反应详情

温度

55 °C

To the solution of 1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1-(pyrrolidin-3-yl)ethanol (20 mg, 0.044 mmol, 1:1 mix of diastereomers) in tetrahydrofuran (0.4 mL) was added potassium cyanate (25 mg, 0.308 mmol), water (1.2 mL) and HCl (2 M in water, 0.14 mL, 0.280 mmol). The mixture was stirred at 55° C. for 3 hours then cooled to room temperature. The mixture was purified on reversed phase HPLC (Sunfire prep C18 OBD 5 uM, acetonitrile/water+0.1% TFA) to afford 3-{1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]ethyl}pyrrolidine-1-carboxamide as a 1:1 mixture of diastereomers. MS ESI calc'd. for C22H23F3N6O2S [M+H]+ 493. found 493. 1H NMR (500 MHz, CD3OD) δ 8.65-8.60 (m, 1H, two sets of doublets overlap from two diastereomers), 8.39 (d, 1H, two singlets from two diastereomers), 7.86 (s, 1H), 7.51 (d, 1H, two singlets from two diastereomers), 7.46-7.42 (m, 1H, two sets of doublets overlap from two diastereomers), 7.05 (s, 1H), 3.65-2.82 (m, 5H, two sets of peaks from two diastereomers), 2.50 (s, 3H), 2.20-2.00 (m, 2H), 1.69 (s, 3H). rhSyk activity=+++.

1. temperaturethen cooled to room temperature
2. customThe mixture was purified on reversed phase HPLC (Sunfire prep C18 OBD 5 uM, acetonitrile/water+0.1% TFA)