Isobutyl iodide → 1,3-dihydro-1-(2-methylpropyl)-5-(2-propyl)-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one

HRID 2399682Notes

Reaction equation

HRID 2399682 reaction equation
[CH3:1][CH:2]([C:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[NH:8][C:7](=[O:15])[CH:6]([NH:16][C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[N:5]=1)[CH3:3].[H-].[Na+].[CH3:29][CH:30]([CH3:33])[CH2:31]I>CN(C)C=O>[CH3:29][CH:30]([CH3:33])[CH2:31][N:8]1[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:4]([CH:2]([CH3:1])[CH3:3])=[N:5][CH:6]([NH:16][C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:7]1=[O:15]

Participants

5

Reactant 3

HCID 10556Isobutyl iodideHCID 24758Sodium hydrideHCID 135813678(3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one

Product 1

HCID 764123211,3-dihydro-1-(2-methylpropyl)-5-(2-propyl)-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-oneYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1,3-dihydro-5-(2-propyl)-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one (500 mg, 1.42 mmol) in dimethylformamide (10 ml) under an atmosphere of nitrogen, was treated with sodium hydride (57 mg of a 57% dispersion in mineral oil, 1.42 mmol) in one portion at 0° C. After 1 h, 2-methylpropyl iodide (0.17 ml, 1.50 mmol) was added and the resulting mixture was stirred at room temperature for 16 h. The solvent was then evaporated and the crude residue partitioned between water (15 ml) and dichloromethane (2×20 ml). The combined organic phase was washed with brine (20 ml), dried (MgSO4) and evaporated. The residue was chromatographed on silica using 1:3 ethyl acetate:petrol as eluent, to afford 1,3-dihydro-1-(2-methylpropyl)-5-(2-propyl) -3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one (530 mg, 92%) as a colourless solid. 1H NMR (250 MHz, CDCl3) δ 0.72 (3H, d, J=8 Hz), 0.80 (3H, d, J =8 Hz), 1.02 (3H, d, J=7 Hz), 1.30 (3H, d, J=7 Hz), 1.64 (1H, m), 3.10 (1H, m), 3.42 (1H, dd, J=15 Hz, 5 Hz), 4.30 (1H, dd, J=12.5 Hz, J=7.5 Hz), 5.12 (3H, m), 6.55 (1H, d, J=10 Hz), 7.10-7.70 (9H, m).

Workup

  1. customThe solvent was then evaporated
  2. customthe crude residue partitioned between water (15 ml) and dichloromethane (2×20 ml)
  3. washThe combined organic phase was washed with brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was chromatographed on silica using 1:3 ethyl acetate

Sources & evidence

ORD record
ord-a604f8a258144932bf5c320995fe903a
Source dataset
uspto-grants-1995_09
Patent number
US05451582

Reaction notes

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