Carbamic acid,n-[2-amino-5-(dimethylamino)-4-(trifluoromethyl)phenyl]-,1,1-dimethylethyl ester → 4-(3-Bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one

HRID 1265932Notes

Reaction equation

HRID 1265932 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:16])[CH3:15])[C:11]([C:17]([F:20])([F:19])[F:18])=[CH:10][C:9]=1[NH2:21])(C)(C)C.C(O[C:28](=[O:45])[CH2:29][C:30](=O)[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([O:42]C)(OC)[CH2:38][Br:39])[CH:32]=1)(C)(C)C>C1(C)C=CC=CC=1>[Br:39][CH2:38][C:37]([C:33]1[CH:32]=[C:31]([C:30]2[CH2:29][C:28](=[O:45])[NH:21][C:9]3[CH:10]=[C:11]([C:17]([F:18])([F:19])[F:20])[C:12]([N:14]([CH3:16])[CH3:15])=[CH:13][C:8]=3[N:7]=2)[CH:36]=[CH:35][CH:34]=1)=[O:42]

Participants

4

Reactant 2

HCID 67362752Carbamic acid,n-[2-amino-5-(dimethylamino)-4-(trifluoromethyl)phenyl]-,1,1-dimethylethyl esterHCID 696887173-Oxo-3-[3-(2-bromo-1,1-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester

Product 1

HCID 186131794-(3-Bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-oneYield 46.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (0.32 g) and 3-oxo-3-[3-(2-bromo-1,1-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester (0.43 g) (Example K28) in toluene (3 mL) was heated to 100° C. for 2 h. The solvent was evaporated in vacuum and the crude product was purified by chromatography on silica gel using AcOEt/Hexan(1:3) as eluent. A solution of the purified material (0.57 g) in CH2Cl2/TFA (1:1, 7 mL) was stirred at 20° C. for 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated to give crude 4-(3-bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one (0.22 g) as light-brown solid.

Workup

  1. customwas heated to 100° C. for 2 h
  2. customThe solvent was evaporated in vacuum
  3. customthe crude product was purified by chromatography on silica gel
  4. customevaporated
  5. dissolutionThe residual oil was dissolved in AcOEt
  6. washthe solution was washed with IN HCl and with brine
  7. customdried
  8. customevaporated

Sources & evidence

ORD record
ord-c9711f5810634ae1a209b2382ec6059d
Source dataset
uspto-grants-2003_04
Patent number
US06544985B2

Reaction notes

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