Sodium hydride → 2-(2-Methyl-8-trifluoromethoxy-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol

HRID 1630585Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1630585
[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[O:22]1[CH2:24][CH:23]1[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[N:6]([CH2:24][CH:23]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[OH:22])[C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]([F:17])([F:15])[F:16])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 594549332-methyl-8-trifluoromethoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Produkt 1

HCID 682836372-(2-Methyl-8-trifluoromethoxy-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 2-methyl-8-trifluoromethoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 g, 3.70 mmol) in DMF (10 mL) was added sodium hydride (445 mg, 11.12 mmol) under nitrogen at 0° C. After stirring for 10 min, 4-(oxiran-2-yl)pyridine (806 g, 6.66 mmol) was added dropwise under nitrogen and the reaction mixture was stirred at RT for 12 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was poured into ice-cold water and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (5×50 mL) and dried over anhydrous sodium sulfate, concentrated and re-crystallized in diethyl ether to yield 2-(2-methyl-8-trifluoromethoxy-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.58 (d, 2H), 7.17-7.21 (m, 4H), 7.0 (d, 1H), 4.6 (m, 1H), 4.0 (m, 2H), 3.38 (dd, 2H), 2.8 (m, 1H), 2.7 (m, 2H), 2.6 (m, 1H), 2.18 (s, 3H). Separation by chiral HPLC provides enantiomers II-67a-b.

Aufarbeitung

  1. stirringthe reaction mixture was stirred at RT for 12 h
  2. customThe progress of reaction
  3. additionThe reaction mixture was poured into ice-cold water
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe combined organic layer was washed with water (5×50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customre-crystallized in diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-9976781a9f664bb7aa2f79792f67a049
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791132B2

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