Potassium Iodide → cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[4-oxo-4-(3-pyridinyl)butyl]-4-piperidinyl]benzamide

HRID 1165043Notes

Reaction equation

HRID 1165043 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)=[O:6].[NH2:13][C:14]1[C:30]([Cl:31])=[CH:29][C:17]([C:18]([NH:20][C@H:21]2[CH2:26][CH2:25][NH:24][CH2:23][C@H:22]2[O:27][CH3:28])=[O:19])=[C:16]([O:32][CH3:33])[CH:15]=1.C(N(CC)CC)C.[I-].[K+]>CN(C)C=O>[NH2:13][C:14]1[C:30]([Cl:31])=[CH:29][C:17]([C:18]([NH:20][C@H:21]2[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][CH2:4][C:5](=[O:6])[C:7]3[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=3)[CH2:23][C@H:22]2[O:27][CH3:28])=[O:19])=[C:16]([O:32][CH3:33])[CH:15]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamideHCID 124710054-Chloro-1-(pyridin-3-YL)butan-1-one

Product 1

HCID 14854942cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[4-oxo-4-(3-pyridinyl)butyl]-4-piperidinyl]benzamideYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3.47 parts of 4-chloro-1-(3-pyridinyl)-1-butanone, 4.5 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide, 1.94 parts of N,N-diethylethanamine, 0.1 parts of potassium iodide and 67.5 parts of N,N-dimethylformamide was stirred and heated for 48 hours at 70° C. The reaction mixture was evaporated. The residue was washed with a sodium carbonate solution in water and purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 1.36 parts (20%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[4-oxo-4-(3-pyridinyl)butyl]-4-piperidinyl]benzamide; mp. 166.2° C. (compound 1).

Workup

  1. customThe reaction mixture was evaporated
  2. washThe residue was washed with a sodium carbonate solution in water
  3. custompurified by column chromatography over silica gel using
  4. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  5. customThe pure fractions were collected
  6. customthe eluent was evaporated
  7. customThe residue was crystallized from acetonitrile
  8. filtrationThe product was filtered off
  9. customdried

Sources & evidence

ORD record
ord-8af85a6a6aec40089a0322c4685d4da3
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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