Sodium hydride → N-{1-[(6-methyl-2-pyridinyl)methyl]-1H-pyrazol-3-yl}acetamide

HRID 522609Notes

Reaction equation

[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]1.[H-].[Na+].Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=1>C1COCC1>[CH3:13][C:14]1[N:15]=[C:16]([CH2:20][N:1]2[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]2)[CH:17]=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Intermediate 1 (97 mg, 0.774 mmol) was dissolved in 8 mL of THF (anh), at 0° C. NaH (ALDRICH, 31 mg, 0.774 mmol) was added, and mixture of reaction was stirred at 0° C. for 30 minutes. A solution of Intermediate 11 (144 mg, 0.774 mmol) in 2 mL THF (anh) was added to the mixture. Reaction was heated at 75° C. overnight. Mixture of reaction was partitioned between distilled water, EtOAc (×3) and DCM. Organic layers were dried over MgSO4 (anh) and filtered. Solvent was evaporated under vacuum. Residue was purified by silica chromatography column using a linear gradient of DCM/MeOH as eluents to give the title compound (133 mg, 0.578 mmol, 75% yield). 1H NMR (300 MHz, DMSO-d6) ppm: 10.40 (br s, 1H), 7.72 (d, 1H), 7.60-7.66 (m, 1H), 7.17-7.16 (m, 1H), 6.74-6.77 (m, 1H), 6.49 (d, 1H), 5.24 (s, 2H), 2.44 (s, 3H), 1.95 (s, 3H). [ES+MS] m/z 231 (MH+).

Workup

additionmixture of reaction
customReaction
temperaturewas heated at 75° C. overnight
additionMixture of reaction
customwas partitioned
distillationbetween distilled water, EtOAc (×3) and DCM
dry with materialOrganic layers were dried over MgSO4 (anh)
filtrationfiltered
customSolvent was evaporated under vacuum
customResidue was purified by silica chromatography column

Sources & evidence

ORD record: ord-dacca3c64840402392333b83763af68f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334265B2

Reaction notes

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