3.1.4. Synthesis of Methyl 7-Oxo-7H-Thiazolo[3,2-a]Pyrimidine-5-Carboxylate Derivatives (13j, 19a–b, 20 and 5) Method A (2-CR)

In a round-bottomed flask equipped with a magnetic stirrer bar, DMAD/DEtAD (2) was added to the mixture of 2-aminothiazole derivative (11a–h) or 2-imino-1,3-oxazolidine (17) or 1H-1,2,4-triazol-5-amine (18) or 1H-1,2,4-triazole-5-thiol (5) in ethanol. The reaction mixture was allowed to reflux for 12–15 h while being monitored by TLC. After completion, the reaction was cooled and the solvent was removed under reduced pressure to obtain a residue which was washed with cold ethanol and filtered to give solid product.

N-(tert-butyl)-7-oxo-5H-thiazolo[3,2-a]pyrimidine-5-carboxylate (13j). Thiazol-2-amine (11a) (0.20 g, 1.99 mmol), di-tert-butyl acetylenedicarboxylate (DTAD) (2c) (0.45 g, 1.99 mmol); Physical properties: yellow solid; Yield: 0.36 g, 72%; Mp:246–248 °C; R_f 0.5, hexane/ethyl acetate (40%:60%); ¹H NMR (400 MHz, DMSO-d6) 8.29 (1H, d, J = 4.4 Hz, H-2), 7.34 (1H, d, J = 5.2 Hz, H-3), 6.73 (1H, s, H-6), 1.57 (9H, s, ((CH₃)₃); ¹³C NMR (101 MHz, DMSO-d6) δ 166.8 (C=O), 166.2 (C=O), 159.3 (C-9), 137.4 (C-5), 124.5 (C-2), 114.2 (C-6), 109.9 (C-3), 85.0 (C(CH₃)₃), 27.4 ((CH₃)₃); FTIR νmax/cm⁻¹: 2923, 1729, 1639; HRMS (ESI–TOF) m/z: [M + H]⁺ calculated for C₁₁H₁₃N₂O₃S⁺ 253.0641, found 253.0642.

Methyl 5-oxo-3,5-dihydro-2H-oxazolo[3,2-a]pyrimidine-7-carboxylate (19a); 2-imino-1,3-oxazolidine (0.51 g, 5.8 mmol) and DMAD (2a) (0.83 g, 5.8 mmol); Physical properties: White solid; Yield: 0.95 g, 82%; Mp: 251–253 °C; R_f 0.5, ethyl acetate (100 %); ¹H NMR (400 MHz, DMSO-d6) 6.37 (1H, s, H-6) 4.67 (2H, t, J = 8.4 Hz, CH₂), 4.49 (2H, t, J = 8.4 Hz, CH₂), 3.87 (3H, s, O-CH₃); ¹³C NMR (101 MHz, DMSO-d6) δ 170.9, (C=O) 162.1 (C=O), 160.8 (C-9), 138.1 (C-7), 110.9 (C-6), 66.6 (CH₂), 53.5 (O-CH₃), 47.03 (CH₂); FTIR νmax/cm⁻¹: 2965, 1732, 1624, 1535, 1476, 1421; HRMS (ESI–TOF) m/z: [M + H]⁺ calculated for C₈H₉N₂O₄⁺ 197.0557, found 197.0549.

Ethyl 5-oxo-3,5-dihydro-2H-oxazolo[3,2-a]pyrimidine-7-carboxylate (19b); 2-imino-1,3-oxazolidine (0.51 g, 5.8 mmol) and DEtAD (2b) (0.98 g, 5.8 mmol). Physical properties: White solid: Yield 0.98 g, 80%; Mp: 297–299 °C; R_f 0.5, ethyl acetate (100%); ¹H NMR (400 MHz, DMSO-d6) 5.64 (1H, s, H-6), 4.27 (2H, q, J = 7.2 Hz, O-CH₂), 4.04 (2H, t, J = 6.0 Hz, CH₂), 3.62 (2H, t, J = 5.6 Hz, CH₂), 1.27 (3H, t, J = 7.2 Hz, CH₃); ¹³C NMR (101 MHz, DMSO-d6) δ 170.4 (C=O) 163.2 (C=O), 161.6 (C-9), 155.7 (C-7), 89.5 (C-6), 61.1 (CH₂), 58.5 (CH₂), 48.1 (CH₂), 13.8 (CH₃); FTIR νmax/cm⁻¹: 3125, 2958, 1700, 1698, 1662, 1642, 1637, 1381; HRMS (ESI–TOF) m/z: [M + H]⁺ calculated for C₉H₁₁N₂O₄⁺ 211.0713, found 211.0708.

Ethyl 5-oxo-5,8-dihydro-[1,2,4]triazolo[4,3-a]pyrimidine-7-carboxylate (20); 1H-1,2,4-triazol-5-amine (0.50 g, 6.0 mmol) and DEtAD (2b) (1.02 g, 6.0 mmol). Physical properties: Brown solid: Yield: 1.1 g, 88%; Mp: 185–187 °C; R_f 0.5, ethyl acetate (100 %); ¹H NMR (400 MHz, DMSO-d6) 8.91 (1H, s, H-5), 6.66 (1H, s, H-7), 4.50 (2H, q, J = 6.8 Hz, O-CH₂), 1.40 (3H, t, J = 7.2 Hz, CH₃); ¹³C NMR (101 MHz, DMSO-d6) δ 160.5 (C=O), 158.9 (C=O), 151.9 (C-5), 134.1 (Ar-C), 132.9 (Ar-C) 112.9 (C-7), 62.5 (CH₂), 12.9 (CH₃); FTIR νmax/cm⁻¹: 3150, 3068, 2909, 2731, 1722, 1680, 1610, 1579; HRMS (ESI–TOF) m/z: [M + H]⁺ calculated for C₈H₉N₄O₃⁺ 209.0669, found 209.0677.

7-Oxo-7H-[1,2,4]triazolo[5,1-b][1,3]thiazine-5-carboxylate (5); 1H-1,2,4-Triazole-5-thiol (0.50 g, 5.0 mmol) and DEtAD (2b) (0.85 g, 5.0 mmol). Physical properties: White solid; Yield: 0.92 g, 82%; Mp: 110–112 °C; R_f 0.9 hexane/ethyl acetate (20%:80%); ¹H NMR (400 MHz, DMSO-d6) 8.68 (1H, s, H-4), 7.54 (1H, s, H-6), 4.48 (2H, q, J = 7.2 Hz, O-CH₂), 1.38 (3H, t, J = 6.8 Hz, CH₃); ¹³C NMR (101 MHz, DMSO-d6) δ 160.9 (C=O), 155.3 (C=O), 153.7 (C-4), 151.56 (C-2), 139.6 (C-7) 122.2 (C-6), 64.1 (CH₂), 13.8 (CH₃); FTIR νmax/cm⁻¹: 3123, 3053, 2987, 1698, 1582, 1491; HRMS (ESI–TOF) m/z: [M + H]⁺ calculated for C₈H₈N₃O₃S⁺ 226.0281, found 226.0288.