Sodium hydride → 3,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1865306Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:12])=[N:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2].[H-].[Na+].[H][H].Cl[C:18]1[CH:23]=[N:22][CH:21]=[CH:20][N:19]=1>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:12])=[N:8][N:9]([C:18]2[CH:23]=[N:22][CH:21]=[CH:20][N:19]=2)[C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

step 1—To a solution of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid ethyl ester (1 g, 5.95 mmol) in DMF (20 mL) cooled to 0° C. was added portionwise NaH (60% in mineral oil, 171 mg, 7.13 mmol). After hydrogen evolution ceased, 2-chloro-pyrazine (0.64 mL, 7.13 mmol) was added and the reaction was stirred at 50° C. for 24 h. The reaction mixture was cooled to RT, partitioned between EtOAc and saturated NH4Cl. The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried (Na2SO4), filtered and evaporated. The residue was purified via SiO2 chromatography eluting with hexane/EtOAc to afford 0.64 g (44%) of 3,5-dimethyl-1-pyrazin-2-yl-1H-pyrazole-4-carboxylic acid ethyl ester (124a). The ethyl ester was hydrolyzed to the corresponding acid with KOH in aqueous EtOH as described in step 2 of example 31.

Workup

temperatureThe reaction mixture was cooled to RT
custompartitioned between EtOAc and saturated NH4Cl
extractionThe aqueous layer was extracted twice with EtOAc
dry with materialThe combined organic layers were dried (Na2SO4)
filtrationfiltered
customevaporated
customThe residue was purified via SiO2 chromatography
washeluting with hexane/EtOAc

Sources & evidence

ORD record: ord-268eb24ec63f4dcf860b80cc557966a6
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07625905B2

Reaction notes

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