Sodium hydride → 3(R,S)-[(Benzyloxycarbonyl)amino]-5-cyclohexyl-1,3-dihydro-1-propyl-2H-1,4-benzodiazepin-2-one

HRID 2379341Notes

Reaction equation

HRID 2379341 reaction equation
[CH:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[O:18])[CH:9]([NH:19][C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].I[CH2:33][CH2:34][CH3:35]>CN(C)C=O>[CH:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH2:33][CH2:34][CH3:35])[C:10](=[O:18])[CH:9]([NH:19][C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 336431-IodopropaneHCID 135413400Z-(R,S)-3-amino-5-cyclohexyl-2-oxo-1,4-benzodiazepine

Product 1

HCID 214804833(R,S)-[(Benzyloxycarbonyl)amino]-5-cyclohexyl-1,3-dihydro-1-propyl-2H-1,4-benzodiazepin-2-oneYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-cyclohexyl-1,3-dihydro-3(R,S)-[(benzyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one ( 2 g, 5.1 mmol) in anhydrous dimethylformamide (15 ml), under an atmosphere of nitrogen, was treated with sodium hydride (0.22 g of a 55-60% dispersion in mineral oil, 5.1 mmol) in one portion, at 0° C. After 45 min at 0° C., 1-iodopropane (0.55ml, 5.6 mmol) was added in one portion and the solution allowed to reach ambient temperature and stirred overnight. After this time the solvent was removed under reduced pressure, and the crude residue partitioned between water (25 ml) and dichloromethane (25 ml). The organic phase was separated and the aqueous phase extracted with dichloromethane (3×25 ml). The combined organic layers were washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo. The residue was triturated with diethyl ether to give the title compound (1.74 g, 79%) as a colourless solid. mp 160°-163° C. 1H NMR (360 MHz, CDCl3) δ 0.82 (3H, t, J=10.5 Hz), 0.94-1.48 (5H, m), 1.50-1.76 (5H, m), 1.79-1.90 (1H, m), 1.96-2.08 (1H, m), 2,70-2.84 (1H, m), 3.46-3.59 (1H, m), 4.22-4.35 (1H, m), 5.06-5.16 (3H, m), 5.07 (1H, d, J=12.0 Hz), 7.21-7.40 (7H, m), 7.44-7.59 (2H, m).

Workup

  1. customat 0° C
  2. customto reach ambient temperature
  3. customAfter this time the solvent was removed under reduced pressure
  4. customthe crude residue partitioned between water (25 ml) and dichloromethane (25 ml)
  5. customThe organic phase was separated
  6. extractionthe aqueous phase extracted with dichloromethane (3×25 ml)
  7. washThe combined organic layers were washed with brine (50 ml)
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-b29ad4e0c1ed4c589375c8e54c61ecf9
Source dataset
uspto-grants-1994_11
Patent number
US05360802

Reaction notes

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