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

HRID 1784549Notes

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-b91f482d46e44f348a4614e2bcd0e8b7
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07504404B2

Reaction notes

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