Dichloromethane → N-[2-(4-morpholinyl)-5-(trifluoromethyl)phenyl]isonicotinamide

HRID 2195642Notes

Reaction equation

HRID 2195642 reaction equation
Cl.[C:2](Cl)(=[O:9])[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.ClCCl.[NH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1[N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>O>[N:32]1([C:23]2[CH:24]=[CH:25][C:26]([C:28]([F:29])([F:31])[F:30])=[CH:27][C:22]=2[NH:21][C:2](=[O:9])[C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 136624N-(2-Amino-4-(trifluoromethyl)phenyl)morpholineHCID 12262826Isonicotinoyl chloride hydrochloride

Product 1

HCID 2117018N-[2-(4-morpholinyl)-5-(trifluoromethyl)phenyl]isonicotinamideYield 23.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Isonicotinoyl chloride hydrochloride (320 mg, 1.80 mmol, commercially available product) and triethylamine (480 μl, 3.44 mmol) were sequentially added at 0° C. to a dichloromethane (5 ml) solution of 4-[2-amino-4-(trifluoromethyl)phenyl]morpholine (196 mg, 0.796 mmol), obtained as described in Referential Example 5-2. The resulting mixture was warmed to room temperature and stirred for 60 hours. Water was added to the mixture, and the resulting mixture was extracted three times with dichloromethane. 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 (30 g, hexane/ethyl acetate=2/1). Thus, N-[2-(4-morpholinyl)-5-(trifluoromethyl)phenyl]isonicotinamide (GIF-0346) (65.1 mg, 23.2%) was yielded as a colorless solid.

Workup

  1. customobtained
  2. extractionthe resulting mixture was extracted three times with dichloromethane
  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 (30 g, hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-ebaf6c13ad9941b4acd5ef62d4348a91
Source dataset
uspto-grants-2012_12
Patent number
US08338362B2

Reaction notes

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