反应详情

TBAF (1 M, 3.71 μL, 3.71 μmol) was added to a stirred, cooled (0° C.) mixture of cyclopropyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methanone (29 mg, 0.074 mmol) and (trifluoromethyl)trimethylsilane (14.24 μL, 0.089 mmol) in tetrahydrofuran (0.2 mL) and the mixture was stirred at room temperature for 4 h. Additional TMSCF3 (20 μL) and tetramethyammonium fluoride (0.811 mg, 7.43 μmol) were added and the mixture was left to stir overnight. Additional TMSCF3 (22 μL) and KOtBu (1M in TIM, 74 μL) were added to the mixture and left to stir for 2 days. The mixture was treated with TBAF (74 μL), ether and HCl, and extracted with ethyl acetate. The combined organics were concentrated, and purified by flash chromatography to give 1-cyclopropyl-2,2,2-trifluoro-1-[5-(3-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol (23 mg, 0.050 mmol, 67.2% yield). APCI: [M+H]+ m/z 461.1. 1H NMR (400 MHz, CDCl3): δ 8.72 (d, J=4.9 Hz, 1H); 8.19 (s, 1H); 7.97 (s, 1H); 7.52 (d, J=8.3 Hz, 1H); 7.48-7.40 (m, 2H); 7.32 (d, J=7.8 Hz, 1H); 7.12 (d, J=4.9 Hz, 1H); 4.53 (s, 1H); 1.58-1.51 (m, 1H); 1.01-0.94 (m, 1H); 0.77-0.67 (m, 1H); 0.59-0.51 (m, 2H). rhSYK activity=+++

1. temperaturecooled
2. waitthe mixture was left
3. stirringto stir overnight
4. waitleft
5. stirringto stir for 2 days
6. extractionextracted with ethyl acetate
7. concentrationThe combined organics were concentrated
8. custompurified by flash chromatography