Dichloromethane → N-[5-chloro-2-(1-piperidinyl)phenyl]isonicotinamide

HRID 2195655

Reaction equation

HRID 2195655 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.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[C:26]([CH:28]=1)[NH2:27]>CN(C)C1C=CN=CC=1.O>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N:29]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)=[C:26]([NH:27][C:2](=[O:9])[C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)[CH:28]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 2853175-Chloro-2-(piperidin-1-yl)anilineHCID 12262826Isonicotinoyl chloride hydrochloride

Product 1

HCID 23149647N-[5-chloro-2-(1-piperidinyl)phenyl]isonicotinamideYield 31.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent

Procedure

Isonicotinoyl chloride hydrochloride (350 mg, 1.96 mmol, commercially available product), triethylamine (740 μl, 5.30 mmol), and a catalytic amount of 4-(dimethylamino)pyridine were sequentially added at room temperature to a dichloromethane (10 ml) solution of 5-chloro-2-(1-piperidinyl)aniline (378 mg, 1.79 mmol), obtained as described in Referential Example 15-2. The resulting mixture was stirred for 19 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 (200 g, hexane/ethyl acetate=1/1). Thus, N-[5-chloro-2-(1-piperidinyl)phenyl]isonicotinamide (GIF-0341) (180 mg, 31.8%) 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 (200 g, hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-3342b7ef8a744ed4822622b15061f6c1
Source dataset
uspto-grants-2012_12
Patent number
US08338362B2

Linked notes

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