反应详情

温度

90 °C

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (328 mg, 1.00 mmol) was placed in a sealed tube with 4-amino-6-chloropyrimidine-5-carbonitrile (154.5 mg, 1.00 mol), DIPEA (0.7 mL, 4.00 mol) and IPA (1 mL). The tube was flushed with argon, sealed and the contents heated at 90° C. for 16 h. The cooled mixture was evaporated then diluted with EtOAc and water. The organic layer was washed with brine, dried (MgSO4) and evaporated. The crude residue was purified by chromatography on silica (Si—PCC, 1-80% EtOAc in DCM). The product containing fractions were pooled and evaporated almost to dryness. The residue was triturated in ether to afford 246 as a cream solid (240 mg, 65%). 1H NMR (CDCl3, 400 MHz): δ 8.01 (1H, s), 7.69 (1H, dd, J=8.8, 4.7 Hz), 7.59-7.49 (3H, m), 7.43-7.36 (2H, m), 7.02 (1H, td, J=9.2, 1.1 Hz), 6.77 (1H, dd, J=8.6, 2.4 Hz), 6.18 (1H, d, J=7.5 Hz), 5.52 (1H, quin, J=7.2 Hz), 5.30 (2H, br s), 1.54 (3H, d, J=6.9 Hz). LCMS (Method K): RT 3.80 min [M+H]+ 374

1. customThe tube was flushed with argon
2. customsealed
3. customThe cooled mixture was evaporated
4. additionthen diluted with EtOAc and water
5. washThe organic layer was washed with brine
6. dry with materialdried (MgSO4)
7. customevaporated
8. customThe crude residue was purified by chromatography on silica (Si—PCC, 1-80% EtOAc in DCM)
9. additionThe product containing fractions
10. customevaporated almost to dryness
11. customThe residue was triturated in ether