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

HRID 2248626Notes

Reaction equation

HRID 2248626 reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][N:6]([CH2:9][CH3:10])[C:5]1=[O:11].[NH2:12][C:13]1[C:29]([Cl:30])=[CH:28][C:16]([C:17]([NH:19][C@H:20]2[CH2:25][CH2:24][NH:23][CH2:22][C@H:21]2[O:26][CH3:27])=[O:18])=[C:15]([O:31][CH3:32])[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[NH2:12][C:13]1[C:29]([Cl:30])=[CH:28][C:16]([C:17]([NH:19][C@H:20]2[CH2:25][CH2:24][N:23]([CH2:2][CH2:3][N:4]3[CH2:8][CH2:7][N:6]([CH2:9][CH3:10])[C:5]3=[O:11])[CH2:22][C@H:21]2[O:26][CH3:27])=[O:18])=[C:15]([O:31][CH3:32])[CH:14]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 3264961-(2-Chloroethyl)-3-ethyl-2-imidazolidinoneHCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamide

Product 1

HCID 67922947cis-4-amino-5-chloro-N-[1-[2-(3-ethyl-2-oxo-1-imidazolidinyl)ethyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamideYield 67.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2.21 parts of 1-(2-chloroethyl)-3-ethyl-2-imidazolidinone, 3.13 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide, 1.58 parts of sodium carbonate and 90 parts of N,N-dimethylformamide was stirred and heated for 48 hours at 70° C. The reaction mixture was evaporated. Water was added and the product was extracted twice with dichloromethane. The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The first fraction was collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 3.08 parts (67.8%) of cis-4-amino-5-chloro-N-[1-[2-(3-ethyl-2-oxo-1-imidazolidinyl)ethyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 152.8° C. (compound 1).

Workup

  1. customThe reaction mixture was evaporated
  2. additionWater was added
  3. extractionthe product was extracted twice with dichloromethane
  4. washThe combined extracts were washed with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol
  10. customThe first fraction was 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-83860c53e1b144d684f06ce12b87d370
Source dataset
uspto-grants-1991_08
Patent number
US05041454

Reaction notes

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