Pyridine → 1-[1-(2-toluoylmethyl)-2-oxo-5-isobutyryl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

HRID 1979373Notes

Reaction equation

HRID 1979373 reaction equation
[C:1]1([CH3:38])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[NH:14][CH2:13][CH:12]([NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:27]=3)=[O:24])[C:11]2=[O:37])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:39](Cl)(=[O:43])[CH:40]([CH3:42])[CH3:41].N1C=CC=CC=1>ClCCCl>[C:1]1([CH3:38])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:39](=[O:43])[CH:40]([CH3:42])[CH3:41])[CH2:13][CH:12]([NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:27]=3)=[O:24])[C:11]2=[O:37])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 62325Isobutyryl chlorideHCID 212016301-[1-(2-toluoylmethyl)-2-oxo-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212019441-[1-(2-toluoylmethyl)-2-oxo-5-isobutyryl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)ureaYield 113.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-[1-(2-Toluoylmethyl)-2-oxo-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (500 mg) obtained from Step 1 of Example 93 was suspended in 1,2-dichloroethane (10 ml), isobutyryl chloride (114 mg) and pyridine (86 μl) were added thereto at room temperature, and the mixture was refluxed for 2 hours and 30 minutes. The reaction mixture was allowed to cool, washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=2:1), to thereby obtain 647 mg of the titled compound (Yield: 100%).

Workup

  1. temperatureto cool
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-86bbdfd48a6c4f91a27c0738ba54366f
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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