Sodium Bicarbonate → cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(2-pyrazinylmethyl)-4-piperidinyl]-benzamide

HRID 345593Notes

Reaction equation

HRID 345593 reaction equation
[NH2:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[O:15][CH3:16])=[O:7])=[C:4]([O:20][CH3:21])[CH:3]=1.CS(O[CH2:27][C:28]1[CH:33]=[N:32][CH:31]=[CH:30][N:29]=1)(=O)=O.C(=O)([O-])O.[Na+]>CC(=O)C>[NH2:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:27][C:28]3[CH:33]=[N:32][CH:31]=[CH:30][N:29]=3)[CH2:11][C@H:10]2[O:15][CH3:16])=[O:7])=[C:4]([O:20][CH3:21])[CH:3]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamideHCID 15096999Pyrazin-2-ylmethyl methanesulfonate

Product 1

HCID 15096934cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(2-pyrazinylmethyl)-4-piperidinyl]-benzamide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

4.7 Parts of cis-4-amino-5-chloro-2methoxy-N-(3-methoxy-4-piperidinyl)benzamide were dissolved in 160 parts of 2-propanone. Then there were added successively 3.2 parts of [(2-pyrazinyl)methyl] methanesulfonate (ester) and 1.7 parts of sodium hydrogen carbonate. The whole was stirred and refluxed for 18 hours while nitrogen gas was introduced. The precipitated product was filtered off and the filtrate was 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 twice from acetonitrile, yielding 1.16 parts of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-(2-pyrazinylmethyl)-4-piperidinyl]-benzamide; mp. 203.5° C. (compound 144).

Workup

  1. temperaturerefluxed for 18 hours while nitrogen gas
  2. additionwas introduced
  3. filtrationThe precipitated product was filtered off
  4. customthe filtrate was evaporated
  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 twice from acetonitrile

Sources & evidence

ORD record
ord-8a6dfbf548e44cfd9f83ea97e28ecc1f
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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