Potassium Hydroxide → 2-[2-(4-methyl-1-piperazinyl)ethylthio]-5-phenyl-7-chloro-3H-1,4-benzodiazepine difumarate

HRID 839293Notes

Reaction equation

HRID 839293 reaction equation
[C:1]1([C:7]2[C:13]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[S:19])[CH2:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].Cl.Cl.Cl[CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]1.[C:34]([OH:41])(=[O:40])/[CH:35]=[CH:36]/[C:37]([OH:39])=[O:38]>[Cl-].[Na+].C(O)C.O1CCCC1>[C:34]([OH:41])(=[O:40])/[CH:35]=[CH:36]/[C:37]([OH:39])=[O:38].[C:34]([OH:41])(=[O:40])/[CH:35]=[CH:36]/[C:37]([OH:39])=[O:38].[CH3:33][N:30]1[CH2:31][CH2:32][N:27]([CH2:26][CH2:25][S:19][C:10]2[CH2:9][N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:13]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=3[N:11]=2)[CH2:28][CH2:29]1

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 444972Fumaric AcidHCID 826706ThionordiazepamHCID 111839401-(2-Chloroethyl)-4-methylpiperazine dihydrochloride

Product 1

HCID 706260212-[2-(4-methyl-1-piperazinyl)ethylthio]-5-phenyl-7-chloro-3H-1,4-benzodiazepine difumarateYield 51.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 5234Sodium ChlorideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 5.7 g of 1,3-dihydro-5-phenyl-7-chloro-2H-1,4-benzodiazepine-2-thione in a solvent mixture comprising 57 ml of a 10% aqueous potassium hydroxide solution and 6 ml of tetrahydrofuran is added at room temperature with stirring 7.0 g of 1-chloro-2-(4-methyl-1-piperazinyl)ethane dihydrochloride, and the resulting mixture is stirred at 40° C. for 4 hours. The reaction mixture is diluted with an aqueous sodium chloride solution and then extracted with ethyl acetate. The extract is washed with water and dried over magnesium sulfate, and the solvent is removed by distillation under reduced pressure. An oily product obtained as the residue is dissolved in ethyl alcohol and added with 3.8 g of fumaric acid, and the solvent is distilled off under reduced pressure to obtain a crystalline product. Recrystallization from tetrahydrofuran to obtain 5.4 g of 2-[2-(4-methyl-1-piperazinyl)ethylthio]-5-phenyl-7-chloro-3H-1,4-benzodiazepine difumarate, m.p. 193°-194° C. (decomposition), yield 42%.

Workup

  1. additionis added at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe extract is washed with water
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent is removed by distillation under reduced pressure
  6. customAn oily product obtained as the residue
  7. distillationthe solvent is distilled off under reduced pressure
  8. customto obtain a crystalline product
  9. customRecrystallization from tetrahydrofuran

Sources & evidence

ORD record
ord-bb0f7dfabc3d4a368241e4ef8a739ea5
Source dataset
uspto-grants-1978_06
Patent number
US04094870

Reaction notes

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