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

HRID 2207839노트

반응식

HRID 2207839 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c44f10c0f924408bb28317829506fba7
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09376450B2

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