Potassium Iodide → cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-[(3-methyl-2-pyrazinyl)amino]ethyl]-4-piperidinyl]benzamide

HRID 1165044Notes

Reaction equation

HRID 1165044 reaction equation
Br[C:2]1[C:7]([CH3:8])=[N:6][CH:5]=[CH:4][N:3]=1.[I-].[K+].[NH2:11][C:12]1[C:31]([Cl:32])=[CH:30][C:15]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][NH2:27])[CH2:21][C@H:20]2[O:28][CH3:29])=[O:17])=[C:14]([O:33][CH3:34])[CH:13]=1.[OH-].[NH4+]>ClCCl.O>[NH2:11][C:12]1[C:31]([Cl:32])=[CH:30][C:15]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][NH:27][C:2]3[C:7]([CH3:8])=[N:6][CH:5]=[CH:4][N:3]=3)[CH2:21][C@H:20]2[O:28][CH3:29])=[O:17])=[C:14]([O:33][CH3:34])[CH:13]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 14923Ammonium HydroxideHCID 124575132-Bromo-3-methylpyrazineHCID 14854954cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide

Product 1

HCID 14855021cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-[(3-methyl-2-pyrazinyl)amino]ethyl]-4-piperidinyl]benzamideYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 8.56 parts of 2-bromo-3-methylpyrazine and 0.1 parts of potassium iodide was pulverized and 2 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide were added. The whole was stirred for 3 hours at 120° C. The reaction mixture was taken up in dichloromethane and water and made alkaline with ammonium hydroxide. The organic layer was separated, washed with water, 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 first fractions was collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 1.95 parts (36%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-[(3-methyl-2-pyrazinyl)amino]ethyl]-4-piperidinyl]benzamide; mp. 169.5° C. (compound 27).

Workup

  1. customThe organic layer was separated
  2. washwashed with water
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  8. customThe first fractions was collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from acetonitrile
  11. filtrationThe product was filtered off
  12. customdried

Sources & evidence

ORD record
ord-2aa1dc1a14994f909e4754acb813cc6a
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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