Water → 2-Fluoro-6-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-nicotinic acid methyl ester

HRID 1952121Notes

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].[F:13][C:14]([F:24])([F:23])[C:15]1[N:20]=[CH:19][C:18]([CH2:21][NH2:22])=[CH:17][CH:16]=1.O>CN(C)C=O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([NH:22][CH2:21][C:18]2[CH:19]=[N:20][C:15]([C:14]([F:24])([F:13])[F:23])=[CH:16][CH:17]=2)=[N:6][C:5]=1[F:11]

Participants

Conditions

Temperature: -40 °C

Procedure

To 2,6-difluoro-nicotinic acid methyl ester (60, 1.82 g, 0.0105 mol, prepared as described in Example 22, Scheme 24, Step 2) in N,N-dimethylformamide (20.0 mL), under an atmosphere of nitrogen at −40° C., C-(6-trifluoromethyl-pyridin-3-yl)-methylamine (561, 1.00 g, 5.68 mmol) was added. The reaction was stirred at −40° C., then allowed to warm to room temperature for 2 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 35% to 100% ethyl acetate in hexane to give a white solid (562, 1.40 g, 74.9). MS (ESI) [M+H+]+=330.1.

Workup

temperatureto warm to room temperature for 2 hours
extractionextracted with ethyl acetate
dry with materialThe organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationThe filtrate was concentrated
custompurified by silica gel column chromatography
washeluting with 35% to 100% ethyl acetate in hexane
customto give a white solid (562, 1.40 g, 74.9)

Sources & evidence

ORD record: ord-2c608ca8b4154dd2a8ff330846b6fd26
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404700B2

Reaction notes

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