Sodium Carbonate → cis-4-amino-5-chloro-N-[1-[2-[(3-cyano-2-pyridinyl)amino]ethyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide

HRID 654179Notes

Reaction equation

HRID 654179 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[C:30]([Cl:31])=[CH:29][C:14]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][NH2:26])[CH2:20][C@H:19]2[O:27][CH3:28])=[O:16])=[C:13]([O:32][CH3:33])[CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C(=O)C>ClCCl>[NH2:10][C:11]1[C:30]([Cl:31])=[CH:29][C:14]([C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][NH:26][C:2]3[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=3)[CH2:20][C@H:19]2[O:27][CH3:28])=[O:16])=[C:13]([O:32][CH3:33])[CH:12]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 810792-ChloronicotinonitrileHCID 14854954cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide

Product 1

HCID 67915679cis-4-amino-5-chloro-N-[1-[2-[(3-cyano-2-pyridinyl)amino]ethyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamideYield 21.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1.66 parts of 2-chloro-3-pyridinecarbonitrile, 4.28 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide, 1.3 parts of sodium carbonate and 22.5 parts of N,N-dimethylacetamide was stirred for 20 hours at 70° C. The reaction mixture was taken up in dichloromethane. The organic layer was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 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 1.19 parts (21.6%) of cis-4-amino-5-chloro-N-[1-[2-[(3-cyano-2-pyridinyl)amino]ethyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 134.0° C. (compound 32).

Workup

  1. washThe organic layer was washed with water
  2. customdried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was crystallized from acetonitrile
  10. filtrationThe product was filtered off
  11. customdried

Sources & evidence

ORD record
ord-b90ddc5629964903bcc7df33eba5bd0d
Source dataset
uspto-grants-1992_07
Patent number
US05130312

Reaction notes

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