Sodium cyanoborohydride → 6-[4-(3-Propyl-piperidin-1-ylmethyl)-phenoxy]-nicotinamide

HRID 131043Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 131043
[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][CH2:15][CH3:16])[CH2:9]2)=[CH:5][CH:4]=1.[H][H].C(C1C=CC(OC2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][N:29]=2)=CC=1)=O.[BH3-]C#N.[Na+].CC(O)=[O:44].CO>[OH-].[OH-].[Pd+2].C(O)C>[CH2:14]([CH:10]1[CH2:11][CH2:12][CH2:13][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][C:1]3[CH:35]=[CH:34][C:31]([C:32]([NH2:33])=[O:44])=[CH:30][N:29]=3)=[CH:18][CH:17]=2)[CH2:9]1)[CH2:15][CH3:16]

Komponenten

8

Edukt 5

HCID 5003444Sodium cyanoborohydrideHCID 10129899Acetic acid methanolHCID 471502166-(4-Formylphenoxy)nicotinonitrile2×HCID 597300471-(4-Methoxy-benzyl)-3-propyl-piperidineHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 597301556-[4-(3-Propyl-piperidin-1-ylmethyl)-phenoxy]-nicotinamideAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 702EthanolLösungsmittel

Versuchsvorschrift

Combine 1-(4-Methoxy-benzyl)-3-propyl-piperidine (105.2 mg, 0.43 mmol), Ethanol (50 mL), 20% Pd(OH)2/C (75.0 mg), and a Hydrogen at 30° C. under 50-60 psi for 12 hours on a Parr shaker. Filter the reaction mixture and then add 5% AcOH/MeOH (3 mL), 6-(4-Formyl-phenoxy)-nicotinonitrile (Intermediate 51) (40.0 mg, 0.31 mmol), and NaCNBH3 (83.7 mg, 0.34 mmol). Stir the reaction at room temperature for 72 hours and then concentrate the reaction mixture under reduced pressure. Add the reaction mixture to an SCX Column (2 g), wash with methanol, and elute with 1N NH3 MeOH. Concentrate under reduced pressure and flash chromatograph using 3% 1N NH3 MeOH in CH2Cl2 to give 19.8 mg (18% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 0.8-0.9 (4H, m), 1.0-1.4 (5H, m), 1.5-1.8 (4H, m), 1.9-2.1 (1H, br s), 2.8-3.0 (2H, br s), 3.4-3.7 (2H, br d), 6.9 (1H, d), 7.1 (2H, d), 7.3-7.5 (2H, m), 8.1 (1H, d), 8.6 (1H, s); MS m/z 354 (M+1).

Aufarbeitung

  1. filtrationFilter the reaction mixture
  2. customthe reaction at room temperature for 72 hours
  3. concentrationconcentrate the reaction mixture under reduced pressure
  4. additionAdd the reaction mixture to an SCX Column (2 g)
  5. washwash with methanol
  6. washelute with 1N NH3 MeOH
  7. concentrationConcentrate under reduced pressure and flash chromatograph

Quellen und Nachweise

ORD-Eintrag
ord-320b76e2d7264743862da55402f2fbaa
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381719B2

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