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

HRID 654177ノート

反応式

HRID 654177 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-1fdb2c7c0ec144d4a94a84b3e444ad53
出典データセット
uspto-grants-1992_07
特許番号
US05130312

反応ノート

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