Hydrochloric Acid → HCID 178522526, compound

HRID 1769861Notes

Reaction equation

HRID 1769861 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[NH:15][C:14]1=[O:30])=[O:11].Cl.C([N:51]1[CH:55]=[C:54]([CH2:56]Cl)[N:53]=[CH:52]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].Cl>O.C(OCC)(=O)C.C(O)(=O)C.CN(C)C=O>[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]([CH2:56][C:54]2[N:53]=[CH:52][NH:51][CH:55]=2)[C:14]1=[O:30])=[O:11]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 14208192HCID 14208192, compoundHCID 18670783HCID 18670783, compound

Product 1

HCID 178522526HCID 178522526, compoundYield 32.3%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of-(3RS)-1,3-dihydro-3-(2-indolylcarbonylamino)-5-phenyl-2H-1,4-benzodiazepine-2-one (800 mg), 1-trityl-4-chloromethylimidazole hydrochloride (790 mg) and N,N-dimethylformamide (16 ml) was added sodium hydride (62% suspension in mineral oil, 168 mg) under stirring and cooling at 0 ° C. in an ice-bath. The mixture was stirred for 30 minutes at 0° to 5 ° C. and heated at 70° to 80° C. for 3.0 hours. To the cooled reaction mixture were added acetic acid (2.0 ml) and 6N hydrochloric acid (5 ml). The mixture was stirred for 1.0 hour at 60° C. The cooled reaction mixture was poured into a mixture of ethyl acetate (100 ml) and water (100 ml) under stirring. The organic layer was separated, washed with water three times, dried over magnesium sulfate and evaporated. The residue was chromatographed on silica gel with an eluent of a mixture of chloroform and methanol (20:1) to give (3RS)-1,3-dihydro-3-(2-indolylcarbonylamino )-1-(4-imidazolylmethyl)-5-phenyl-2H-1,4-benzodiazepine-2-one (306.0 mg).

Workup

  1. stirringThe mixture was stirred for 30 minutes at 0° to 5 ° C.
  2. temperatureheated at 70° to 80° C. for 3.0 hours
  3. customTo the cooled reaction mixture
  4. stirringThe mixture was stirred for 1.0 hour at 60° C
  5. customThe cooled reaction mixture
  6. stirringunder stirring
  7. customThe organic layer was separated
  8. washwashed with water three times
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. customThe residue was chromatographed on silica gel with an eluent of a mixture of chloroform and methanol (20:1)

Sources & evidence

ORD record
ord-59b90b55748d4facbcca0556632065d6
Source dataset
uspto-grants-1995_01
Patent number
US05382664

Reaction notes

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