Water → 4-(7bR,11aS)-(1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-9(8H)-yl)-1-(4-fluorophenyl)-1-butanone

HRID 23258

Reaktionsgleichung

Reaktionsgleichung von HRID 23258
[CH2:1]1[N:12]2[C:13]3[C:9]([C@@H:10]4[CH2:17][NH:16][CH2:15][CH2:14][C@@H:11]42)=[CH:8][CH:7]=[CH:6][C:5]=3[CH2:4][S:3][CH2:2]1.Cl[CH2:19][CH2:20][CH2:21][C:22]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)=[O:23].C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1>[CH2:1]1[N:12]2[C:13]3[C:9]([C@@H:10]4[CH2:17][N:16]([CH2:19][CH2:20][CH2:21][C:22]([C:24]5[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=5)=[O:23])[CH2:15][CH2:14][C@@H:11]42)=[CH:8][CH:7]=[CH:6][C:5]=3[CH2:4][S:3][CH2:2]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 197503-(4-Fluorobenzoyl)propyl chlorideHCID 10198786(7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole

Produkt 1

HCID 206276564-(7bR,11aS)-(1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-9(8H)-yl)-1-(4-fluorophenyl)-1-butanoneAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of (7bR,11aS)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole from EXAMPLE 1 (80 mg, 0.32 mmol) in 1,4-dioxane (15 ml) at 25° C. was added 4-chloro-1-(4-fluorophenyl)butan-1-one (96 mg, 0.48 mmol), K2CO3 (100 mg, 0.72 mmol), and KI (32 mg, 0.19 mmol), respectively. The mixture was stirred at ambient temperature for 16 hours before H2O (10 mL) was added and then extracted with EtOAc (2×20 mL). The combined extracts were dried over magnesium sulfate, concentrated, and purified by flash chromatography to give the title compound of EXAMPLE 4 as an oil (88 mg, 67%). 1H NMR (CDCl3, 300 MHz): δ 8.01 (m, 2H), 7.15 (m, 2H), 6.96 (d, 1H, J=6.6 Hz), 6.92 (d, 1H, J 6.6 Hz), 3.82 (m, 2H), 3.25 (m, 2H), 3.19-2.60 (m, 8H), 2.42 (m, 2H), 1.95 (m, 5H). LRMS (ES)+: 411 (M+H)+.

Aufarbeitung

  1. additionwas added
  2. extractionextracted with EtOAc (2×20 mL)
  3. dry with materialThe combined extracts were dried over magnesium sulfate
  4. concentrationconcentrated
  5. custompurified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-392daa8f02f04d679d32ca7c2630892f
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06849619B2

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