Phenol → 1-{2-[1-(8-Methyl-2,3-dihydro-[1,4]-dioxino[2,3-f]quinolin-2-ylmethyl)-azetidin-3-yl]-ethyl}-1h-indole-6-carbonitrile

HRID 28488

Reaktionsgleichung

Reaktionsgleichung von HRID 28488
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][C@H:13]([CH2:16]OS(C4C=CC(Br)=CC=4)(=O)=O)[O:12][C:8]3=2)[N:3]=1.[C:28]([C:30]1[CH:38]=[C:37]2[C:33]([CH:34]=[CH:35][NH:36]2)=[CH:32][CH:31]=1)#[N:29].[C:39]1(O)[CH:44]=[CH:43][CH:42]=CC=1.[CH2:46]([N:48](CC)CC)C>CS(C)=O>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][CH:13]([CH2:16][N:48]4[CH2:46][CH:43]([CH2:44][CH2:39][N:36]5[C:37]6[C:33](=[CH:32][CH:31]=[C:30]([C:28]#[N:29])[CH:38]=6)[CH:34]=[CH:35]5)[CH2:42]4)[O:12][C:8]3=2)[N:3]=1

Komponenten

6

Edukt 4

HCID 996PhenolHCID 8471TriethylamineHCID 851461H-indole-6-carbonitrileHCID 20624762[(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonate

Produkt 1

HCID 104558061-{2-[1-(8-Methyl-2,3-dihydro-[1,4]-dioxino[2,3-f]quinolin-2-ylmethyl)-azetidin-3-yl]-ethyl}-1h-indole-6-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A solution of (2R)-4-bromobenzenesulfonic acid 8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-2-ylmethyl ester (0.21 g, 0.45 mmol) 1-(2-azetidin-3-yl-ethyl)-1H-indole-6-carbonitrile (0.11 g, 0.52 mmol), which was made in two steps from 6-cyanoindole according to the procedures described for Intermediates 40 and 41, and triethylamine (0.14 ml, 1 mmol) in dimethylsulfoxide (20 ml) was heated at 90° C. under nitrogen overnight. The reaction mixture was quenched with 1N sodium hydroxide and extracted with methylene chloride (3×80 ml). The organic layer was washed with water (3×50 ml), dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum. The crude oil was column chromatographed on silica gel (10% methanol-ethyl acetate). The product-containing fractions were concentrated in vacuum to give 0.08 g of the (S)-enantiomer of the title compound as a brown oil. The hydrochloride salt was prepared in ethyl acetate and collected as a yellow solid: yellow solid, m.p. 144° C. (dec).

Aufarbeitung

  1. customThe reaction mixture was quenched with 1N sodium hydroxide
  2. extractionextracted with methylene chloride (3×80 ml)
  3. washThe organic layer was washed with water (3×50 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customchromatographed on silica gel (10% methanol-ethyl acetate)
  8. concentrationThe product-containing fractions were concentrated in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-9f6d6acb928b48ab89798f17d4cc3194
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419986B2

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