U.Swamy GYSK.Ravikumar K.Jayathirtha Rao V. Tetrahedron 2006, 62: 954 - 15b
Narender P.Srinivas U.Ravinder M.Ramesh Ch.Ananda Rao B.Harakishore K.Gangadasu B.Murthy USN.Jayathirtha Rao V. Bioorg. Med. Chem. 2006, 14: 4600 - 15c
Narender P.Srinivas U.Gangadasu B.Biswas S.Jayathirtha Rao V. Bioorg. Med. Chem. Lett. 2005, 15: 5378 - 15d
Narender P.Ravinder M.Sadhu PS.Raju BC.Ramesh Ch.Jayathirtha Rao V. Helv. Chim. Acta 2009, 92: 959 - 15e
Ravinder M.Sadhu PS.Jayathirtha Rao V. Tetrahedron Lett. 2009, 50: 4229 - 16a
Gangadasu B.Narender P.Bharath Kumar S.Ravinder M.Ananda Rao B.Ramesh Ch.Raju BC.Jayathirtha Rao V. Tetrahedron 2006, 62: 8398 - 16b
Sadhu PS.Ravinder M.Arun Kumar P.Jayathirtha Rao V. Photochem. Photobiol. Sci. 2009, 8: 513 - 16c
Gangadasu B.Janaki Ram Reddy M.Ravinder M.Bharath Kumar S.Raju BC.Pranay Kumar K.Murthy USN.Jayathirtha Rao V. Eur. J. Med. Chem. 2009, 44: 4661 - 17a
Basavaiah D.Gowriswari VVL. Synth. Commun. 1987, 17: 587 - 17b
Cai J.Zhou Z.Zhao G.Tang C. Org. Lett. 2002, 4: 4723 - 17c
Suárez M.Armas MD.Ramírez O.Alvarez A.Alvarez RM.Molero D.Seoane C.Liz R.Armas HND.Blaton NM.Peeters OM.Martín N. New J. Chem. 2005, 29: 1567 - 17d
Cho H.Ueda M.Mizuno A.Ishihara T.Aisaka K.Noguchi T. Chem. Pharm. Bull. 1989, 37: 2117 - 19a
SAINT (Version 6.28a) and SMART (Version 5.625)
Bruker
AXS Inc.;
Madison USA:
2001.
- 19b
Sheldrick GM. SHELXS-97 and SHELXL-97 Programs for Crystal Structure Solution and Refinement University of Göttingen; Germany: 1997. - 19c
Nardelli M. J. Appl. Crystallogr. 1995, 28: 659 - 19d
Spek AL. J. Appl. Crystallogr. 2003, 36: 7
References
X-ray crystallographic data for compound 3a have been deposited at The Cambridge Crystallographic Data Centre (CCDC no. 734177). These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or on application to The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk.
- 1a
Scriven EFV. In Comprehensive Heterocyclic Chemistry Part 2, Vol. 2:Boulton AJ.McKillop A. Pergamon; New York: 1984. p.165-314 - 1b
Leffler MT. Org. React. 1942, 1: 91 - 1c
McGill CK.Rappa A. Adv. Heterocycl. Chem. 1988, 44: 1 - 1d
Landriscina M.Prudovsky I.Carreira CM.Soldi R.Tarantini F.Maciag T. J. Biol. Chem. 2000, 275: 32753 - 1e
Henry GD. Tetrahedron 2004, 60: 6043 - 1f
Scipione L.De Vita D.Musella A.Flammini L.Bertoni S.Barocelli E. Bioorg. Med. Chem. Lett. 2008, 18: 309 - 1g
Lawton GR.Ranaivo HR.Chico LK.Ji H.Xue F.Martásek P.Roman LJ.Watterson M.Silverman RB. Bioorg. Med. Chem. 2009, 17: 2371 - 1h
Lechat P.Tesleff S.Bownan WC. Aminopyridines and Similarly Acting Drugs Pergamon; Oxford: 1982. - 1i
Zhang J.Pettersson HI.Huitema C.Niu C.Yin J.James MNG.Eltis LD.Vederas JC. J. Med. Chem. 2007, 50: 1850 - 2a
Cocco MT.Congiu C.Lilliu V.Onnis V. Bioorg. Med. Chem. 2007, 15: 1859 - 2b
Amr A.-GE.Mohamed AM.Mohamed SF.Abdel-Hafez NA.Hammam AE.- FG. Bioorg. Med. Chem. 2006, 14: 5481 - 2c
Girgis AS.Kalmouch A.Ellithey M. Bioorg. Med. Chem. 2006, 14: 8488 - 2d
Murata T.Shimada M.Sakakibara S.Yoshino T.Masuda T.Shintani T.Sato H.Koriyama Y.Fukushima K.Nunami N.Yamauchi M.Fuchikami K.Komura H.Watanabe A.Ziegelabauer KB.Bacon KB.Lowinger TB. Bioorg. Med. Chem. Lett. 2004, 14: 4019 - 2e
Kuramochi T.Kakefuda A.Yamada H.Tsukamoto I.Taguchi T.Sakamoto S. Bioorg. Med. Chem. 2005, 13: 4022 - 3a
Dormer PG.Eng KK.Farr RN.Humphrey GR.McWilliams JC.Reider PJ.Sager JW.Volante RP. J. Org. Chem. 2003, 68: 467 - 3b
Hamada Y.Takeuchi I. Chem. Pharm. Bull. 1971, 19: 1857 - 3c
Zhichkin P.Beer CMC.Rennells WM.Fairfax DJ. Synlett 2006, 379 - 3d
Hsiao Y.Rivera NR.Yasuda N.Hughes DL.Reider PJ. Org. Lett. 2001, 3: 1101 - 4a
Cottineau B.O’Shea DF. Tetrahedron Lett. 2005, 46: 1935 - 4b
Ujjainwalla F.Walsh TF. Tetrahedron Lett. 2001, 42: 6441 - 5a
Myllymäki MJ.Koskinen AMP. Tetrahedron Lett. 2007, 48: 2295 - 5b
Bemis JE.Vu CB.Xie R.Nunes JN.Ng PY.Disch JS.Milne JC.Carney DP.Lynch AV.Jin L.Smith JJ.Lavu S.Iffland A.Jirousek MR.Perni RB. Bioorg. Med. Chem. Lett. 2009, 19: 2350 - 6a
Andaloussi M.Moreau E.Chavignon O.Teulade JC. Tetrahedron Lett. 2007, 48: 8392 - 6b
Hamama WS.Zoorob HH. Tetrahedron 2002, 58: 6143 - 6c
Adib M.Sheibani E.Zhu L.-G.Mirzaei P. Tetrahedron Lett. 2008, 49: 5108 - 7a
Deeken S.Proch S.Casini E.Braun HF.Mechtler C.Marschner C.Motz G.Kempe R. Inorg. Chem. 2006, 45: 1871 - 7b
Kempe R.Brenner S.Perdita A. Organometallics 1996, 15: 1071 - 7c
Kawasaki M.Suzuki Y.Terashima S. Chem. Lett. 1984, 239 - 8
Araki K.Mutai T.Shigemitsu Y.Yamada M.Nakajima T.Kuroda S.Shimao I. J. Chem. Soc., Perkin Trans. 2 1996, 613 - 9
Henrie RN. inventors; WO 8702665. ; Chem. Abstr. 1988, 109, 230807 - 10a
Lam PYS.Clark CG.Li R.Pinto DJP.Orwat MJ.Galemmo RA.Fevig JM.Teleha CA.Alexander RS.Smallwood AM.Rossi KA.Wright MR.Bai SA.He K.Luettgen JM.Wong PC.Knabb RM.Wexler RR. J. Med. Chem. 2003, 46: 4405 - 10b
Song YH.Clizbe L.Bhakta C.Teng W.Li W.Wong P.Huang B.Sinha U.Park G.Reed A.Scarborough RM.Zhu B.-Y. Bioorg. Med. Chem. Lett. 2002, 12: 2043 - 11a
Sakurai A.Midorikawa H. Bull. Chem. Soc. Jpn. 1968, 41: 430 - 11b
.
Agarwal N.Goel A.Ram VJ. J. Org. Chem. 2003, 68: 2983 - 11c
Brun EM.Gil S.Mestres R.Parra M. Synthesis 2000, 273 - 11d
Takaoka K.Aoyama T.Shioiri T. Tetrahedron Lett. 1996, 37: 4973 - 11e
Yin J.Xiang B.Huffman MA.Raab CE.Davies IW. J. Org. Chem. 2007, 72: 4554 - 11f
Goel A.Singh FV.Sharon A.Maulik PR. Synlett 2005, 623 - 11g
Teague SJ. J. Org. Chem. 2008, 73: 9765 - 11h
Hamper BC.Tesfu E. Synlett 2007, 2257 - 12a
Taylor EC.Corvetti AJ. J. Org. Chem. 1954, 19: 1633 - 12b
Gudmundsson KS.Johns BA. Org. Lett. 2003, 5: 1369 - 13
Chichibabin AE.Zeide OA. J. Russ. Phys. Chem. Soc. 1914, 46: 1216 - 14a
Basavaiah D.Rao AJ.Satyanarayana T. Chem. Rev. 2003, 103: 811 - 14b
Sing V.Batra S. Tetrahedron 2008, 64: 4511 - 14c
Lee KY.Gowrisankar S.Kim JN. Bull. Korean Chem. Soc. 2005, 26: 1481 - 14d
Basavaiah D.Rao PD.Hyma RS. Tetrahedron 1996, 52: 8001 - 14e
Shi Y.-L.Shi M. Eur. J. Org. Chem. 2007, 2905 - 14f
Masson G.Housseman C.Zhu J. Angew. Chem. Int. Ed. 2007, 46: 4614 - 15a
Narender P.Gangadasu B.Ravinder M.Srinivas U.Swamy GYSK.Ravikumar K.Jayathirtha Rao V. Tetrahedron 2006, 62: 954 - 15b
Narender P.Srinivas U.Ravinder M.Ramesh Ch.Ananda Rao B.Harakishore K.Gangadasu B.Murthy USN.Jayathirtha Rao V. Bioorg. Med. Chem. 2006, 14: 4600 - 15c
Narender P.Srinivas U.Gangadasu B.Biswas S.Jayathirtha Rao V. Bioorg. Med. Chem. Lett. 2005, 15: 5378 - 15d
Narender P.Ravinder M.Sadhu PS.Raju BC.Ramesh Ch.Jayathirtha Rao V. Helv. Chim. Acta 2009, 92: 959 - 15e
Ravinder M.Sadhu PS.Jayathirtha Rao V. Tetrahedron Lett. 2009, 50: 4229 - 16a
Gangadasu B.Narender P.Bharath Kumar S.Ravinder M.Ananda Rao B.Ramesh Ch.Raju BC.Jayathirtha Rao V. Tetrahedron 2006, 62: 8398 - 16b
Sadhu PS.Ravinder M.Arun Kumar P.Jayathirtha Rao V. Photochem. Photobiol. Sci. 2009, 8: 513 - 16c
Gangadasu B.Janaki Ram Reddy M.Ravinder M.Bharath Kumar S.Raju BC.Pranay Kumar K.Murthy USN.Jayathirtha Rao V. Eur. J. Med. Chem. 2009, 44: 4661 - 17a
Basavaiah D.Gowriswari VVL. Synth. Commun. 1987, 17: 587 - 17b
Cai J.Zhou Z.Zhao G.Tang C. Org. Lett. 2002, 4: 4723 - 17c
Suárez M.Armas MD.Ramírez O.Alvarez A.Alvarez RM.Molero D.Seoane C.Liz R.Armas HND.Blaton NM.Peeters OM.Martín N. New J. Chem. 2005, 29: 1567 - 17d
Cho H.Ueda M.Mizuno A.Ishihara T.Aisaka K.Noguchi T. Chem. Pharm. Bull. 1989, 37: 2117 - 19a
SAINT (Version 6.28a) and SMART (Version 5.625)
Bruker
AXS Inc.;
Madison USA:
2001.
- 19b
Sheldrick GM. SHELXS-97 and SHELXL-97 Programs for Crystal Structure Solution and Refinement University of Göttingen; Germany: 1997. - 19c
Nardelli M. J. Appl. Crystallogr. 1995, 28: 659 - 19d
Spek AL. J. Appl. Crystallogr. 2003, 36: 7
References
X-ray crystallographic data for compound 3a have been deposited at The Cambridge Crystallographic Data Centre (CCDC no. 734177). These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or on application to The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk.
Figure 1 ORTEP diagram of compound 3a
Scheme 1