Methyl iodide → 3(R,S)-[(Benzyloxycarbonyl)amino]-5-cydohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 235241Notes

Reaction equation

HRID 235241 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[CH3:33]>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]([CH3:33])[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 6328Methyl iodideHCID 24758Sodium hydrideHCID 135413400Z-(R,S)-3-amino-5-cyclohexyl-2-oxo-1,4-benzodiazepine

Product 1

HCID 152352853(R,S)-[(Benzyloxycarbonyl)amino]-5-cydohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-oneYield 66.1%

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 (1.1 g, 2.8 mmol) in dimethylformamide (13 ml), under an atmosphere of nitrogen, was treated with sodium hydride (117 mg of a 55-60% dispersion in mineral oil, 2.8 mmol) in one portion, at -10° C. After 30 min at -10° C., iodomethane (174 μl, 2.8 mmol) was added in one portion and the solution allowed to reach 0° C. over 1 h. The solvent was then removed in vacuo and the crude residue partitioned between water (100 ml) and dichloromethane (100 ml). The organic phase was separated and the aqueous phase extracted with dichloromethane (2×100 ml). The combined organic layers were washed with brine, dried (MgSO4) and evaporated. The residue was chromatographed on silica, using 1:1 petrol:ethyl acetate as the eluant, to afford the title compound (0.75 g, 66%) as a white solid. mp 205-207° C. 1H NMR (360 MHz, CDCl3) δ1.03-2.04 (10H, m), 2.76 (1H, m), 3.36 (3H, s), 5.10 (3H, m), 6.52 (1H, d, J=8 Hz), 7.25-7.55 (9H, m).

Workup

  1. customat -10° C
  2. waitto reach 0° C. over 1 h
  3. customThe solvent was then removed in vacuo
  4. customthe crude residue partitioned between water (100 ml) and dichloromethane (100 ml)
  5. customThe organic phase was separated
  6. extractionthe aqueous phase extracted with dichloromethane (2×100 ml)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was chromatographed on silica

Sources & evidence

ORD record
ord-b023193bf2684e5291d1780b8c4a79f0
Source dataset
uspto-grants-1997_01
Patent number
US05597915

Reaction notes

Loading…