Sodium hydride → HCID 178522110, compound

HRID 1846803Notes

Reaction equation

HRID 1846803 reaction equation
[H-].[Na+].[OH:3][C@H:4]1[CH2:7][C@H:6]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[O:9])[CH2:5]1.F[C:18]1[C:23]([CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:22][CH:21]=[CH:20][N:19]=1>CN(C=O)C.CCOC(C)=O>[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[NH:10][C:8]([C@H:6]1[CH2:7][C@H:4]([O:3][C:18]2[C:23]([CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:22][CH:21]=[CH:20][N:19]=2)[CH2:5]1)=[O:9]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 593271552-Fluoro-3-(tetrahydro-2H-pyran-4-yl)pyridineHCID 178522109HCID 178522109, compound

Product 1

HCID 178522110HCID 178522110, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (0.073 g, 1.8 mmol, 60% dispersion in mineral oil) was added to a stirred solution of trans-3-hydroxy-N-(pyridin-2-yl)cyclobutanecarboxamide (0.18 g, 0.92 mmol) in DMF (3.5 mL) under an argon atmosphere. The mixture was stirred at RT for 1 h. 2-fluoro-3-(tetrahydro-2H-pyran-4-yl)pyridine (0.17 g, 0.92 mmol) was added, and the reaction mixture was stirred at 60° C. for 18 h. The reaction mixture was diluted with EtOAc and washed with saturated ammonium chloride. The organic layer was separated, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The resulting crude product was purified via silica gel chromatography to give trans-N-(pyridin-2-yl)-3-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)cyclobutanecarboxamide as a white solid. [M+1]=354.0. IC50 (uM): 3.066.

Workup

  1. stirringthe reaction mixture was stirred at 60° C. for 18 h
  2. washwashed with saturated ammonium chloride
  3. customThe organic layer was separated
  4. washwashed with saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting crude product was purified via silica gel chromatography

Sources & evidence

ORD record
ord-bfca220978b741a08015b9a37ad66da6
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

Loading…