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

HRID 1979364Notes

Reaction equation

HRID 1979364 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.[Cl:39][CH2:40][C:41]([CH3:46])([CH3:45])[C:42](Cl)=[O:43].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:42](=[O:43])[C:41]([CH3:46])([CH3:45])[CH2:40][Cl:39])[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 613453-Chloro-2,2-dimethylpropanoyl 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 212015641-[1-(2-toluoylmethyl)-2-oxo-5-(3-chloro-2,2-dimethylpropionyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)ureaYield 82.7%

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), chloropivaloyl chloride (166 mg) and pyridine (86 μl) were added, and the mixture was refluxed for 2 hours 30 minutes. The reaction mixture was successively washed with water,1N hydrochloric acid, and saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate. 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 509 mg of the titled compound (Yield: 81%).

Workup

  1. temperaturethe mixture was refluxed for 2 hours 30 minutes
  2. washThe reaction mixture was successively washed with water,1N hydrochloric acid, and 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-c4ed2293c4334ce9affd81110d2bb2b0
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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