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

HRID 1477273Notes

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]=2[CH3:16])[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([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.C1(C)C=CC=CC=1>[F:28][C:25]([F:26])([F:27])[C:23]1[CH:22]=[C:21]([C:29]([CH3:33])([CH3:34])[C:30]([N:8]([C:5]2[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])[CH3:9])=[O:31])[CH:20]=[C:19]([C:18]([F:17])([F:35])[F:36])[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-(o-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
dry with materialdried over Na2SO4
filtrationfiltered
custompurified by flash chromatography

Sources & evidence

ORD record: ord-8ce4899c55c94b2fb802b06d621902ee
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403772B2

Reaction notes

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