Acetic Acid → HCID 178475837, compound

HRID 1012065Notes

Reaction equation

[NH2:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:10][C:11]([C:13]1[C:17]([NH:18][C:19](=[O:28])[C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])=[CH:16][NH:15][N:14]=1)=O.[C:29]([OH:32])(=[O:31])[CH3:30]>>[F:27][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]([F:26])[C:20]=1[C:19]([NH:18][C:17]1[C:13]([C:11]2[NH:10][C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([CH2:8][OH:9])[C:2]=3[N:1]=2)=[N:14][NH:15][CH:16]=1)=[O:28].[F:27][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]([F:26])[C:20]=1[C:19]([NH:18][C:17]1[C:13]([C:11]2[NH:10][C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([CH2:8][O:31][C:29](=[O:32])[CH3:30])[C:2]=3[N:1]=2)=[N:14][NH:15][CH:16]=1)=[O:28]

Participants

Reactant 2

HCID 176Acetic Acid

HCID 178507937HCID 178507937, compound

Product 2

HCID 178475837HCID 178475837, compound

HCID 178522442HCID 178522442, compound

Conditions

Temperature: 150 °C

Procedure

4-(2,6-Difluoro-benzoylamino)-1H-pyrazole-3-carboxylic acid (2-amino-3-hydroxymethyl-phenyl)-amide (100 mg, 0.26 mmol) was dissolved in acetic acid (10 ml) then heated for 10 min at 150° C. (100 W) in a CEM discover microwave synthesiser. The reaction mixture was reduced then azeotroped with toluene (2×20 ml). The residue was purified by flash column chromatography [SiO2, EtOAc-hexane (1:1, 2:1, 3:1)] to give 2,6-difluoro-N-[3-(4-hydroxymethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-benzamide (25 mg) as an off white solid (LC/MS: Rt 2.70, [M+H]+ 370) and acetic acid 2-[4-(2,6-difluoro-benzoylamino)-1H-pyrazol-3-yl]-1H-benzimidazol-4-ylmethyl ester (20 mg) as an off white solid. (LC/MS: Rt 3.60, [M+H]+ 412).

Workup

customThe reaction mixture was reduced then azeotroped with toluene (2×20 ml)
customThe residue was purified by flash column chromatography [SiO2, EtOAc-hexane (1:1, 2:1, 3:1)]

Sources & evidence

ORD record: ord-cf3c45538fd14d579f36ccaa249d1b22
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977477B2

Reaction notes

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