Toluene → cis-4-amino-5-chloro-N-[1-[3-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide

HRID 1110398노트

반응식

HRID 1110398 반응식
[C:1]1(=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:10])O1.[NH2:12][C:13]1[C:33]([Cl:34])=[CH:32][C:16]([C:17]([NH:19][C@H:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][NH2:29])[CH2:22][C@H:21]2[O:30][CH3:31])=[O:18])=[C:15]([O:35][CH3:36])[CH:14]=1.CC1C=CC=CC=1>O>[NH2:12][C:13]1[C:33]([Cl:34])=[CH:32][C:16]([C:17]([NH:19][C@H:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][N:29]3[C:3](=[O:10])[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:1]3=[O:11])[CH2:22][C@H:21]2[O:30][CH3:31])=[O:18])=[C:15]([O:35][CH3:36])[CH:14]=1

참가 물질

5

반응물 3

HCID 1140TolueneHCID 6811Phthalic AnhydrideHCID 14854959HCID 14854959, 화합물

생성물 1

HCID 67922873cis-4-amino-5-chloro-N-[1-[3-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide수율 42%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A mixture of 1.85 parts of 1,3-isobenzofurandione, 4.4 parts of cis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 45 parts of methylbenzene was stirred for 3 hours at reflux temperature, using a water separator. The reaction mixture was evaporated. The residue was taken up in trichloromethane. The organic phase was washed with a saturate solution of sodium carbonate and 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, (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 2.5 parts (42,4%) of cis-4-amino-5-chloro-N-[1-[3-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 208.2° C. (compound 88).

후처리

  1. temperatureat reflux temperature
  2. customThe reaction mixture was evaporated
  3. washThe organic phase was washed with a saturate solution of sodium carbonate and water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrile
  12. filtrationThe product was filtered off
  13. customdried

출처 및 근거

ORD 기록
ord-79e66662825a4780a508323e93826655
출처 데이터셋
uspto-grants-1990_12
특허 번호
US04975439

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