Synlett 2007(17): 2703-2706  
DOI: 10.1055/s-2007-991048
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel, One-Pot, Three-Component Synthesis of 5H-[1,3]Thiazolo[3,2-a]pyrimidine Derivatives

Mehdi Adib*a, Meisam Nosratia, Mohammad Mahdavia, Long-Guan Zhub, Peiman Mirzaeic
a School of Chemistry, University College of Science, University of Tehran, Tehran, Iran
Fax: +98(21)66495291; e-Mail: madib@khayam.ut.ac.ir;
b Chemistry Department, Zhejiang University, Hangzhou 310027, P. R. of China
c Department of Chemistry, Shahid Beheshti University, Tehran, Iran
Further Information

Publication History

Received 18 April 2007
Publication Date:
25 September 2007 (online)

Abstract

A novel synthesis of highly functionalized 5H-[1,3]thi­azolo[3,2-a]pyrimidines is described via a one-pot, three-component addition reaction between isocyanides, dialkyl acetylene-dicarboxylates and ethyl 2-oxo-2-(1,3-thiazol-2-ylamino)acetates in good yields.

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Procedure for the Preparation of Dimethyl 7-[Cyclo-hexyl(2-ethoxy-2-oxoacetyl)amino]-5 H -[1,3]thiazolo[3,2- a ]pyrimidine-5,6-dicarboxylate ( 4a): To a magnetically stirred solution of ethyl 2-oxo-2-(1,3-thiazol-2-yl-amino)acetate (0.200 g, 1 mmol) and dimethyl acetylene-dicarboxylate (0.142 g, 1 mmol) in anhyd CH2Cl2 (6 mL) was added dropwise a solution of cyclohexyl isocyanide (0.109 g, 1 mmol) in anhyd CH2Cl2 (2 mL) at 25 °C over 10 min. The reaction mixture was then stirred for 24 h. The solvent was removed and the residue was purified by column chromatography using n-hexane-EtOAc (1:2) as eluent. The solvent was removed and the product was obtained. Yield: 0.41 g (90%); yellow crystals. IR (KBr): 1744, 1725, 1680, 1657 (C=O), 1535, 1483, 1414, 1340, 1223, 1193, 1121 cm-1. 1H NMR (500.1 MHz, CDCl3): δ = 1.06-2.02 [t, J = 7.0 Hz, 3 H, OCH2CH 3; m, 10 H, CH(CH 2)5], 3.68, 3.69 (2 × s, 6 H, 2 × OMe), 4.05-4.25 [2 × dq, ABX3 system, 2 J = 10.6 Hz, 3 J = 7.0 Hz, 2 H, OCH A H BCH3; m, 1 H, NCH(CH2)5], 5.92 (s, 1 H, NCH), 6.61 (d, J = 4.6 Hz, 1 H, CH), 6.84 (d, J = 4.6 Hz, 1 H, CH). 13C NMR (125.8 MHz, CDCl3): δ = 13.78 (OCH2 CH3), 25.54, 26.04, 26.05, 28.63, 31.67 (5 × CH2), 51.83, 52.90 (2 × OMe), 56.78, 57.72 (2 × NCH), 61.60 (OCH2), 90.77 (NC=C), 107.90, 126.89 (2 × CH), 152.19, 161.38, 162.16, 165.07, 166.88, 168.23 (2 × C, 4 × C=O). MS: m/z (%) = 451 (<1) [M+], 432 (6), 374 (58), 318 (100), 244 (51), 216 (24), 199 (16), 172 (14), 145 (12), 78 (20), 57 (10). Anal. Calcd for C20H25N3O7S (451.50): C, 53.20; H, 5.58; N, 9.31. Found: C, 53.0; H, 5.7; N, 9.2. Di- tert -butyl 7-[Cyclo-hexyl(2-ethoxy-2-oxo-acetyl)amino]-3-methyl-5 H -[1,3]thiazolo[3,2- a ]pyrimi-dine-5,6-dicarboxylate (4f): yield: 0.46 g (84%); yellow crystals. IR (KBr): 1745, 1738, 1674, 1661 (C=O), 1556, 1489, 1416, 1391, 1354, 1317, 1225, 1153, 1097 cm-1. 1H NMR (300.1 MHz, CDCl3): δ = 1.09-2.03 [t, J = 7.1 Hz, 3 H, OCH2CH 3; 2 × s, 18 H, 2 × t-Bu; m, 10 H, CH(CH 2)5], 2.19 (s, 3 H, Me), 4.05-4.25 [m, 2 H, OCH AHBCH3, CH(CH2)5], 4.33 (dq, AB system, 2 J = 10.5 Hz, 3 J = 7.1 Hz, 1 H, OCHA H BCH3), 5.83 (s, 1 H, NCH), 6.16 (s, 1 H, CH). 13C NMR (75.5 MHz, CDCl3): δ = 13.68, 13.88 (Me, OCH2 CH3), 25.66, 25.88, 26.08 (3 × CH2), 27.91, 28.23 [2 × C(CH3)3], 28.60, 32.15 (2 × CH2), 55.16, 55.69 (2 × NCH), 61.90 (OCH2CH3), 81.56, 83.45 [2 × OC(CH3)3], 94.51 (N2C=C), 101.41 (CH), 135.51 (C), 150.22, 161.01, 162.21, 164.37, 166.89, 167.07 (2 × C, 4 × C=O). MS: m/z (%) = 549 (<1) [M+], 448 (50), 392 (51), 310 (21), 279 (14), 236 (51), 211 (52), 192 (13), 167 (34), 149 (100), 113 (10), 83 (22), 57 (26). Anal. Calcd for C27H39N3O7S (549.69): C, 59.00; H, 7.15; N, 7.64. Found: C, 58.8; H, 7.4; N, 7.5. Dimethyl 7-[ tert -Butyl(2-ethoxy-2-oxoacethyl)amino]-5 H -[1,3]thi-azolo[3,2- a ]pyrimidine-5,6-dicarboxylate (4g): yield: 0.36 g (85%); yellow crystals. IR (KBr): 1740, 1664 (C=O), 1483, 1367, 1329, 1232, 1200, 1086, 1013 cm-1. 1H NMR (300.1 MHz, CDCl3): δ = 1.24 (t, J = 7.2 Hz, 3 H, OCH2CH 3), 1.50 [s, 9 H, t-Bu], 3.72, 3.76 (2 × s, 6 H, 2 × OMe), 4.10, 4.21 (2 × dq, ABX3 system, 2 J = 10.5 Hz, 3 J = 7.2 Hz, 2 H, OCH A H BCH3), 5.95 (s, 1 H, NCH), 6.61 (d, J = 4.6 Hz, 1 H, CH), 6.86 (d, J = 4.6 Hz, 1 H, CH). 13C NMR (75.5 MHz, CDCl3): δ = 13.85 (OCH2 CH3), 28.08 [C(CH3)3], 51.80, 53.04 (2 × OMe), 57.91 (NCH), 60.56 [C(CH3)3], 61.40 (OCH2), 95.14 (N2C=C), 107.81, 126.82 (2 × CH), 151.56, 161.33, 162.19, 165.07, 166.47, 168.23 (2 × C, 4 × C=O). MS: m/z (%) = 425 (6) [M+], 366 (20), 310 (100), 296 (13), 264 (9), 250 (8), 236 (95), 211 (18), 176 (14), 167 (15), 149 (34), 57 (13). Anal. Calcd for C18H23N3O7S (425.46): C, 50.81; H, 5.45; N, 9.88. Found: C, 50.6; H, 5.6; N, 9.7. Diethyl 7-[ tert -Butyl(2-ethoxy-2-acetyl)amino]-3-methyl-5 H -[1,3]thiazolo[3,2- a ]pyr-imidine-5,6-dicarboxylate (4j): yield: 0.42 g (90%); yellow crystals. IR (KBr): 1738, 1685, 1663 (C=O), 1556, 1403, 1360, 1329, 1221, 1200, 1097, 1022 cm-1. 1H NMR (500.1 MHZ, CDCl3): δ = 1.21, 1.24, 1.32 (3 × t, J = 7.1 Hz, 9 H, 3 × OCH2CH 3), 1.49 [s, 9 H, t-Bu], 2.18 (d, 4 J = 1.1 Hz, 3 H, Me), 4.02-4.33 (m, 6 H, 3 × OCH 2CH3), 5.94 (s, 1 H, NCH), 6.16 (br q, 4 J = 1.1 Hz, 1 H, CH). 13C NMR (125.8 MHz, CDCl3): δ = 13.73, 13.84, 13.95, 14.29 (Me, 3 × OCH2 CH3), 28.21 [C(CH3)3], 55.45 (NCH), 60.56 [C(CH3)3], 61.13, 61.30, 62.25 (3 × OCH2CH3), 95.14 (N2C=C), 101.95 (CH), 135.20 (C), 150.17, 161.30, 162.10, 164.90, 167.24, 168.03 (2 × C, 4 × C=O). MS: m/z (%) = 467 (3) [M+], 394 (29), 338 (100), 264 (29), 236 (31), 192 (11), 167 (12), 149 (28), 57 (10). Anal. Calcd for C21H29N3O7S (467.54): C, 53.95; H, 6.25; N, 8.99. Found: C, 53.9; H, 6.4; N, 8.9.

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Selected X-ray Crystallographic Data for Compound 4a: C20H25N3O7S, monoclinic, space group = P21/n, a = 8.7880(9) Å, b = 20.488(2) Å, c = 12.2861(12) Å, β = 99.901(1)°, V = 2179.1(4) Å3, T = 295(2) K, Z = 4, D calcd = 1.376 g cm-3, µ(Mo-Kα) = 0.195 mm-1, 16164 reflections measured, 4061 unique reflections (R int = 0.032), 3284 observed reflections, final R 1 = 0.050, ωR 2 = 0.128 and for all data R 1 = 0.062. CCDC 640870 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.