Methanol → N-(3-(trifluoromethyl)benzyl)-2-(2-(3-((methylamino)methyl)-benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide

HRID 625347Notes

Reaction equation

HRID 625347 reaction equation
[CH3:1][NH2:2].CO.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[F:13][C:14]([F:55])([F:54])[C:15]1[CH:16]=[C:17]([CH:51]=[CH:52][CH:53]=1)[CH2:18][NH:19][C:20](=[O:50])[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]2[CH:32]=[C:31]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:30]=[CH:29][C:28]=2[NH:39][C:40](=[O:49])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47]Br)[CH:42]=2)[CH:22]=1>CN(C)C=O.O>[F:13][C:14]([F:55])([F:54])[C:15]1[CH:16]=[C:17]([CH:51]=[CH:52][CH:53]=1)[CH2:18][NH:19][C:20](=[O:50])[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]2[CH:32]=[C:31]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:30]=[CH:29][C:28]=2[NH:39][C:40](=[O:49])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][NH:2][CH3:1])[CH:42]=2)[CH:22]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 4875Potassium IodideHCID 6329MethylamineHCID 11430Potassium CarbonateHCID 665867752-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

Product 1

HCID 66586835N-(3-(trifluoromethyl)benzyl)-2-(2-(3-((methylamino)methyl)-benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Into a 100-mL round-bottom flask, was placed a solution of methylamine in methanol (126 mg, 1.22 mmol, 4.00 equiv, 30%), potassium carbonate (124 mg, 0.90 mmol, 3.00 equiv), potassium iodide (10 mg, 0.06 mmol, 0.20 equiv), and a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (200 mg, 0.31 mmol, 1.00 equiv) in N,N-dimethylformamide (15 mL). The resulting solution was stirred for 3 h at 70° C. in an oil bath. The resulting solution was diluted with 250 mL of water. The resulting solution was extracted with 4×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×50 mL of brine, dried over sodium sulfate, and concentrated under vacuum. This resulted in 200 mg (crude) of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-((methylamino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide as a yellow solid.

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. extractionThe resulting solution was extracted with 4×20 mL of ethyl acetate
  3. washThe resulting mixture was washed with 2×50 mL of brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThis resulted in 200 mg (crude) of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-((methylamino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide as a yellow solid

Sources & evidence

ORD record
ord-09b03d101e7b460e808f73250e100ac4
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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