2-bromo-N-isopropyl-N-phenyl-acetamide → 2-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide

HRID 900129

Reaction equation

HRID 900129 reaction equation
[CH2:1]([O:3][C:4]1[CH2:10][C:9](=[O:11])[NH:8][C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:6]=2[N:5]=1)[CH3:2].Br[CH2:17][C:18]([N:20]([CH:27]([CH3:29])[CH3:28])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:19]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[CH2:10][C:9](=[O:11])[N:8]([CH2:17][C:18]([N:20]([CH:27]([CH3:29])[CH3:28])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:19])[C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:6]=2[N:5]=1)[CH3:2]

Participants

5

Reactant 2

HCID 152160012-bromo-N-isopropyl-N-phenyl-acetamide2×HCID 589579152H-1,5-Benzodiazepin-2-one, 4-ethoxy-1,3-dihydro-

Product 1

HCID 589579362-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-17 °C

Procedure

To a solution of 4-ethoxy-1,3-dihydro-benzo[b][1,4]diazepin-2-one (Preparation 3(A) (5.0 g, 24.5 mmol) in DMF (100 mL) was added potassium bistrimethyl silyl amide (49 mL of 0.5 M solution in toluene, 24.5 mmol) at 0° C. The reaction mixture was stirred for 20 minutes and was cooled to −17° C. A solution of 2-bromo-N-isopropyl-N-phenyl-acetamide (Preparation 1(A) (6.9 g, 27 mmol) in DMF (50 mL) was added dropwise so the internal temperature remained below −15° C. The reaction mixture was stirred at −16° C. for 1 hour, was warmed to room temperature and was diluted with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate and was concentrated. The resulting pale brown solid was triturated with ether to obtain 3.2 g of 2-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide as a white powder. The filtrate was concentrated and the residue was triturated with ether/hexanes. The solid was collected by filtration to give a second crop of 2-(4-ethoxy-2-oxo-2,3-dihydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide (3.4 g). MS 380.2 (M+1).

Workup

  1. additionwas added dropwise so the internal temperature
  2. customremained below −15° C
  3. stirringThe reaction mixture was stirred at −16° C. for 1 hour
  4. temperaturewas warmed to room temperature
  5. washThe organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationwas concentrated
  8. customThe resulting pale brown solid was triturated with ether

Sources & evidence

ORD record
ord-c0b8b50a831043d0a9159dcbb92003ed
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Linked notes

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