Fumaric Acid → 3-[1-(2-Methyl-7,8-Dihydro-1,6,9-Trioxa-3-Aza-Cyclopenta[a]Naphthalen-8-Ylmethyl)-1,2,3,6-Tetrahydro-Pyridin-4-Yl]-1H-Indole-5-Carbonitrile

HRID 1167162

反応式

HRID 1167162 の反応式
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:26][O:25][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[C:21]([CH3:24])[O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.[NH:27]1[CH2:32][CH:31]=[C:30]([C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[C:39]([C:42]#[N:43])[CH:40]=3)[NH:35][CH:34]=2)[CH2:29][CH2:28]1.C(O)(=O)/C=C/C(O)=O>CS(C)=O.C(O)C>[CH3:24][C:21]1[O:22][C:23]2=[C:15]3[C:16](=[CH:17][CH:18]=[C:19]2[N:20]=1)[O:25][CH2:26][CH:13]([CH2:12][N:27]1[CH2:28][CH:29]=[C:30]([C:33]2[C:41]4[C:36](=[CH:37][CH:38]=[C:39]([C:42]#[N:43])[CH:40]=4)[NH:35][CH:34]=2)[CH2:31][CH2:32]1)[O:14]3

参加物

6

反応物 3

HCID 444972Fumaric AcidHCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonateHCID 113335543-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile

生成物 1

HCID 98453653-[1-(2-Methyl-7,8-Dihydro-1,6,9-Trioxa-3-Aza-Cyclopenta[a]Naphthalen-8-Ylmethyl)-1,2,3,6-Tetrahydro-Pyridin-4-Yl]-1H-Indole-5-Carbonitrile

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 702Ethanol溶媒2 回

反応条件

温度
77.5 °C

実験手順

[(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl 4-methylbenzenesulfonate (0.60 g, 1.6 mmole) and 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole-5-carbonitrile (0.85 g, 3.8 mmole) were combined in 70 mL of DMSO under nitrogen. This solution was heated to 75-80° C. under nitrogen. After completion, the reaction was cooled to room temperature and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The crude residue was column chromatographed on silica gel using 30% hexanelethyl acetate to remove impurities. Ethyl acetate eluted the product, which was a yellow oil (0.24 g, 42%). The oil was crystallized from ethanol with the addition of a solution of fumaric acid (0.12 g, 1.02 mmole) in hot ethanol to give 0.20 g of the (S)-nantiomer of the title compound as a yellow solid difumarate.0.50 hydrate, m.p. 119° C. MS (ESI) m/z 427 (M+H)+.

後処理

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using 30% hexanelethyl acetate
  7. customto remove impurities
  8. washEthyl acetate eluted the product, which

出典と根拠

ORDレコード
ord-9ad994d13bc94762b8bb17ed6ba7d428
出典データセット
uspto-grants-2003_09
特許番号
US06617334B2

関連ノート

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