Sodium hydride → 1-(1-(3-((1-(Quinolin-2-YL)azetidin-3-YL)oxy)pyridazin-4-YL)piperidin-4-YL)ethanol

HRID 454941Notes

Reaction equation

HRID 454941 reaction equation
[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]([OH:15])[CH2:12]1.[H-].[Na+].Cl[C:19]1[N:20]=[N:21][C:22](Cl)=[CH:23][C:24]=1[N:25]1[CH2:30][CH2:29][CH:28]([C:31](=[O:33])[CH3:32])[CH2:27][CH2:26]1>CN(C=O)C.O>[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:19]2[N:20]=[N:21][CH:22]=[CH:23][C:24]=2[N:25]2[CH2:30][CH2:29][CH:28]([CH:31]([OH:33])[CH3:32])[CH2:27][CH2:26]2)[CH2:14]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 585477211-(Quinolin-2-yl)azetidin-3-olHCID 585479571-(1-(3,6-Dichloropyridazin-4-yl)piperidin-4-yl)ethanone

Product 1

HCID 585478571-(1-(3-((1-(Quinolin-2-YL)azetidin-3-YL)oxy)pyridazin-4-YL)piperidin-4-YL)ethanolYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(quinolin-2-yl)azetidin-3-ol (see PREPARATION P1.2, step 1; 0.78 g, 3.8 mmol) in DMF (20 mL) at room temperature was added sodium hydride (60% wt in mineral oil) (0.18 g, 7.6 mmol). The mixture was stirred at room temperature for 10 min and then 1-(1-(3,6-dichloropyridazin-4-yl)piperidin-4-yl)ethanone (1.0 g, 3.8 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour and then diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) to give the title product (1.1 g, 2.6 mmol, 70% yield) as white solid. ESI-MS (M+1): 438 calc. for C24H25ClN4O2 437.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 hour
  2. extractionextracted with EtOAc (2×30 mL)
  3. washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-42678a2c0f7a49c4ac7765854eac9ab8
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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