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

HRID 743691Notes

Reaction equation

HRID 743691 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[N:18]=[C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=2[NH:14][C:13]1=[O:29])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH2:33][CH2:34][CH3:35]>CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][CH:12]1[N:18]=[C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]=2[N:14]([CH2:33][CH2:34][CH3:35])[C:13]1=[O:29])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3(R,S)-[(benzyloxycarbonyl)amino]-5-cyclohexyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (Example 2, Step 3, 2 g) 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 (0.55 ml) was added in one portion and the solution allowed to reach ambient temperature and stirred overnight. 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). 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. customSolvent 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-0f8d2e9767bf4bc1990f0712e29d1db0
Source dataset
uspto-grants-1996_09
Patent number
US05556969

Reaction notes

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