Hydrochloric Acid → HCID 21266005, compound

HRID 566285Notes

Reaction equation

HRID 566285 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:17][NH:18][CH3:19])=[C:13]([CH2:15][OH:16])[N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:6]=2[CH:27]=1.Cl.O>O1CCOCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:17][NH:18][CH3:19])=[C:13]([CH2:15][OH:16])[N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:6]=2[CH:27]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 21265971HCID 21265971, compound

Product 1

HCID 21266005HCID 21266005, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

820 mg of tetrabromomethane and 650 mg of triphenylphosphine were added in succession and portionwise to a solution of 1.0 g of [2-(tert.-butyl-dimethyl-silanyloxymethyl)-8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-1-yl]methanol in 10 ml of tetrahydrofuran. After stirring at room temperature for 2 h. a further 160 mg of tetrabromomethane and 130 mg of triphenylphosphine were added and the mixture was stirred for a further 2 h. Subsequently, the solvent was removed at 40° C. in a vacuum and the residue was triturated twice with 10 ml of ethyl acetate each time and filtered off. The combined filtrates were added to 50 ml of a tetrahydrofuran solution saturated with methylamine at 0° C. and this reaction mixture was stirred at room temperature for 3 h. Then, all volatiles were removed in an oil pump vacuum at 40° C., the residue was taken up with 5 ml of tetrahydrofuran and 10 ml of 1N hydrochloric acid and stirred at room temperature for 3 h. After the addition of 30 ml of ethyl acetate the separated organic phase was again extracted with 10 ml of 1N hydrochloric acid. The combined aqueous phases were treated with 10 ml of 2N sodium hydroxide solution and extracted three times with 30 ml of ethyl acetate each time. Drying of the organic phase over magnesium sulphate and removal of the solvent in a vacuum yielded 600 mg of crude product which was purified by chromatography on 50 g of silica gel with a mixture of dichloromethane/ methanol/ammonium hydroxide 200:10:1. 290 mg (37%) of 8-chloro-6-(2-fluorophenyl)-1-methylaminomethyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol were isolated as a crystalline foam. After recrystallization from dichloromethane/diethyl ether the m.p. lay at 172° C. For the preparation of the hydrochloride, 196 mg (0.509 mmol) of this product were dissolved in 5 ml of dioxan and 4.85 ml of 0.1N hydrochloric acid were added dropwise. The mixture was lyophilized, taken up with 20 ml of water, filtered and again lyophilized and there was thus isolated 8-chloro-6-(2-fluorophenyl)-1-methylaminomethyl-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol hydrochloride (1:1) of m.p. 1500° C. (dec.).

Workup

  1. customAfter recrystallization from dichloromethane/diethyl ether the m.p.
  2. customlay at 172° C
  3. filtrationfiltered

Sources & evidence

ORD record
ord-65cdc570b6ae46f58297ab5053f83bec
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

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