Hydrochloric Acid → Alosetron

HRID 1588272노트

반응식

HRID 1588272 반응식
[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:11](=[O:15])[NH:12][CH2:13][CH2:14][C:3]1=2.[H-].[Na+].Cl[CH2:19][C:20]1[N:21]=[CH:22][N:23](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C:24]=1[CH3:25].Cl.[OH-].[Na+]>C(COC)OC.O>[NH3:2].[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]2[C:11](=[O:15])[N:12]([CH2:19][C:20]3[N:21]=[CH:22][NH:23][C:24]=3[CH3:25])[CH2:13][CH2:14][C:3]1=2

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 110469654-(Chloromethyl)-5-methyl-1-trityl-1H-imidazoleHCID 117902131H-Pyrido(4,3-b)indol-1-one, 2,3,4,5-tetrahydro-5-methyl-

생성물 2

HCID 222AmmoniaHCID 2099Alosetron수율 119.7%

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

A suspension of 2,3,4,5-tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one (400 mg) in dry dimethoxyethane (50 ml) was treated with sodium hydride (60% dispersion in oil; 100 mg), and the mixture was stirred at 60° under nitrogen for 6 h. 4-(Chloromethyl)-5-methyl-1-(triphenylmethyl)-1H-imidazole (474 mg) was added and the reaction mixture was stirred at 60° under nitrogen overnight. 2N Hydrochloric acid (10 ml) and water (10 ml) were then added, and the mixture was heated at reflux for 6 h. After cooling, the mixture was basified with 2N sodium hydroxide and the resulting mixture was extracted with ethyl acetate (2×50 ml). The combined, dried organic extracts were concentrated onto flash column chromatography (FCC) silica and purified by FCC eluting with dichloromethane:ethanol: 0.88 ammonia (150:8:1) to give the title compound (352 mg) as a solid, t.l.c. (dichloromethane:ethanol:0.88 ammonia 100:8:1) Rf 0.28. 1H-N.m.r. (DMSO-d6): δ 2.2 (3H,s), 3.04 (2H,t), 3.62 (2H,t), 3.72 (3H,s), 4.53 (2H,s), 7.1-7.28 (2H,m), 7.43 (1H,s), 7.47-7.55 (1H,dd), 7.94-8.03 (1H,dd).

후처리

  1. stirringthe reaction mixture was stirred at 60° under nitrogen overnight
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 6 h
  4. temperatureAfter cooling
  5. extractionthe resulting mixture was extracted with ethyl acetate (2×50 ml)
  6. concentrationdried organic extracts were concentrated onto flash column chromatography (FCC) silica
  7. custompurified by FCC
  8. washeluting with dichloromethane

출처 및 근거

ORD 기록
ord-8e34c47b3afc426a9e564618878bbfa8
출처 데이터셋
uspto-grants-1993_06
특허 번호
US05221687

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