Water → N-[(3RS)-1-{(3-azabicyclo[3.2.2]non-3-yl)-carbonylmethyl}-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-trifluoromethylphenyl)urea

HRID 963516

Reaction equation

HRID 963516 reaction equation
[CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:10]([CH2:12][N:13]1[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])=[N:16][CH:15]([NH2:31])[C:14]1=[O:32])=[O:11])[CH2:2]2.[F:33][C:34]([F:55])([F:54])[C:35]1[CH:36]=[C:37]([NH:41][C:42](=O)[O:43]C2C=CC([N+]([O-])=O)=CC=2)[CH:38]=[CH:39][CH:40]=1.C(N(CC)CC)C.O>CN(C)C=O.C(OC(C)C)(C)C>[CH:5]12[CH2:8][CH2:9][CH:1]([CH2:7][CH2:6]1)[CH2:2][N:3]([C:10]([CH2:12][N:13]1[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])=[N:16][CH:15]([NH:31][C:42]([NH:41][C:37]3[CH:38]=[CH:39][CH:40]=[C:35]([C:34]([F:33])([F:54])[F:55])[CH:36]=3)=[O:43])[C:14]1=[O:32])=[O:11])[CH2:4]2

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 19081160(3RS)-1-{(3-azabicyclo[3.2.2]non-3-yl)-carbonylmethyl}-3-amino-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-oneHCID 19081325HCID 19081325, compound

Product 1

HCID 19081333N-[(3RS)-1-{(3-azabicyclo[3.2.2]non-3-yl)-carbonylmethyl}-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-trifluoromethylphenyl)ureaYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 7914Diisopropyl EtherSolvent

Procedure

To a solution of (3RS)-1-{(3-azabicyclo[3.2.2]non-3-yl)-carbonylmethyl}-3-amino-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (100mg) and 4-nitrophenyl N-(3-trifluoromethylphenyl)carbamate (90.1 mg) in dimethylformamide (2 ml) was added triethylamine (28 mg) under stirring at ambient temperature. The mixture was stirred for 3.5 hours under the same condition. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water three times and dried over magnesium sulfate. The solvent was removed in vacuo to give an amorphous mass, which was pulverized in diisopropyl ether under vigorous stirring. The resulting powder was collected by filtration and washed with diisopropyl ether to afford N-[(3RS)-1-{(3-azabicyclo[3.2.2]non-3-yl)-carbonylmethyl}-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-(3-trifluoromethylphenyl)urea (124.4 mg).

Workup

  1. stirringThe mixture was stirred for 3.5 hours under the same condition
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with water three times
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customto give an amorphous mass, which
  7. filtrationThe resulting powder was collected by filtration
  8. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-ad7066b9110c45a18738f72280e621f7
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Linked notes

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