Tropic acid → cis-N-[2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]ethyl]-alpha-(hydroxymethyl)benzeneacetamide

HRID 2248633

反応式

HRID 2248633 の反応式
[OH:1][CH2:2][CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=O.C(Cl)(=O)OCC.[NH2:19][C:20]1[C:39]([Cl:40])=[CH:38][C:23]([C:24]([NH:26][C@H:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][NH2:35])[CH2:29][C@H:28]2[O:36][CH3:37])=[O:25])=[C:22]([O:41][CH3:42])[CH:21]=1>ClC(Cl)Cl.C(N(CC)CC)C>[NH2:19][C:20]1[C:39]([Cl:40])=[CH:38][C:23]([C:24]([NH:26][C@H:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][NH:35][C:4](=[O:6])[CH:3]([CH2:2][OH:1])[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:29][C@H:28]2[O:36][CH3:37])=[O:25])=[C:22]([O:41][CH3:42])[CH:21]=1

参加物

6

反応物 3

HCID 10726Tropic acidHCID 10928Ethyl chloroformateHCID 14854954HCID 14854954、化合物

生成物 1

HCID 86744372cis-N-[2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]ethyl]-alpha-(hydroxymethyl)benzeneacetamide収率 10%

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒2 回HCID 8471Triethylamine溶媒

実験手順

To a stirred suspension of 2.99 parts of α-(hydroxymethyl)benzeneacetic acid in 60 parts of trichloromethane were added dropwise first 1.82 parts of N,N-diethylethanamine and then 1.95 parts of ethyl carbonochloridate at a temperature below 5° C. Upon completion, stirring was continued for 45 minutes at this low temperature. The thus obtained solution was added dropwise to a solution of 5.35 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide in 45 parts of trichloromethane while the temperature was kept below 10° C. Upon completion, the whole was stirred for 20 hours at room temperature. The organic layer was washed with a sodium carbonate solution in water and with water, dried, filtered and evaporated. The residue was purified by column chromatography over silicia gel using a mixture of trichloromethane and methanol, saturated with ammonia, (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile and a few drops of water. The product was filtered off and dried in vacuo at 30° C., yielding 0.76 parts (10.0%) of cis-N-[2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]ethyl]-α-(hydroxymethyl)benzeneacetamide; mp. 114.0° C. (compound 87).

後処理

  1. customat a temperature below 5° C
  2. customwas kept below 10° C
  3. stirringUpon completion, the whole was stirred for 20 hours at room temperature
  4. washThe organic layer was washed with a sodium carbonate solution in water and with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silicia gel
  9. additiona mixture of trichloromethane and methanol
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from acetonitrile and a few drops of water
  13. filtrationThe product was filtered off
  14. customdried in vacuo at 30° C.

出典と根拠

ORDレコード
ord-ef442bdeb3294ba49f0865c098a3c89e
出典データセット
uspto-grants-1991_08
特許番号
US05041454

関連ノート

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