Dichloromethane → N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]nicotinamide

HRID 2410287Notes

Reaction equation

HRID 2410287 reaction equation
Cl.[C:2](Cl)(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=1.C(N(CC)CC)C.ClCCl.[N:21]1([C:27]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][C:28]=2[NH2:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>O>[N:21]1([C:27]2[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][C:28]=2[NH:29][C:2](=[O:9])[C:3]2[CH:8]=[CH:7][CH:6]=[N:5][CH:4]=2)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 6947562-(Piperidin-1-yl)-5-(trifluoromethyl)aniline

Product 1

HCID 953304N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]nicotinamideYield 45.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Nicotinoyl chloride hydrochloride (122 mg, 0.685 mmol, commercially available product) and triethylamine (250 μl, 1.79 mmol) were sequentially added at 0° C. to a dichloromethane (5 ml) solution of 2-(1-piperidinyl)-5-(trifluoromethyl)aniline (152 mg, 0.622 mmol), obtained as described in Referential Example 1-2. The resulting mixture was warmed to room temperature and stirred for 16.5 hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15 g, hexane/ethyl acetate=1.5/1-1/1). Thus, N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]nicotinamide (GIF-0343) (98.4 mg, 45.3%) was yielded as a colorless solid.

Workup

  1. customobtained
  2. extractionthe resulting mixture was extracted three times with ethyl acetate
  3. washThe obtained organic layer was washed with a saturated sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (15 g, hexane/ethyl acetate=1.5/1-1/1)

Sources & evidence

ORD record
ord-237467421fc24a43bc346e14b80c1767
Source dataset
uspto-grants-2014_08
Patent number
US08816089B2

Reaction notes

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