6-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → 8-[4-(6-Fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalene

HRID 1368357노트

반응식

HRID 1368357 반응식
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:22][C:21]3[C:16](=[CH:17][CH:18]=[C:19]4[NH:25][C:24]([C:26]([F:29])([F:28])[F:27])=[N:23][C:20]4=3)[O:15][CH2:14]2)(=O)=O)=CC=1.[F:30][C:31]1[CH:39]=[C:38]2[C:34]([C:35]([C:40]3[CH2:41][CH2:42][NH:43][CH2:44][CH:45]=3)=[CH:36][NH:37]2)=[CH:33][CH:32]=1>CS(C)=O.C(OCC)(=O)C>[F:30][C:31]1[CH:39]=[C:38]2[C:34]([C:35]([C:40]3[CH2:41][CH2:42][N:43]([CH2:12][CH:13]4[O:22][C:21]5[C:16](=[CH:17][CH:18]=[C:19]6[NH:25][C:24]([C:26]([F:29])([F:28])[F:27])=[N:23][C:20]6=5)[O:15][CH2:14]4)[CH2:44][CH:45]=3)=[CH:36][NH:37]2)=[CH:33][CH:32]=1

참가 물질

5

반응물 2

HCID 110530726-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 12071004[(8R)-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-8-yl]methyl 4-methylbenzenesulfonate

생성물 1

HCID 102990098-[4-(6-Fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalene

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
85 °C

실험 절차

A mixture of 0.50 g (1.2 mmole) of [(8R)-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-8-yl]methyl 4-methylbenzenesulfonate and 0.90 g (4.2 mmole) of 6-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole in 8.0 mL of DMSO was heated at 85° C. under nitrogen for 6 hours. The reaction was allowed to come to room temperature, diluted to 400 mL with ethyl acetate, washed with 400 mL portions of saturated aqueous sodium bicarbonate and water, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel with 1% methanol in chloroform as eluant and recrystallized from ethanol with the addition of 0.10 g of fumaric acid to give 0.16 g of the (S)-enantiomer of the title compound as a yellow solid hemifumarate, hydrate, m.p. 215-220° C.

후처리

  1. customto come to room temperature
  2. washwashed with 400 mL portions of saturated aqueous sodium bicarbonate and water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuum
  6. customchromatographed on silica gel with 1% methanol in chloroform as eluant
  7. customrecrystallized from ethanol with the addition of 0.10 g of fumaric acid

출처 및 근거

ORD 기록
ord-82d6c6e257e64efc868920c60df80471
출처 데이터셋
uspto-grants-2003_06
특허 번호
US06573283B2

반응 노트

불러오는 중…