3-Hydroxypyridine → HCID 67915842, compound

HRID 1165054Notes

Reaction equation

HRID 1165054 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([OH:7])[CH:2]=1.[H-].[Na+].[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]Cl)[CH2:20][C@H:19]2[O:27][CH3:28])=[O:16])=[C:13]([O:32][CH3:33])[CH:12]=1>CN(C)C=O>[OH2:7].[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][O:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH2:20][C@H:19]2[O:27][CH3:28])=[O:16])=[C:13]([O:32][CH3:33])[CH:12]=1

Participants

5

Reactant 3

HCID 79713-HydroxypyridineHCID 24758Sodium hydrideHCID 67915660HCID 67915660, compound2×

Product 1

HCID 67915842HCID 67915842, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 1.43 parts of 3-pyridinol in 135 parts of N,N-dimethylformamide were added 0.77 parts of a sodium hydride solution 50% at a temperature below 30° C. The whole was stirred first for 1.5 hours at room temperature and then for 10 minutes at 60° C. After cooling with ice water, a solution of 5.64 parts of cis-4-amino-5-chloro-N-[1-(2-chloro-ethyl)-3-methoxy-4-piperidinyl]-2-methoxybenzamide in 135 parts of N,N-dimethylformamide was added dropwise at a temperature between 17°-20° C. Upon completion, stirring was continued first overnight at room temperature and then for 3 hours at 50° C. Another portion of 5.64 parts of cis-4-amino-5-chloro-N-[1-(2-chloroethyl)-3-methoxy-4-piperidinyl]-2-methoxybenzamide was added and the mixture was stirred for 1 hour at 50° C. After the addition of crushed ice, the reaction mixture was concentrated. The aqueous phase was extracted with trichloromethane. The combined organic layers were 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 solidified on scratching in 2,2'-oxybispropane. The product was filtered off and dried, yielding 1.38 parts (20%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-(3-pyridinyloxy)ethyl]-4-piperidinyl]benzamide monohydrate; mp. 90.2° C. (compound 47).

Workup

  1. waitfor 10 minutes at 60° C
  2. stirringUpon completion, stirring
  3. waitwas continued first overnight at room temperature
  4. waitfor 3 hours at 50° C
  5. stirringthe mixture was stirred for 1 hour at 50° C
  6. additionAfter the addition of crushed ice
  7. concentrationthe reaction mixture was concentrated
  8. extractionThe aqueous phase was extracted with trichloromethane
  9. customThe combined organic layers were dried
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by column chromatography over silica gel using
  13. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  14. customThe pure fractions were collected
  15. customthe eluent was evaporated
  16. filtrationThe product was filtered off
  17. customdried

Sources & evidence

ORD record
ord-71be09d655ef44d7a43799527cb2ca41
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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