m-Tolyl isocyanate → N-[(3RS)-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea

HRID 963513Notes

Reaction equation

HRID 963513 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]3[O:29][C:28](=[O:30])[CH:27]=[CH:26][C:25]=3[CH:31]=2)[C:3]1=[O:32].[CH3:33][C:34]1[CH:35]=[C:36]([N:40]=[C:41]=[O:42])[CH:37]=[CH:38][CH:39]=1>C(Cl)Cl>[F:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:7]1[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]3[O:29][C:28](=[O:30])[CH:27]=[CH:26][C:25]=3[CH:31]=2)[C:3](=[O:32])[CH:2]([NH:1][C:41]([NH:40][C:36]2[CH:37]=[CH:38][CH:39]=[C:34]([CH3:33])[CH:35]=2)=[O:42])[N:8]=1

Participants

4

Reactant 2

HCID 69303m-Tolyl isocyanateHCID 19081358(3RS)-3-amino-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-1H-1,4-benzodiazepin-2-one

Product 1

HCID 19081331N-[(3RS)-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)ureaYield 71.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3RS)-3-amino-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-1H-1,4-benzodiazepin-2-one (214 mg) in dry methylene chloride (20 ml) was added dropwise a solution of 3-methylphenyl isocyanate (73 mg) in dry methylene chloride (10 ml) under nitrogen atmosphere at cooling in an ice-bath. The mixture was stirred under the same temperature for 1 hour and at ambient temperature overnight. The resultant precipitates were collected by filtration to afford a crude product. The crude product was purified by column chromatography on silica gel with eluents of chloroform and a mixture of chloroform and ethyl acetate to afford N-[(3RS)-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-methylphenyl)urea as a colorless crystalline solid (200 mg).

Workup

  1. temperatureat cooling in an ice-bath
  2. customThe resultant precipitates
  3. filtrationwere collected by filtration
  4. customto afford a crude product
  5. customThe crude product was purified by column chromatography on silica gel with eluents of chloroform
  6. additiona mixture of chloroform and ethyl acetate

Sources & evidence

ORD record
ord-2fac923bd1c74af8a9e6a964a38d280e
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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