Methanol → N-[3-({2-[(cyclopropylcarbonyl)amino]-1H-benzimidazol-6-yl}oxy)phenyl]-3-(trifluoromethyl)benzamide

HRID 2190501Notes

Reaction equation

HRID 2190501 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:13]=[C:12]([NH:14][C:15]([CH:17]3[CH2:19][CH2:18]3)=[O:16])[NH:11][C:10]=2[CH:20]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29](O)=[O:30].Cl.C(N=C=NCCCN(C)C)C.CO>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH:17]1([C:15]([NH:14][C:12]2[NH:11][C:10]3[CH:20]=[C:6]([O:5][C:4]4[CH:3]=[C:2]([NH:1][C:29](=[O:30])[C:28]5[CH:32]=[CH:33][CH:34]=[C:26]([C:25]([F:24])([F:35])[F:36])[CH:27]=5)[CH:23]=[CH:22][CH:21]=4)[CH:7]=[CH:8][C:9]=3[N:13]=2)=[O:16])[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 887MethanolHCID 99633-(Trifluoromethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57388051HCID 57388051, compound

Product 1

HCID 58349045N-[3-({2-[(cyclopropylcarbonyl)amino]-1H-benzimidazol-6-yl}oxy)phenyl]-3-(trifluoromethyl)benzamideYield 54.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To a solution of N-[6-(3-aminophenoxy)-1H-benzimidazol-2-yl]cyclopropanecarboxamide (159 mg, 516 μmol) and 3-(trifluoromethyl)benzoic acid (191 mg, 1.01 mmol) in pyridine (5 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (375 mg, 1.96 mmol) and N,N-dimethylpyridine-4-amine (18.5 mg, 151 μmol), and the mixture was stirred at room temperature for 12 hr. Methanol (5 mL) was added to the reaction mixture, and the mixture was further stirred at room temperature for 2 hr and concentrated under reduced pressure. The residue was diluted with methanol (1 mL) and ethyl acetate (30 mL), washed with 0.1N hydrochloric acid (50 mL) and saturated aqueous sodium hydrogencarbonate solution (50 mL), successively, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography (ethyl acetate/hexane=2/98→80/20), and the obtained crude crystals were recrystallized from acetone and diisopropyl ether to give the title compound (135 mg, 54%) as colorless crystals.

Workup

  1. stirringthe mixture was further stirred at room temperature for 2 hr
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with methanol (1 mL) and ethyl acetate (30 mL)
  4. washwashed with 0.1N hydrochloric acid (50 mL) and saturated aqueous sodium hydrogencarbonate solution (50 mL)
  5. dry with materialsuccessively, and dried over anhydrous magnesium sulfate
  6. filtrationThe insoluble material was filtered off
  7. concentrationthe filtrate was concentrated
  8. customthe obtained crude crystals
  9. customwere recrystallized from acetone and diisopropyl ether

Sources & evidence

ORD record
ord-4a5668aaa1994d3e9faa62f0f08764a1
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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