Dimethylformamide → trans-4-amino-5-chloro-N-[3-hydroxy-1-[4-oxo-4-(1-pyrrolidinyl)butyl]-4-piperidinyl]-2-methoxybenzamide

HRID 2248628Notes

Reaction equation

HRID 2248628 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6].CN(C)C=O.[NH2:17][C:18]1[C:33]([Cl:34])=[CH:32][C:21]([C:22]([NH:24][C@@H:25]2[CH2:30][CH2:29][NH:28][CH2:27][C@H:26]2[OH:31])=[O:23])=[C:20]([O:35][CH3:36])[CH:19]=1>C(N(CC)CC)C>[NH2:17][C:18]1[C:33]([Cl:34])=[CH:32][C:21]([C:22]([NH:24][C@@H:25]2[CH2:30][CH2:29][N:28]([CH2:2][CH2:3][CH2:4][C:5](=[O:6])[N:7]3[CH2:11][CH2:10][CH2:9][CH2:8]3)[CH2:27][C@H:26]2[OH:31])=[O:23])=[C:20]([O:35][CH3:36])[CH:19]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 3040794-Chloro-1-(pyrrolidin-1-yl)butan-1-oneHCID 67922711trans-4-amino-5-chloro-N-(3-hydroxy-4-piperidinyl)-2-methoxybenzamide

Product 1

HCID 67922971trans-4-amino-5-chloro-N-[3-hydroxy-1-[4-oxo-4-(1-pyrrolidinyl)butyl]-4-piperidinyl]-2-methoxybenzamideYield 47.8%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 3.00 parts of 1-(4-chloro-1-oxobutyl)pyrrolidine in 67.5 parts of N,N-dimethylformamide were added 1.93 parts of trans-4-amino-5-chloro-N-(3-hydroxy-4-piperidinyl)-2-methoxybenzamide and 1.5 parts of N,N-diethylethanamine and the whole was stirred for 18 hours at 70° C. The reaction mixture was evaporated and the residue was taken up in a sodium carbonate solution in water. The product was extracted with trichloromethane. The extract 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, saturate with ammonia, (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 2.1 parts (47.8%) of trans-4-amino-5-chloro-N-[3-hydroxy-1-[4-oxo-4(1-pyrrolidinyl)butyl]-4-piperidinyl]-2-methoxybenzamide; mp. 174.7° C. (compound 15).

Workup

  1. customThe reaction mixture was evaporated
  2. extractionThe product was extracted with trichloromethane
  3. washThe extract was washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol
  9. concentrationsaturate with ammonia, (90:10 by volume) as eluent
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from acetonitrile
  13. filtrationThe product was filtered off
  14. customdried

Sources & evidence

ORD record
ord-97ea9ea542ff4efb9c71f79b080a9393
Source dataset
uspto-grants-1991_08
Patent number
US05041454

Reaction notes

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