Ammonium Chloride → 1-(1-(3-((1-(Quinolin-2-YL)azetidin-3-YL)oxy)pyridazin-4-YL)piperidin-4-YL)ethanol

HRID 2207839Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2207839
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:14][CH:13]([O:15][C:16]2[N:17]=[N:18][CH:19]=[CH:20][C:21]=2[N:22]2[CH2:27][CH2:26][CH:25]([C:28](=[O:30])[CH3:29])[CH2:24][CH2:23]2)[CH2:12]1.[BH4-].[BH4-].[BH4-].[BH4-].[Na+].[Na+].[Na+].[Na+].[Cl-].[NH4+]>CO>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:12][CH:13]([O:15][C:16]2[N:17]=[N:18][CH:19]=[CH:20][C:21]=2[N:22]2[CH2:23][CH2:24][CH:25]([CH:28]([OH:30])[CH3:29])[CH2:26][CH2:27]2)[CH2:14]1

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 585480461-(1-(3-((1-(Quinolin-2-yl)azetidin-3-yl)oxy)pyridazin-4-yl)piperidin-4-yl)ethanoneHCID 131720822Sodium tetraborohydride

Produkt 1

HCID 585478571-(1-(3-((1-(Quinolin-2-YL)azetidin-3-YL)oxy)pyridazin-4-YL)piperidin-4-YL)ethanolAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

1-(1-(3-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyridazin-4-yl)piperidin-4-yl)ethanone (100 mg, 0.25 mmol) was dissolved in 10 ml of methanol. This solution was cooled down to 0° C. using an ice bath and sodium tetraborohydride (19 mg, 0.50 mmol) was added by portions. The reaction mixture was stirred for 4 hours at ambient temperature, and then saturated aqueous solution of ammonium chloride (5 mL) was added. The methanol was evaporated off under reduced pressure then the reaction mixture was taken up in ethyl acetate. The organic layer was separated from the aqueous layer. The aqueous layer was back extracted one more time with ethyl acetate. The organic layers were combined and dried over magnesium sulfate, followed by concentration under reduced pressure. The residue was purified by column chromatography on silica gel to give (racemic mixture) 1-(1-(3-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyridazin-4-yl)piperidin-4-yl)ethanol (76 mg, 0.19 mmol, 75% yield). ESI-MS (M+1): 406 calc. for C23H27N5O2 405. PDE10 IC50 (uM): 0.0767. 1H NMR (CD3OD, 400 MHz) δ (ppm): δ (ppm) 8.40 (m, 1H); 8.14-8.10 (d, J=8.8 Hz, 1H); 7.97 (d, J=8.8 Hz, 1H); 7.64-7.58 (m, 2H); 7.51-7.46 (m, 1H); 7.20-7.16 (m, 1H); 6.80-6.79 (m, 1H); 6.62 (d, J=9.2 Hz, 1H); 5.62-5.59 (m, 1H); 4.61-4.57 (m, 2H); 4.18-4.15 (m, 2H); 3.96-3.93 (m, 2H); 3.48-3.43 (m, 1H); 2.73-2.67 (m, 2H); 1.91-1.88 (m, 1H); 1.66-1.64 (m, 1H); 1.42-1.34 (m, 3H); 1.11-1.10 (d, 3H).

Aufarbeitung

  1. customThe methanol was evaporated off under reduced pressure
  2. customThe organic layer was separated from the aqueous layer
  3. extractionThe aqueous layer was back extracted one more time with ethyl acetate
  4. dry with materialdried over magnesium sulfate
  5. concentrationfollowed by concentration under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-c44f10c0f924408bb28317829506fba7
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09376450B2

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