Sodium Carbonate → cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(3-pyridinylmethyl)-4-piperidinyl]benzamide

HRID 345589Notes

Reaction equation

HRID 345589 reaction equation
Cl.Cl[CH2:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1.[NH2:10][C:11]1[C:27]([Cl:28])=[CH:26][C:14]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][NH:21][CH2:20][C@H:19]2[O:24][CH3:25])=[O:16])=[C:13]([O:29][CH3:30])[CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[NH2:10][C:11]1[C:27]([Cl:28])=[CH:26][C:14]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][N:21]([CH2:3][C:4]3[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=3)[CH2:20][C@H:19]2[O:24][CH3:25])=[O:16])=[C:13]([O:29][CH3:30])[CH:12]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamide

Product 1

HCID 15096906cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(3-pyridinylmethyl)-4-piperidinyl]benzamideYield 64.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2.8 parts of 3-(chloromethyl)pyridine hydrochloride, 4.7 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4piperidinyl)benzamide, 5.3 parts of sodium carbonate and 68 of N,N-dimethylformamide was stirred for 5 hours at about 60° C. The reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated. The solid residue was 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 eluent was evaporated. The residue was crystallized from ethanol. The product was filtered off and dried, yielding 3.84 parts (64.2%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(3-pyridinylmethyl)-4-piperidinyl]benzamide; mp. 188.9° C. (compound 91).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. customThe filtrate was evaporated
  4. customThe solid residue was purified by column-chromatography over silica gel using
  5. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  6. customThe pure fractions were collected
  7. customeluent was evaporated
  8. customThe residue was crystallized from ethanol
  9. filtrationThe product was filtered off
  10. customdried

Sources & evidence

ORD record
ord-0d8640e88e6d4b08b193657e6c56ecbc
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

Loading…