(2-Amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester → 4-(3-Bromoacetyl-phenyl)-8-chloro-7-dimethylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one

HRID 1265922Notes

Reaction equation

HRID 1265922 reaction equation
C(O[C:6](=[O:23])[CH2:7][C:8](=O)[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([O:20]C)(OC)[CH2:16][Br:17])[CH:10]=1)(C)(C)C.C(OC(=O)[NH:30][C:31]1[CH:36]=[C:35]([N:37]([CH3:39])[CH3:38])[C:34]([Cl:40])=[CH:33][C:32]=1[NH2:41])(C)(C)C>C1(C)C=CC=CC=1>[Br:17][CH2:16][C:15]([C:11]1[CH:10]=[C:9]([C:8]2[CH2:7][C:6](=[O:23])[NH:41][C:32]3[CH:33]=[C:34]([Cl:40])[C:35]([N:37]([CH3:38])[CH3:39])=[CH:36][C:31]=3[N:30]=2)[CH:14]=[CH:13][CH:12]=1)=[O:20]

Participants

4

Reactant 2

HCID 69688689(2-Amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl esterHCID 696887173-Oxo-3-[3-(2-bromo-1,1-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester

Product 1

HCID 186132344-(3-Bromoacetyl-phenyl)-8-chloro-7-dimethylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 3-oxo-3-[3-(2-bromo-1,1-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester (2.34 g) (Example K28) and (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J2) (1.57 g) in toluene (16 mL) was heated to 100° C. for 5 h. The solvent was evaporated in vacuum and the crude product was purified by chromatography on silica gel using CH2Cl2/AcOEt (1:20) as eluent. A solution of the purified material (2.4 g) in CH2Cl2/TFA (1:1, 30 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 1N HCl and with brine, dried and evaporated. The residue was crystallized from AcOEt/Et2O to give 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one as light-brown solid.

Workup

  1. customwas heated to 100° C. for 5 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 1N HCl and with brine
  7. customdried
  8. customevaporated
  9. customThe residue was crystallized from AcOEt/Et2O

Sources & evidence

ORD record
ord-53bcde81c4af47bca61a73ae0b099ed5
Source dataset
uspto-grants-2003_04
Patent number
US06544985B2

Reaction notes

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