Sodium hydride → 4-(2-(1-(Quinolin-2-yl)azetidin-3-yloxy)pyridin-3-yl)morpholine

HRID 454937Notes

Reaction equation

HRID 454937 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+].F[C:19]1[C:24]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:23][CH:22]=[CH:21][N:20]=1>CN(C=O)C>[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[C:24]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)=[CH:23][CH:22]=[CH:21][N:20]=2)[CH2:14]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 585476984-(2-Fluoropyridin-3-yl)morpholineHCID 585477211-(Quinolin-2-yl)azetidin-3-ol

Product 1

HCID 585479234-(2-(1-(Quinolin-2-yl)azetidin-3-yloxy)pyridin-3-yl)morpholineYield 91.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(quinolin-2-yl)azetidin-3-ol (see PREPARATION P1.2; 237 mg, 1.186 mmol) in DMF (1.6 mL) was added sodium hydride, 60% in oil (49.4 mg, 1.235 mmol). The reaction mixture was stirred at RT for 15 min and 4-(2-fluoropyridin-3-yl)morpholine (see PREPARATION P17.1; 150 mg, 0.823 mmol) was added. The reaction mixture was heated at 60° C. for 3 hours. The reaction mixture was partitioned between EtOAc and brine. The aqueous layer was back extracted with EtOAc (3×) and the combined organic layers were dried (Na2SO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 80% EtOAc in hexane, to provide 4-(2-(1-(quinolin-2-yl)azetidin-3-yloxy)pyridin-3-yl)morpholine (273 mg, 0.753 mmol, 91% yield) as off-white solid.

Workup

  1. temperatureThe reaction mixture was heated at 60° C. for 3 hours
  2. customThe reaction mixture was partitioned between EtOAc and brine
  3. extractionThe aqueous layer was back extracted with EtOAc (3×)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  7. washeluting with a gradient of 0% to 80% EtOAc in hexane

Sources & evidence

ORD record
ord-942097b4919841398c915c173a194a5e
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

Loading…