Sodium hydride → ethyl 3-(1-methyl-1H-pyrazol-5-yl)-3-oxo-2-(thiophen-3-yl)propanoate

HRID 401199Notes

Reaction equation

[CH3:1][N:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=[N:3]1.C1N=CN(C(N2C=NC=C2)=O)C=1.[S:22]1[CH:26]=[CH:25][C:24]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:23]1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[CH3:1][N:2]1[C:6]([C:7](=[O:9])[CH:27]([C:24]2[CH:25]=[CH:26][S:22][CH:23]=2)[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:5][CH:4]=[N:3]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 1-methyl-1H-pyrazole-5-carboxylic acid (300 mg, 2.4 mmol) in DMF (7 mL) was added CDI (372 mg, 2.6 mmol), and the reaction mixture was heated to 50° C. for two hours. Then the mixture was cooled to −5° C., a solution of ethyl 2-(thiophen-3-yl)acetate (444 mg, 2.6 mmol) in DMF (1 mL) was added to the mixture and NaH (330 mg, 8.2 mmol) was added in portions. The mixture was stirred at 0° C. for 10 minutes, then warmed to room temperature and stirred for 1 hour. Ice water was added, followed by a standard aqueous/EtOAc workup. Crude was purified by column chromatography (PE: EtOAc=5:1) (150 mg, yield: 22.7%).

Workup

temperatureThen the mixture was cooled to −5° C.
additionwas added in portions
temperaturewarmed to room temperature
stirringstirred for 1 hour
customCrude was purified by column chromatography (PE: EtOAc=5:1) (150 mg, yield: 22.7%)

Sources & evidence

ORD record: ord-709524e136264d5d98337d94d23aebfe
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08741915B2

Reaction notes

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