反应详情

温度

85 °C

A mixture of the product of Step 4 (50 mg, 0.108 mmol), PdCl2(dppf) (as the dichloromethane adduct; 4.42 mg, 5.41 μmol) and Intermediate 1 (27.9 mg, 0.119 mmol) was degassed (alternating vacuum-N2 cycles). Dioxane (0.3 mL) and Na2CO3 (2.0 M, 162 μL, 0.325 mmol) were added. The mixture was degassed again and stirred at 85° C. for 2 hrs. The mixture was cooled to room temperature, diluted with ethyl acetate and gravity filtered on celite. After in vacuo concentration, the residue was purified by Chromatography on silica gel (0-100% ethyl acetate in hexanes) then briefly triturated in hexanes to give the 1-[5-(3-[(2,2,2-trifluoroethyl)amino]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol (36.4 mg, 0.074 mmol, 69% yield) as a white solid. MS ESI: [M+H]+ m/z 490.0. 1H NMR (500 MHz, CD3OD) δ 8.73 (d, J=4.9, 1H), 7.92 (s, 1H), 7.43 (s, 1H), 7.31 (s, 1H), 7.15 (d, J=4.9, 1H), 6.69 (s, 1H), 3.88 (q, 9.2, 2H), 2.79-2.67 (m, 2H), 2.67-2.36 (m, 2H), 2.12-1.92 (m, 2H).

1. customThe mixture was degassed again
2. temperatureThe mixture was cooled to room temperature
3. additiondiluted with ethyl acetate and gravity
4. filtrationfiltered on celite
5. concentrationAfter in vacuo concentration
6. customthe residue was purified by Chromatography on silica gel (0-100% ethyl acetate in hexanes)
7. customthen briefly triturated in hexanes