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

HRID 131047Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 131047
[C:1](=[C:4]1[CH2:9][CH2:8][CH2:7][N:6]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:5]1)([CH3:3])[CH3:2].[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>[CH:1]([CH:4]1[CH2:9][CH2:8][CH2:7][N:6]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:35]=[CH:34][C:31]([C:32]([NH2:33])=[O:44])=[CH:30][N:29]=3)=[CH:13][CH:12]=2)[CH2:5]1)([CH3:3])[CH3:2]

Komponenten

8

Edukt 5

HCID 5003444Sodium cyanoborohydrideHCID 10129899Acetic acid methanolHCID 471502166-(4-Formylphenoxy)nicotinonitrile2×HCID 597300293-Isopropylidene-1-(4-methoxy-benzyl)-piperidineHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 597301486-[4-(3-Isopropyl-piperidin-1-ylmethyl)-phenoxy]-nicotinamideAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9942167Palladium hydroxideKatalysatorHCID 702EthanolLösungsmittel

Versuchsvorschrift

Combine 3-Isopropylidene-1-(4-methoxy-benzyl)-piperidine (227.0 mg, 0.92 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) (104.0 mg, 0.43 mmol), and NaCNBH3 (49.0 mg, 0.78 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 purify by reverse phase chromatography using 5 to 95% 0.001% TFA in CH3CN/H2O to give 37.2 mg (11% yield) of the title compound: 1H NMR (500 MHz, d-MeOH); 0.9 (6H, dd), 0.9-1.1 (1H, m), 1.3-1.6 (3H, m), 1.7-1.9 (3H, m), 1.9-2.0 (1H, m), 2.9 (1H, d) 3.0 (1H, d), 3.5 (2H, dd), 6.9 (1H, d), 7.1 (2H, d), 7.4 (2H, d), 8.2 (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
  8. custompurify by reverse phase chromatography

Quellen und Nachweise

ORD-Eintrag
ord-900ee3801bab49eeba2efb68e5f427f8
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381719B2

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