3-(Trifluoromethyl)benzoyl chloride → N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)-4-methylphenyl]-3-(trifluoromethyl)benzamide

HRID 1874590

Reaction equation

HRID 1874590 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:21]([CH3:24])=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[CH:11]=1.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30](Cl)=[O:31]>CN1CCCC1=O>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:3]=[C:2]([NH:1][C:30](=[O:31])[C:29]5[CH:33]=[CH:34][CH:35]=[C:27]([C:26]([F:25])([F:36])[F:37])[CH:28]=5)[CH:23]=[CH:22][C:21]=4[CH3:24])=[CH:11][N:10]3[N:12]=2)=[O:17])[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 57749340N-[6-(3-amino-6-methylphenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57749304N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)-4-methylphenyl]-3-(trifluoromethyl)benzamideYield 65.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of N-[6-(3-amino-6-methylphenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (100 mg, 0.309 mmol) in 1-methylpyrrolidin-2-one (2.0 mL) was added 3-(trifluoromethyl)benzoyl chloride (78 mg, 0.371 mmol), and the mixture was stirred at room temperature for 10 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate (100 mL), washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), and dried over anhydrous sodium sulfate. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=50/50→0/100), and the obtained oil was triturated with ethyl acetate and hexane to give the title compound (100 mg, 65%) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate (100 mL)
  3. washwashed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe insoluble material was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=50/50→0/100)
  8. customthe obtained oil was triturated with ethyl acetate and hexane

Sources & evidence

ORD record
ord-879d9d555fa54336bc729854755a3c29
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

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