Water → methyl 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-carboxylate

HRID 566282Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][CH:13]([C:18](=O)[CH3:19])[C:14]([O:16][CH3:17])=[O:15])[CH2:9][N:8]=[C:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[C:6]=2[CH:28]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:18]([CH3:19])=[C:13]([C:14]([O:16][CH3:17])=[O:15])[N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[C:6]=2[CH:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

1.40 g of methyl 2-[7-chloro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2-ylamino]-3-oxo-butyrate were taken up in 10 ml of dimethylformamide, 100 mg of p-toluenesulphonic acid monohydrate were added and the mixture was stirred at 80° C. for 2 h. For the working up the mixture was treated with 30 ml of water and extracted 5 times with 50 ml of diethyl ether each time. The combined organic phases were dried over magnesium sulphate, concentrated in a vacuum and purified by chromatography on 70 g of silica gel with dichloromethane containing 2% methanol. There were obtained 550 mg (41%) of methyl 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-carboxylate of m.p. 137-138° C. which was used without further purification for the step described below.

Workup

extractionextracted 5 times with 50 ml of diethyl ether each time
dry with materialThe combined organic phases were dried over magnesium sulphate
concentrationconcentrated in a vacuum
custompurified by chromatography on 70 g of silica gel with dichloromethane containing 2% methanol

Sources & evidence

ORD record: ord-47296b5807d84bf58ad0196d48d908a6
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06174881B1

Reaction notes

Loading…