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

HRID 228498노트

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HRID 228498 반응식
[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]

참가 물질

8

반응물 5

HCID 5003444Sodium cyanoborohydrideHCID 10129899Acetic acid methanolHCID 471502166-(4-Formylphenoxy)nicotinonitrile2회HCID 597300293-Isopropylidene-1-(4-methoxy-benzyl)-piperidineHCID 178418361HCID 178418361, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 9942167Palladium hydroxide촉매HCID 702Ethanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2a16dac478eb4f97867e0a067e0de242
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07560463B2

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