Tropic acid → HCID 86744372, 화합물

HRID 1110397

반응식

HRID 1110397 반응식
[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

참가 물질

6

반응물 3

HCID 10726Tropic acidHCID 10928Ethyl chloroformateHCID 14854954HCID 14854954, 화합물

생성물 1

HCID 86744372HCID 86744372, 화합물수율 10%

시약·촉매·용매 2

HCID 6212Chloroform용매2회HCID 8471Triethylamine용매

실험 절차

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 silica 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).

후처리

  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 silica gel using
  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.

출처 및 근거

ORD 기록
ord-9f6afc79bc3f4c10a7e02cc5a4e440e5
출처 데이터셋
uspto-grants-1990_12
특허 번호
US04975439

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