Anisole → HCID 178522425, compound

HRID 1012138Notes

Reaction equation

COC1C=CC(C[N:8]2[CH:12]=[C:11]([NH:13][C:14](=[O:26])[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21][C:22]([F:25])([F:24])[F:23])[C:10]([C:27]3[NH:31][C:30]4[CH:32]=[CH:33][C:34]([CH2:36][N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)=[CH:35][C:29]=4[N:28]=3)=[N:9]2)=CC=1.C1(OC)C=CC=CC=1>FC(F)(F)C(O)=O>[N:37]1([CH2:36][C:34]2[CH:33]=[CH:32][C:30]3[NH:31][C:27]([C:10]4[C:11]([NH:13][C:14](=[O:26])[C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=5[O:21][C:22]([F:23])([F:24])[F:25])=[CH:12][NH:8][N:9]=4)=[N:28][C:29]=3[CH:35]=2)[CH2:38][CH2:39][O:40][CH2:41][CH2:42]1

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of N-[1-(4-methoxy-benzyl)-3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-2-trifluoromethoxy-benzamide (50 mg) and anisole (25 μl) in trifluoroacetic acid (1 ml) was heated at 140° C. (100 W) for 20 min in a CEM Discover™ microwave synthesiser. The reaction mixture was evaporated and then azeotroped with toluene (2×10 ml). To the crude material was added EtOAc (5 ml) and the mixture neutralised with saturated aqueous sodium hydrogen carbonate. The organic portion was washed with water, dried (MgSO4) and reduced in vacuo. The residue was purified by flash column chromatography [SiO2, CH2Cl2-MeOH (100:0-95:5)] to give N-[3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-2-trifluoromethoxy-benzamide (12 mg) as a white solid. (LC/MS: Rt 2.06, [M+H]+ 487).

Workup

customThe reaction mixture was evaporated
customazeotroped with toluene (2×10 ml)
additionTo the crude material was added EtOAc (5 ml)
washThe organic portion was washed with water
dry with materialdried (MgSO4)
customThe residue was purified by flash column chromatography [SiO2, CH2Cl2-MeOH (100:0-95:5)]

Sources & evidence

ORD record: ord-a78a4848239244c883428a6e0082d226
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977477B2

Reaction notes

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