1-Hydroxybenzotriazole → N-[(3R,4R)-1-[(1-acetylpiperidin-4-yl)carbonyl]-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamide

HRID 1260948Notes

Reaction equation

HRID 1260948 reaction equation
Cl.[Cl:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([N:9]([C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@H:12]2[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH3:10])=[O:8])=[CH:5][CH:4]=1.[C:27]([N:30]1[CH2:35][CH2:34][CH:33]([C:36](O)=[O:37])[CH2:32][CH2:31]1)(=[O:29])[CH3:28].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(#N)C.O.C(N(CC)CC)C>[C:27]([N:30]1[CH2:31][CH2:32][CH:33]([C:36]([N:14]2[CH2:15][CH2:16][C@@H:11]([N:9]([CH3:10])[C:7](=[O:8])[C:6]3[CH:5]=[CH:4][C:3]([Cl:2])=[CH:26][CH:25]=3)[C@H:12]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:13]2)=[O:37])[CH2:34][CH2:35]1)(=[O:29])[CH3:28]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1172551-Acetylpiperidine-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 689287034-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide Monohydrochloride

Product 1

HCID 68870105N-[(3R,4R)-1-[(1-acetylpiperidin-4-yl)carbonyl]-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamideYield 44.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methylbenzamide monohydrochloride (200 mg) obtained in Example 137a, 1-acetylpiperidine-4-carboxylic acid (118 mg) and triethylamine (127 μL) in acetonitrile (5 mL) were added WSC.HCl (176 mg) and HOBt (140 mg), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 15→100% ethyl acetate/hexane) to give the title compound (113 mg, 44%) as a white powder.

Workup

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 15→100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9e178e8cce9443c1882d752b54beb177
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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