Sodium hydride → 1-(4-(2-(4-(Benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone

HRID 1880139Notes

Reaction equation

HRID 1880139 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.[H-].[Na+].F[C:21]1[C:26]([CH:27]2[CH2:32][CH2:31][N:30]([C:33](=[O:35])[CH3:34])[CH2:29][CH2:28]2)=[CH:25][CH:24]=[CH:23][N:22]=1>CN1CCCC1=O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:21]2[C:26]([CH:27]3[CH2:28][CH2:29][N:30]([C:33](=[O:35])[CH3:34])[CH2:31][CH2:32]3)=[CH:25][CH:24]=[CH:23][N:22]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 585478341-(4-(2-Fluoropyridin-3-yl)piperidin-1-yl)ethanoneHCID 593268134-(Benzo[d]thiazol-2-ylamino)phenol

Product 1

HCID 593268811-(4-(2-(4-(Benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanoneYield 45.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To 4-(benzo[d]thiazol-2-ylamino)phenol (0.327 g, 1.35 mmol) dissolved in N-Methyl-2-pyrrolidinone (3 mL) was added sodium hydride, 60% dispersion in mineral oil (54 mg, 1.4 mmol). After stirring at RT for 10 min, 1-(4-(2-fluoropyridin-3-yl)piperidin-1-yl)ethanone (0.15 g, 0.68 mmol) was added and the reaction mixture was stirred at 140° C. for 16 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and brine. The aqueous layer was back extracted with EtOAc (3×) and the combined organics 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 10% to 100% EtOAc in hexane, followed by trituration with Et2O and hexane to provide 1-(4-(2-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone (0.137 g, 0.308 mmol, 45.7% yield) as off-white solid. MS (ESI, pos. ion) m/z: 445.0 (M+1). IC50 (uM) +++++.

Workup

  1. stirringthe reaction mixture was stirred at 140° C. for 16 h
  2. temperatureAfter cooling to RT
  3. customthe reaction mixture was partitioned between EtOAc and brine
  4. extractionThe aqueous layer was back extracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-4ddb0b97b55147cd88bda6fef6fa67b7
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

Loading…