Dimethylformamide → 2-Fluoro-6-(6-methoxy-pyridin-3-ylamino)-nicotinic acid methyl ester

HRID 1396154Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](F)=[N:6][C:5]=1[F:11].CN(C)C=O.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=1.C(N(CC)CC)C>O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([NH:18][C:19]2[CH:24]=[N:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[N:6][C:5]=1[F:11]

Participants

Conditions

Temperature: -40 °C

Procedure

To a round bottom flask, 2,6-difluoro-nicotinic acid methyl ester (52, 2.00 g, 11.6 mmol) is combined with 20.0 mL of N,N-dimethylformamide under an atmosphere of nitrogen at −40° C. To this, 5-amino-2-methoxypyridine (53, 1.55 g, 12.5 mmol) and triethylamine (5.0 mL, 36.0 mmol) are added and the reaction stirred at −40° C., then warmed to room temperature and reacted overnight. The reaction is then heated to 50° C. over the weekend, then at 70° C. for 3 hours. The reaction is poured into water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (54, 1.20 g).

Workup

temperaturewarmed to room temperature
customreacted overnight
temperatureThe reaction is then heated to 50° C. over the weekend
extractionextracted with ethyl acetate
dry with materialThe organic layer is dried over sodium sulfate
filtrationfiltered
concentrationthe filtrate concentrated under vacuum
customThe resulting material is purified by silica gel column chromatography
washeluting with 20-100% ethyl acetate in hexane
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-8fbf9990cf274dd29d9eecc7f43b7d53
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901118B2

Reaction notes

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