1-Hydroxybenzotriazole hydrate → 1-[4-Chloro-2-(trifluoromethyl)phenyl]-5-[2-(dimethylamino)-2-oxoethyl]-2-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide

HRID 238962

Reaction equation

HRID 238962 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[C:11]([C:14](=[O:26])[NH:15][C:16]3[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=3)[CH:10]=[C:9]2[CH2:27][C:28](O)=[O:29])=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=1.O.ON1C2C=CC=CC=2N=N1.[CH3:46][NH:47][CH3:48].C1COCC1>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9]([CH2:27][C:28]([N:47]([CH3:48])[CH3:46])=[O:29])=[CH:10][C:11]([C:14]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=3)=[O:26])=[C:12]2[CH3:13])=[C:4]([C:31]([F:33])([F:32])[F:34])[CH:3]=1

Participants

6

Reactant 3

HCID 27960291-Hydroxybenzotriazole hydrateHCID 22320367Dimethylamine tetrahydrofuranHCID 67376656(1-[4-chloro-2-(trifluoromethyl)phenyl]-5-methyl-4-{[4-(methylsulfonyl)phenyl]carbamoyl}-1H-pyrrol-2-yl)acetic acid

Product 1

HCID 452791841-[4-Chloro-2-(trifluoromethyl)phenyl]-5-[2-(dimethylamino)-2-oxoethyl]-2-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamideYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the above (1-[4-chloro-2-(trifluoromethyl)phenyl]-5-methyl-4-{[4-(methylsulfonyl)phenyl]carbamoyl}-1H-pyrrol-2-yl)acetic acid (30 mg, 0.518 mmol) in DMF (0.58 mL), 1-hydroxybenzotriazole monohydrate (18 mg, 0.12 mmol) and hydrochloric acid 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide (23 mg, 0.12 mmol) were successively added, and the mixture was stirred at room temperature for 1 hour. Thereafter, a 2M dimethylamine/THF solution was added to the mixture, and the mixture was stirred overnight. After the reaction, it was diluted with ethyl acetate, and the organic layer was washed with 1M hydrochloric acid, water and saturated brine. Thereafter, it was dried with sodium sulfate, filtration was carried out, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (17 mg, 54%).

Workup

  1. stirringthe mixture was stirred overnight
  2. customAfter the reaction, it
  3. washthe organic layer was washed with 1M hydrochloric acid, water and saturated brine
  4. dry with materialThereafter, it was dried with sodium sulfate, filtration
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-32ca8c75f39c49a292aee21de54de583
Source dataset
uspto-grants-2014_02
Patent number
US08642640B2

Linked notes

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