Sodium hydride → HCID 71007925, Verbindung

HRID 1630487Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1630487
[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:15])[CH:10]=3)[NH:5][C:4]=2[CH2:3]1.[H-].[Na+].[CH3:18][C:19]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:21][O:20]1>CN(C=O)C>[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:15])[CH:10]=3)[N:5]([CH2:18][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)([OH:20])[CH3:21])[C:4]=2[CH2:3]1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 7571332,3,4,9-Tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indoleHCID 10261140Pyridine, 2-(2-methyloxiranyl)- (9CI)

Produkt 1

HCID 71007925HCID 71007925, VerbindungAusbeute 13,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2,6-Dimethyl-2,3,4,9-tetrahydro-1H-β-carboline (500 mg, 2.5 mmol) was dissolved in 20 mL DMF and stirred for 10 min at RT. Sodium hydride (180 mg, 7.5 mmol) was added portionwise at RT and the mixture stirred for 10 min. 2-(2-Methyl-oxiranyl)-pyridine (472 mg, 3.5 mmol) was added dropwise at the same temperature and stirred for 12 h at RT. The reaction was monitored by TLC & LCMS. After consumption of starting material, the reaction mixture was quenched with ice water and extracted with EtOAc (3×100 mL). The combined organic layer was washed with water (3×100 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated and the residue was crystallized in hexane to obtain 115 mg of 1-(2,6-dimethyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-2-pyridin-2-yl-propan-2-ol. 1HNMR (CDCl3, freebase) δ (ppm): 8.51 (d,1H), 7.65 (t,1H), 7.29 (d, 1H), 7.22 (d,1H), 7.20 (s,1H), 6.95 (d,1H), 6.85 (d, 1H), 4.9 (bs,1H), 4.18 (s, 2H), 3.21 (dd, 2H), 2.77 (m, 2H), 2.69 (m, 2H), 2.42 (d, 6H), 1.63 (s, 3H). Separation by chiral HPLC provided enantiomers 16a and 16b. Optical rotations: Compound 16a, (−)5.77(c 0.52, Chloroform, 98.11% HPLC purity); Compound 16b, (+)5.85 (c 0.51, Chloroform, 98.06% HPLC purity).

Aufarbeitung

  1. stirringthe mixture stirred for 10 min
  2. stirringstirred for 12 h at RT
  3. customAfter consumption of starting material
  4. customthe reaction mixture was quenched with ice water
  5. extractionextracted with EtOAc (3×100 mL)
  6. washThe combined organic layer was washed with water (3×100 mL)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customthe residue was crystallized in hexane

Quellen und Nachweise

ORD-Eintrag
ord-b366e2470bcf4050bd6e07268f5f0786
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791132B2

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