Methanol → 7-Difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

HRID 418160Notes

Reaction equation

[NH2:1][C:2]1[C:6]([C:7]([O:9]CC)=[O:8])=[CH:5][NH:4][N:3]=1.[F:12][CH:13]([F:29])[C:14](=O)[CH2:15][C:16]([C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)=O.CO.S(=O)(=O)(O)O>C(O)(=O)C.[OH-].[K+].O>[F:29][CH:13]([F:12])[C:14]1[N:3]2[N:4]=[CH:5][C:6]([C:7]([OH:9])=[O:8])=[C:2]2[N:1]=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:25])([F:26])[F:27])=[CH:20][CH:19]=2)[CH:15]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A stirred mixture of commercially available 3-amino-4-ethoxycarbonyl-pyrazole (3.38 g, 22 mmol) and 4,4-difluoro-1-(4-trifluoromethyl-phenyl)-butane-1,3-dione (5.8 g, 22 mmol) in acetic acid (45 ml) was heated under reflux conditions for 1.5 h. The reaction mixture was evaporated and the crude product (yellow solid, 8.5 g, 22 mmol) was dissolved in a mixture of 2M KOH in methanol (176.5 ml, 0.35 mol) and water (85 ml). The reaction mixture was stirred at 60° C. for 1.5 h, poured into ice/water (200 ml), acidified with 3N sulfuric acid (pH=4) and stirred at room temperature for 30 min. The precipitate was collected by filtration and further purified by crystallization from diethylether/methanol to give the title compound (4.51 g, 57%) as an off-white solid. MS (ISP) 356.1 [(M−H)−]; m.p. 261° C.

Workup

temperaturewas heated under reflux conditions for 1.5 h
customThe reaction mixture was evaporated
stirringstirred at room temperature for 30 min
filtrationThe precipitate was collected by filtration
customfurther purified by crystallization from diethylether/methanol

Sources & evidence

ORD record: ord-0bbff0786f9a4612ab00286e213b5624
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093263B2

Reaction notes

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