3-(Trifluoromethyl)aniline → 3-(3-(pyrimidin-4-yl)pyridin-2-ylamino)-4-(trifluoromethyl)-N-(3-(trifluoromethyl)phenyl)benzamide

HRID 446316Notes

Reaction equation

HRID 446316 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:8]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=3[C:23]([F:26])([F:25])[F:24])[C:17](O)=[O:18])=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:3][CH:2]=1.[F:27][C:28]([F:37])([F:36])[C:29]1[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C(=O)(O)[O-].[Na+].CN(C=O)C>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:8]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=3[C:23]([F:26])([F:24])[F:25])[C:17]([NH:35][C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([C:28]([F:36])([F:37])[F:27])[CH:30]=3)=[O:18])=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:3][CH:2]=1

Participants

7

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669704063-(3-(Pyrimidin-4-yl)pyridin-2-ylamino)-4-(trifluoromethyl)benzoic acid

Product 1

HCID 585877793-(3-(pyrimidin-4-yl)pyridin-2-ylamino)-4-(trifluoromethyl)-N-(3-(trifluoromethyl)phenyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

3-(3-(Pyrimidin-4-yl)pyridin-2-ylamino)-4-(trifluoromethyl)benzoic acid (0.13 g, 0.36 mmol), 3-(trifluoromethyl)benzenamine (0.070 g, 0.43 mmol), TBTU (0.14 g, 0.43 mmol), DIPEA (0.13 ml, 0.72 mmol) were all mixed together in a 25 ml flask containing 3 ml of DMF. The mixture was stirred together at room temperature for 16 hours. The reaction was then diluted with an aqueous saturated solution of sodium bicarbonate and extracted with DCM. The organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and the purified by column chromatography on silica gel using a gradient of 30 to 80% EtOAc in hexanes to give 3-(3-(pyrimidin-4-yl)pyridin-2-ylamino)-4-(trifluoromethyl)-N-(3-(trifluoromethyl)phenyl)benzamide as an off-white solid. MS m/z=504 [M+1]+. Calc'd for C24H15F6N5O: 503.12.

Workup

  1. additionall mixed together in a 25 ml flask
  2. extractionextracted with DCM
  3. washThe organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate
  4. dry with materialThe organic layer was then dried with sodium sulfate
  5. customthe purified by column chromatography on silica gel using a gradient of 30 to 80% EtOAc in hexanes

Sources & evidence

ORD record
ord-edc14dfbb7cc4c2aa610e012907902ea
Source dataset
uspto-grants-2013_07
Patent number
US08476434B2

Reaction notes

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