反应详情

温度

50 °C

Trifluoroacetate salt of 4′-Methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-amine, prepared as in Step II of Example 36, described above, (150 mg; 0.35 mmol; 1 eq.) is suspended in DCM (5 ml). N,N-Diisopropylethylamine (133 μl; 0.78 mmol; 2.20 eq.) is added. A solution of ethyl 2-isocyanatopropionate (Aldrich)(50.6 mg; 0.35 mmol; 1 eq.) in DCM (3 ml) is added and the resulting mixture is heated at 50° C. overnight. EtOAc is added (10 ml) and the mixture is washed with water. Organic phase is dried over MgSO4 and concentrated. The crude mixture is resubmitted to the same reaction conditions. After one night at 50° C., the conversion is complete and a similar work-up is performed. The crude product is recrystallized in MeOH, affording Compound (37) as white-off powder (92.2 mg; 58%). 1H NMR (DMSO-d6, 300 MHz) δ 1.18 (t, J=6 Hz, 3H), 2.41 (s, 3H), 2.50 (m, 2H), 3.36 (m, 2H), 3.68 (m, 6H), 4.07 (q, J=6 Hz, 2H), 4.33 (m, 2H), 6.70 (br s, 1H), 7.90 (s, 1H), 10.52 (br s, 1H). M− (ESI): 452.14; M+ (ESI): 454.11. HPLC (method A), Rt: 2.89 min (purity: 98.9%).

1. washthe mixture is washed with water
2. dry with materialOrganic phase is dried over MgSO4
3. concentrationconcentrated
4. customThe crude mixture is resubmitted to the same reaction conditions
5. waitAfter one night at 50° C.
6. customThe crude product is recrystallized in MeOH