Hydrochloric Acid → (RS)-N-(2,3-Dihydro-1-(2-hydroxyethyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-1H-indole-2-carboxamide

HRID 258091Notes

Reaction equation

HRID 258091 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:12][CH:13]1[N:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]2[CH:26]=[CH:27][CH:28]=[CH:29][C:16]=2[N:15]([CH2:30][CH2:31][O:32]C2CCCCO2)[C:14]1=[O:39])=[O:11].Cl.O>CC(C)=O>[OH:32][CH2:31][CH2:30][N:15]1[C:16]2[CH:29]=[CH:28][CH:27]=[CH:26][C:17]=2[C:18]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[N:19][CH:13]([NH:12][C:10]([C:2]2[NH:1][C:9]3[C:4]([CH:3]=2)=[CH:5][CH:6]=[CH:7][CH:8]=3)=[O:11])[C:14]1=[O:39]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 14800305(3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-1-{2-((RS)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2-one2×

Product 1

HCID 14800306(RS)-N-(2,3-Dihydro-1-(2-hydroxyethyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-1H-indole-2-carboxamideYield 79.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a suspension of a mixture (0.42 g)of (3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-1 -{2-((RS)-2-tetrahydropyranyloxy)ethyl}-2H-1,4-benzodiazepine-2-one and (3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-1-{2-((SR)-2-tetrahydropyranyloxy) ethyl}-2H-1,4-benzodiazepine-2-one in acetone (10 ml) was added 6N-hydrochloric acid (0.4 ml) under stirring at ambient temperature. After the yellow clear solution was stirred for 45 minutes, the additional 6N-hydrochloric acid (0.4 ml) and water (1 ml) were added thereto. The mixture was stirred for 0.5 hour at ambient temperature. Neutralization with an aqueous solution of sodium bicarbonate and removal of acetone gave yellow precipitates, which were collected by filtration, washed with water and dried. The crude product was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate (5:1) to afford pure (3RS)-1,3-dihydro-1-(2-hydroxyethyl)-3-(2-indolylcarbonylamino)-5-phenyl-2H-1,4-benzodiazepine-2-one (0.28 g) as an amorphous. This was triturated in diethyl ether to give light yellow powder.

Workup

  1. stirringAfter the yellow clear solution was stirred for 45 minutes
  2. stirringThe mixture was stirred for 0.5 hour at ambient temperature
  3. customNeutralization with an aqueous solution of sodium bicarbonate and removal of acetone
  4. customgave yellow precipitates, which
  5. filtrationwere collected by filtration
  6. washwashed with water
  7. customdried
  8. customThe crude product was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate (5:1)

Sources & evidence

ORD record
ord-583611d74b1b428987dc7da820ef8433
Source dataset
uspto-grants-1993_11
Patent number
US05264433

Reaction notes

Loading…