Dimethylformamide → 1-Methyl-4-trifluoromethyl-1h-pyrrole-3-carboxylic acid[2-(2-cyclopropylcyclobutyl)phenyl]amide

HRID 2240481Notes

Reaction equation

HRID 2240481 reaction equation
CN1C=C[C:4]([C:7]([OH:9])=O)=[C:3]1[C:10]([F:13])([F:12])[F:11].[CH3:14][N:15]([CH:17]=O)[CH3:16].[CH:19]1([CH:22]2[CH2:25][CH2:24][CH:23]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[NH2:32])[CH2:21][CH2:20]1.C(N(CC)CC)C>C(Cl)Cl>[CH:19]1([CH:22]2[CH2:25][CH2:24][CH:23]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[NH:32][C:7]([C:4]2[C:3]([C:10]([F:11])([F:12])[F:13])=[CH:16][N:15]([CH3:14])[CH:17]=2)=[O:9])[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 110087751-methyl-2-(trifluoromethyl)-1H-pyrrole-3-carboxylic acidHCID 685830202-(2-Cyclopropylcyclobutyl)phenylamine

Product 1

HCID 685856801-Methyl-4-trifluoromethyl-1h-pyrrole-3-carboxylic acid[2-(2-cyclopropylcyclobutyl)phenyl]amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

190 mg (1 mmol) 1-Methyl-trifluoromethyl-1H-pyrrole-3-carboxylic acid and 140 mg (1.05 mmol) oxalylic acid chloride were dissolved in 10 ml methylene chloride. The solution was stirred for 3 hours at room temperature in the presence of catalytic amounts of DMF. Then the resulting reaction mixture was slowly added to a solution consisting of 190 mg (1 mmol) 2-(2-cyclopropylcyclobutyl)phenylamine (prepared as described in Example 5), 200 mg (2 mmol) of triethylamine and 10 ml methylene chloride. After stirring for 16 hours at room temperature the solvent was distilled off and the raw material purified by flash chromatography over silica gel (eluant: hexane/methylene chloride/ethyl acetate 2:2:1). Yield: 240 mg (66% of theory) of 1-methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid [2-(2-cyclopropylcyclobutyl)phenyl]amide (cis-isomer) in the form of slightly yellow crystals (mp.: 167-169° C.).

Workup

  1. customThen the resulting reaction mixture
  2. additionwas slowly added to a solution
  3. distillationwas distilled off
  4. customthe raw material purified by flash chromatography over silica gel (eluant: hexane/methylene chloride/ethyl acetate 2:2:1)

Sources & evidence

ORD record
ord-16f2e4416b104defa6052f6a8095d245
Source dataset
uspto-grants-2010_05
Patent number
US07723371B2

Reaction notes

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