Allylamine → HCID 21265966, compound

3.07 g of tetrabromomethane and 2.43 g (9.3 mmol) of triphenylphosphine were added in succession and portionwise to a solution of 3.0 g of [2-(tert.-butyl-dimethylsilanyloxymethyl)-8-chloro-6-(2-fluoro-phenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]methanol in 10 ml of tetrahydrofuran. After stirring at room temperature for 3 h. the mixture was filtered and the residue was rinsed with a small amount of tetrahydrofuran. 25 ml (333 mmol) of allylamine were added to the filtrate and this reaction mixture was stirred at 50° C. for 2 h. Then, all volatiles were removed at 40° C. in an oil pump vacuum, the residue was taken up with 30 ml of tetrahydrofuran and 30 ml of 1N hydrochloric acid and stirred at room temperature for 3 h. After the addition of 100 ml of ethyl acetate the separated organic phase was again extracted with 30 ml of 1N hydrochloric acid. The combined aqueous phases were treated with 30 ml of 2N sodium hydroxide solution and extracted three times with 100 ml of ethyl acetate each time. Drying of the organic phase over magnesium sulphate and removal of the solvent in a vacuum yielded 2.6 g of crude product which was purified by chromatography on 300 g of silica gel with a mixture of dichloromethane/methanol/ammonium hydroxide 200:10:1. 1.96 g (77%) of 1-allylaminomethyl-8-chloro-6-(2-fluorophenyl)-4H-imidazo [1,2-a][1,4]benzodiazepine-2-methanol were thus isolated as a crystalline foam. After recrystallization from dichloromethane/diethyl ether the melting point lay at 173° C. For the preparation of the hydrochloride, 776 mg of this product were dissolved in 30 ml of dioxan and 18.9 ml of 0.1N hydrochloric acid were added dropwise. The mixture was lyophilized, taken up with 10 ml of water, filtered, again lyophilized and there was thus obtained 1-allylaminomethyl-8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol hydrochloride (1:1) of m.p. 140° C.

1. filtrationwas filtered
2. washthe residue was rinsed with a small amount of tetrahydrofuran
3. stirringthis reaction mixture was stirred at 50° C. for 2 h
4. customThen, all volatiles were removed at 40° C. in an oil pump vacuum
5. stirringstirred at room temperature for 3 h
6. additionAfter the addition of 100 ml of ethyl acetate the separated organic phase
7. extractionwas again extracted with 30 ml of 1N hydrochloric acid
8. additionThe combined aqueous phases were treated with 30 ml of 2N sodium hydroxide solution
9. extractionextracted three times with 100 ml of ethyl acetate each time
10. dry with materialDrying of the organic phase over magnesium sulphate and removal of the solvent in a vacuum
11. customyielded 2.6 g of crude product which
12. customwas purified by chromatography on 300 g of silica gel with a mixture of dichloromethane/methanol/ammonium hydroxide 200:10:1

ORD record

ord-761789a6ea4749d0867013e89d367666

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06174881B1