(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate → 2-[4-(7-Fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

HRID 1359070

Reaktionsgleichung

Reaktionsgleichung von HRID 1359070
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)(=O)=O)=CC=1.[F:28][C:29]1[CH:30]=[CH:31][CH:32]=[C:33]2[C:37]=1[NH:36][CH:35]=[C:34]2[C:38]1[CH2:39][CH2:40][NH:41][CH2:42][CH:43]=1>CS(C)=O>[F:28][C:29]1[CH:30]=[CH:31][CH:32]=[C:33]2[C:37]=1[NH:36][CH:35]=[C:34]2[C:38]1[CH2:39][CH2:40][N:41]([CH2:12][CH:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)[CH2:42][CH:43]=1

Komponenten

4

Edukt 2

HCID 11280604(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonateHCID 120834537-Fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Produkt 1

HCID 98888662-[4-(7-Fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-ylmethyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzene sulfonate (0.55 g, 1.4 mmole) and 7-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.80 g, 3.7 mmole) were combined in 10 mL of DMSO. The mixture was heated at 70-80° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was removed, washed with 400 mL portions of water and saturated brine, dried over sodium sulfate, filtered and concentrated to dryness under vacuum. The residue was column chromatographed on silica gel using 0-2% methanol/chloroform. The product fractions were concentrated in vacuum to give 0.39 g of the (S)-enantiomer of the title compound as a pale yellow solid (m.p. 205-210° C.), which retains 0.25 equivalents of chloroform.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between 400 mL each of ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe organic phase was removed
  4. washwashed with 400 mL portions of water and saturated brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under vacuum
  8. customchromatographed on silica gel using 0-2% methanol/chloroform
  9. concentrationThe product fractions were concentrated in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-179a50971f774740b18e12d74f2c7dee
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06599915B2

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