5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → 8-[4-(5-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 584593ノート

反応式

HRID 584593 の反応式
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:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][CH:35]=[C:34]2[C:40]1[CH2:41][CH2:42][NH:43][CH2:44][CH:45]=1>CS(C)=O.C(OCC)(=O)C>[F:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][CH:35]=[C:34]2[C:40]1[CH2:41][CH2:42][N:43]([CH2:12][CH: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)[CH2:44][CH:45]=1

参加物

5

反応物 2

HCID 113449595-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

生成物 1

HCID 102272018-[4-(5-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収率 79.4%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

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 1.0 g (4.6 mmole) of 5-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole in 5.0 mL of DMSO was heated at 85° C. under nitrogen for 6 hours. The reaction was allowed to come to room temperature, diluted to 250 mL with ethyl acetate, washed with 250 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 the product fractions concentrated in vacuum to give 0.45 g of the desired compound as the free base. Recrystallization from ethanol with the addition of 0.11 g of fumaric acid gave 0.25 g of the (S)-enantiomer of the title compound as a yellow solid hemifumarate, m.p. 236-238° C.

後処理

  1. customto come to room temperature
  2. washwashed with 250 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. concentrationthe product fractions concentrated in vacuum

出典と根拠

ORDレコード
ord-d50e625a4660469e862da15b768c8ced
出典データセット
uspto-grants-2005_08
特許番号
US06927226B2

反応ノート

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