Diisopropylethylamine → 2-fluoro-N-(2-methoxy-4-pyridyl)-4,6-bis(trifluoromethyl)benzamide

HRID 1053168Notes

Reaction equation

HRID 1053168 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([NH2:9])[CH:6]=[CH:5][N:4]=1.CCN(C(C)C)C(C)C.[F:19][C:20]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[C:21]=1[C:22](Cl)=[O:23]>CN(C=O)C.C(OCC)(=O)C>[F:19][C:20]1[CH:28]=[C:27]([C:29]([F:31])([F:32])[F:30])[CH:26]=[C:25]([C:33]([F:34])([F:35])[F:36])[C:21]=1[C:22]([NH:9][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=1)=[O:23]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2808912-Methoxypyridin-4-amineHCID 467375822-Fluoro-4,6-bis(trifluoromethyl)benzoyl chloride

Product 1

HCID 867284822-fluoro-N-(2-methoxy-4-pyridyl)-4,6-bis(trifluoromethyl)benzamideYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-Methoxypyridin-4-amine (632.1 mg, 5.09 mmol) and DIEA (1.8 mL, 10.18 mmol) were dissolved in DMF (15 mL) and treated dropwise with a solution of 2-fluoro-4,6-bis(trifluoromethyl)benzoyl chloride (1500 mg, 5.09 mmol) in DMF (2 mL). After 2 hours, the reaction was diluted with ethyl acetate, washed with 50% saturated sodium bicarbonate solution (2×20 mL), water, and brine. The solution was dried over anhydrous Na2SO4, filtered, and dried down to a purple residue. Silica gel chromatography using a gradient of ethyl acetate/hexane (10-99%) provided 2-fluoro-N-(2-methoxypyridin-4-yl)-4,6-bis(trifluoromethyl)benzamide (1.2 g, 67%) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.42 (d, J=8.6 Hz, 1H), 8.17 (s, 1H), 8.13 (dd, J=5.4, 0.9 Hz, 1H), 7.14-7.10 (m, 2H), 3.85 (s, 3H) ppm. ESI-MS m/z calc. 382.05. found 383.1 (M+1)+; Retention time: 1.48 minutes (3 minutes run).

Workup

  1. washwashed with 50% saturated sodium bicarbonate solution (2×20 mL), water, and brine
  2. dry with materialThe solution was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customdried down to a purple residue

Sources & evidence

ORD record
ord-89ae1ca64de44dcd9fd0febf688fd759
Source dataset
uspto-grants-2016_07
Patent number
US09393235B2

Reaction notes

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