Dimethylformamide → 4-(4-bromo-2,3-difluorophenyl)-N,2-dimethylnicotinamide

HRID 1398373Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14](O)=[O:15])=[C:12]([CH3:17])[N:11]=[CH:10][CH:9]=2)=[C:4]([F:18])[C:3]=1[F:19].C(Cl)(=O)C(Cl)=O.[CH3:26][N:27](C=O)C.Cl.CN.C(N(CC)CC)C>ClCCl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([NH:27][CH3:26])=[O:15])=[C:12]([CH3:17])[N:11]=[CH:10][CH:9]=2)=[C:4]([F:18])[C:3]=1[F:19]

Participants

Conditions

Temperature: 45 °C

Procedure

To a solution of 4-(4-bromo-2,3-difluorophenyl)-2-methylnicotinic acid (700 mg, 2.13 mmol) in dichloromethane (20 mL) at 0° C. was added oxalyl chloride (0.56 mL, 6.40 mmol) drop wise followed by DMF (0.03 mL, 0.43 mmol). The reaction mixture was heated to 45° C. for 4 h. The reaction mixture was evaporated to dryness. The residue was taken in dichloromethane (50 mL) at 0° C. and methylamine hydrochloride (1.56 g, 23.08 mmol) was added to it followed by triethylamine (4.83 mL, 34.6 mmol). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (100 mL). The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure to afford 4-(4-bromo-2,3-difluorophenyl)-N,2-dimethylnicotinamide (600 mg, 1.76 mmol, 76% crude yield) as yellow semi-solid which was carried on without further purification. LC/MS (ESI) m/e 343.0 [(M+2H)+, calcd for C14H13BrF2N2O 343.0]; LC/MS retention time (method C): tR=1.61 min.

Workup

customThe reaction mixture was evaporated to dryness
customwas taken in dichloromethane (50 mL) at 0° C.
extractionextracted with dichloromethane (100 mL)
customThe organic layer was separated
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-54d39c0c0a25411ea1aca55ef58a3424
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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