Ethyl Acetate → HCID 54589416, compound

HRID 588050Notes

Reaction equation

HRID 588050 reaction equation
Cl[C:2]1[N:17]=[CH:16][CH:15]=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=1)=[O:5].[NH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+].C(OC(=O)C)C>C1(C)C(C)=CC=CC=1>[CH2:25]([N:22]1[CH2:23][CH2:24][CH:19]([NH:18][C:2]2[N:17]=[CH:16][CH:15]=[CH:14][C:3]=2[C:4]([NH:6][C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=2)=[O:5])[CH2:20][CH2:21]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 4158521-Benzyl-4-piperidylamineHCID 1419048HCID 1419048, compound

Product 1

HCID 54589416HCID 54589416, compoundYield 66.5%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A solution of 2-chloro-(N-3-chlorophenyl)nicotinamide (280 mg, 1.05 mmol, 1.05 eq) prepared in Preparation Example 5, 4-amino-1-benzylpiperidine (1.0 mmol), and anhydrous potassium carbonate (1.3 mmol) in ortho-xylene was stirred for 24 hrs under reflux. The reaction mixture was cooled to a room temperature, added with ethylacetate, and extracted twice with 1N HCl. The aqueous layer thus formed was washed with 30 ml of ethylacetate, adjusted to a pH of about 9-10 by adding 2 N sodium hydroxide, and extracted two or three times with 20 ml of methylene chloride. The organic layer was dried over a desiccant, and concentrated in a reduced pressure. A desired fraction obtained by purification through silica gel chromatography was concentrated in a reduced pressure and dried in a vacuum to afford the title compound. Yield: 66.5% 1H NMR (DMSO-d6) δ8.15˜8.30 (m, 2H), 8.03 (d, 1H), 7.90 (s, 1H), 7.66 (d, 1H), 7.60 (d, 1H), 7.30˜7.60 (m, 6H), 7.19 (d, 1H), 6.70 (m, 1H), 4.10 (bs, 1H), 3.95 (s, 1H), 2.85˜3.15 (m, 2H), 2.70˜2.85 (m, 2H), 1.90˜2.15 (m, 2H), 1.60˜1.85 (m, 2H) ppm.

Workup

  1. temperatureunder reflux
  2. extractionextracted twice with 1N HCl
  3. customThe aqueous layer thus formed
  4. washwas washed with 30 ml of ethylacetate
  5. additionby adding 2 N sodium hydroxide
  6. extractionextracted two or three times with 20 ml of methylene chloride
  7. customThe organic layer was dried over a desiccant, and
  8. concentrationconcentrated in a reduced pressure
  9. customA desired fraction obtained by purification through silica gel chromatography
  10. concentrationwas concentrated in a reduced pressure
  11. customdried in a vacuum

Sources & evidence

ORD record
ord-1508274a7b3743a091afb8429a2044af
Source dataset
uspto-grants-2016_01
Patent number
US09227955B2

Reaction notes

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