反应详情

{4-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetic acid hydrochloride salt (31.5 mg, 0.47 mmol, example 99), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 19.7 mg, 0.052 mmol, Advchemtech), piperazin-2-one (12 mg, ) and triethylamine (0.05 mL) was mixed in dichloromethane (2 ml) and stirred for 2 h. The mixture was diluted with dichloromethane (5 mL) and was washed with sodium hydroxide (0.1 N solution), saturated sodium chloride solution and water. Dichloromethane solution was dried over anhydrous magnesium sulfate. The solids were filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by preparative HPLC (reversed phase, eluting with acetonitrile and water) gave the title compound (20.7 mg). HR-MS (ES, m/z) calculated for C39H48Cl2N7O4 [(M+H)+] 748.314, observed 748.3138.

1. washwas washed with sodium hydroxide (0.1 N solution), saturated sodium chloride solution and water
2. dry with materialDichloromethane solution was dried over anhydrous magnesium sulfate
3. filtrationThe solids were filtered off
4. concentrationthe filtrate was concentrated in vacuo
5. customPurification of the crude residue
6. washby preparative HPLC (reversed phase, eluting with acetonitrile and water)