反应详情

温度

50 °C

A solution of 4-methyl-2-thiazol-2-yl-pyrimidine-5-carboxylic acid (300 mg, 1.36 mmol) and 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (325 mg, 1.38 mmol) in DMF (5 mL) is stirred at 50° C. for 1 h. The mixture is treated with DMTMM (380 mg, 1.38 mmol) and stirred at 50° C. for 2 h. The mixture is diluted with saturated aqueous Na2CO3 (50 mL), and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0%-7% MeOH in DCM to afford 4-methyl-2-thiazol-2-yl-pyrimidine-5-carboxylic acid [5-fluoro-3-(3-hydroxy-3-methyl-butyl)-indol-1-yl]-amide (155 mg, 26%). MS: 440 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.22 (s, 1H), 8.14 (d, 1H), 8.08 (d, 1H), 7.40 (m, 3H), 7.06 (m, 1H), 4.31 (s, OH, 1H), 2.76 (s, 3H), 2.71 (m, 2H), 1.77 (m, 2H), 1.20 (s, 6H). IC50=5 nM.

1. extractionextracted with EtOAc (3×50 mL)
2. dry with materialThe combined organic layer is dried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue is purified by silica gel chromatography
6. washeluting with 0%-7% MeOH in DCM