Hydrochloric Acid → 1-(4-cyanopyridin-2-yl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylic acid

HRID 514394Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)=[CH:12][C:11]([C:21]([O:23]C)=[O:22])=[N:10]2)[CH:4]=1)#[N:2].[OH-].[Na+].Cl>CN(C=O)C.C1COCC1.O>[C:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)=[CH:12][C:11]([C:21]([OH:23])=[O:22])=[N:10]2)[CH:4]=1)#[N:2]

Participants

Conditions

Temperature: 65 °C

Procedure

A solution of methyl 1-(4-cyanopyridin-2-yl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylate (500 mg, 1.57 mmol) in DMF/THF (1:1, 15 mL) was heated to 65° C. and NaOH (628 mg, 15.7 mmol) in water (1 mL) was added. The resulting solution was stirred at 65° C. and monitored by TLC. The reaction was cooled to rt at the point where a second more polar eluting product (relative to the product spot) began to form. The pH of the solution was adjusted to pH=4 with 6 N HCl, and the reaction mixture was extracted with EtOAc (2×50 mL). The organic layers were combined, washed with water (2×50 mL), dried (MgSO4), filtered, concentrated, and purified by flash column chromatography (EtOAc:hexanes=40:60) to give the title compound (196 mg, 41%).

Workup

temperatureThe reaction was cooled to rt at the point where a second more polar eluting product (relative to the product spot)
customto form
extractionthe reaction mixture was extracted with EtOAc (2×50 mL)
washwashed with water (2×50 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
custompurified by flash column chromatography (EtOAc:hexanes=40:60)

Sources & evidence

ORD record: ord-0b1464da48b04014a756b7d633f87527
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09107916B2

Reaction notes

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