Ammonia → 7-Bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Reaction equation

Br[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:7]=1[C:13](=O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20])=[O:4].CO.[NH3:24]>>[Br:12][C:9]1[CH:10]=[CH:11][C:6]2[NH:5][C:3](=[O:4])[CH2:2][N:24]=[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[C:7]=2[CH:8]=1

Participants

Reactant 3

HCID 222Ammonia2×

HCID 887Methanol

HCID 534406762-Bromo-N-[4-bromo-2-(2-fluorobenzoyl)phenyl]acetamide

Product 1

HCID 129470247-Bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Procedure

The product from Step 1 (21.17 g, 51 mmol) was dissolved in ammonia, 2M in methanol (400 mL, 800 mmol) that was further saturated with anhydrous ammonia. The solution was heated to reflux for 16 hr overnight, and allowed to cool to room temperature. The solution was concentrated and the residue was dissolved in ethyl acetate and water. The ethyl acetate layer was washed twice with water, dried with brine, and concentrated to give a yellow solid. The solid was recrystallized from ethyl acetate/hexane to give a white powder that was washed with hexane and air dried (9.65 g, 56.8%).