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

HRID 654180Notes

Reaction equation

HRID 654180 reaction equation
Cl[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:8][C:9]1[C:29]([Cl:30])=[CH:28][C:12]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][NH2:25])[CH2:18][C@H:17]2[O:26][CH3:27])=[O:14])=[C:11](OC)[CH:10]=1.[C:33](=O)([O-])[O-:34].[Na+].[Na+]>CN(C)C(=O)C>[NH2:8][CH:9]1[C:29]([Cl:30])([O:34][CH3:33])[CH:28]=[C:12]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][NH:25][C:2]3[N:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[CH2:18][C@H:17]2[O:26][CH3:27])=[O:14])[CH:11]=[CH:10]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 14854959HCID 14854959, compound

Product 1

HCID 67915924cis-4-amino-5-chloro-5-methoxy-N-[3-methoxy-1-[3-(2-pyrimidinylamino)propyl]-4-piperidinyl]benzamideYield 35%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1.17 parts of 2-chloropyrimidine, 5.56 parts of cis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 2.7 parts of N,N-dimethylacetamide was stirred for 6.5 hours at 90° C. After cooling, a sodium carbonate solution was added. The product was extracted with dichloromethane. The extract was 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 pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane. The product was filtered off and dried, yielding 2.4 parts (35%) of cis-4-amino-5-chloro-5-methoxy-N-[3-methoxy-1-[3-(2-pyrimidinylamino)propyl]-4-piperidinyl]benzamide; mp. 158.5° C. (compound 36).

Workup

  1. temperatureAfter cooling
  2. extractionThe product was extracted with dichloromethane
  3. customThe extract was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane
  11. filtrationThe product was filtered off
  12. customdried

Sources & evidence

ORD record
ord-f2e804d24cbd41608327a60fe1689784
Source dataset
uspto-grants-1992_07
Patent number
US05130312

Reaction notes

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