Sodium Bicarbonate → 2-(3,5-bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-tolyl)pyridin-3-yl)-N,2-dimethylpropanamide

HRID 340425Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][CH3:9])=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2C)[CH:3]=1.[F:17][C:18]([F:36])([F:35])[C:19]1[CH:20]=[C:21]([C:29]([CH3:34])([CH3:33])[C:30](Cl)=[O:31])[CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1.[C:37]([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.C1(C)C=CC=CC=1>[F:17][C:18]([F:36])([F:35])[C:19]1[CH:20]=[C:21]([C:29]([CH3:34])([CH3:33])[C:30]([N:8]([C:5]2[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[C:10]2[CH:11]=[CH:12][C:13]([CH3:37])=[CH:14][CH:15]=2)[CH3:9])=[O:31])[CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To the solution of 6-chloro-N-methyl-4-(o-tolyl)pyridin-3-amine (18.87 g, 81.3 mmol) and DMAP (29.8 g, 243.9 mmol) in 200 mL of anhydrous toluene was added the solution of 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride (28.5 g, 89.4 mmol) in toluene under N2 atmosphere. The solution was heated at 120° C. for 23 hrs. Cooled to room temperature, poured into 1 L of 5% aq. NaHCO3 solution, and extracted with EtOAc twice. The combined organic phases were washed by water and brine consecutively, dried. over Na2SO4, filtered and purified by flash chromatography to afford 35 g 2-(3,5-bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-tolyl)pyridin-3-yl)-N,2-dimethylpropanamide as a white solid (Yield: 83.9%).

Workup

temperatureCooled to room temperature
extractionextracted with EtOAc twice
washThe combined organic phases were washed by water and brine consecutively
customdried
filtrationover Na2SO4, filtered
custompurified by flash chromatography

Sources & evidence

ORD record: ord-6f59a08956684dc38039973baa936cb7
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895586B2

Reaction notes

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