Dimethylformamide → (3RS)-1-[(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl]-3-benzyloxy-carbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one

HRID 1596336Notes

Reaction equation

HRID 1596336 reaction equation
[H-].[Na+].C(O[C:11]([NH:13][CH:14]1[N:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[C:18]2[CH:24]=[CH:25][CH:26]=[CH:27][C:17]=2[NH:16][C:15]1=[O:28])=[O:12])C1C=CC=CC=1.Br[CH2:30][C:31]([N:33]1[CH2:39][CH:38]2[CH2:40][CH2:41][CH:35]([CH2:36][CH2:37]2)[CH2:34]1)=[O:32].CN(C)[CH:44]=[O:45]>>[CH:35]12[CH2:41][CH2:40][CH:38]([CH2:37][CH2:36]1)[CH2:39][N:33]([C:31]([CH2:30][N:16]1[C:17]3[CH:27]=[CH:26][CH:25]=[CH:24][C:18]=3[C:19]([CH:21]([CH3:22])[CH3:23])=[N:20][C:14]([N:13]=[C:11]=[O:12])([O:45][CH2:44][C:17]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:18]=3)[C:15]1=[O:28])=[O:32])[CH2:34]2

Participants

5

Reactant 4

HCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 21701395N-bromomethylcarbonyl-3-azabicyclo[3.2.2]nonaneHCID 135813678(3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one

Product 1

HCID 86584132(3RS)-1-[(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl]-3-benzyloxy-carbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one

Procedure

To a suspension of sodium hydride (0.123 g of a 65% dispersion in mineral oil) in dry N, N-dimethylformamide (10 ml) was added dropwise a solution of (3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one (1.00 g) in dry N,N-dimethylformamide (5 ml) under cooling in an ice-bath. The mixture was stirred at the same temperature for 1 hour and then at room temperature for 1 hour. To the mixture was added dropwise a solution of N-bromomethylcarbonyl-3-azabicyclo[3.2.2]nonane (0.77 g) in dry N,N-dimethylformamide (5 ml) and stirred at the same condition for 2 hours. The reaction mixture was concentrated in vacuo and the residue was taken up with ethyl acetate (100 ml) and a saturated aqueous sodium hydrogen carbonate (100 ml). The organic layer was washed with a brine (50 ml) and dried over anhydrous magnesium sulfate. Filtration and evaporation gave (3RS)-1-[(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl]-3-benzyloxy-carbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one.

Workup

  1. temperatureunder cooling in an ice-bath
  2. waitat room temperature for 1 hour
  3. stirringstirred at the same condition for 2 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. washThe organic layer was washed with a brine (50 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationFiltration and evaporation

Sources & evidence

ORD record
ord-3d67565a78134bd0a5b2e880c167862b
Source dataset
uspto-grants-2001_09
Patent number
US06291452B1

Reaction notes

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