Sodium hydride → 6-Bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole

HRID 1429524Notes

Reaction equation

HRID 1429524 reaction equation
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].[H-].[Na+].[Br:19][C:20]1[CH:29]=[CH:28][C:23]2[N:24]=[C:25](Cl)[S:26][C:22]=2[CH:21]=1>CN(C=O)C.O>[Br:19][C:20]1[CH:29]=[CH:28][C:23]2[N:24]=[C:25]([O:16][CH:13]3[CH2:14][CH2:15][N:10]([C:7]4[N:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][N:6]=4)[CH2:11][CH2:12]3)[S:26][C:22]=2[CH:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 20498716-Bromo-2-chlorobenzothiazoleHCID 670724781-(5-Propylpyrimidin-2-yl)piperidin-4-ol

Product 1

HCID 674627936-Bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazoleYield 74.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol (160 mg, 0.724 mmol) in DMF (5 mL) was added NaH (36.2 mg, 0.905 mmol) at 0° C. Upon completion of addition, the reaction mixture was allowed to warm to rt and then 6-bromo-2-chlorobenzo[d]thiazole (150 mg, 0.604 mmol) was added. The resulting mixture was heated to 90° C., where it stirred overnight. At the conclusion of this period, the reaction mixture was cooled to rt, diluted with water and then extracted with EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4. The resulting mixture was filtered and concentrated under reduced pressure to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to afford Compound 1C (194 mg, 0.448 mmol, 74.2% yield).

Workup

  1. additionUpon completion of addition
  2. temperatureThe resulting mixture was heated to 90° C.
  3. temperatureAt the conclusion of this period, the reaction mixture was cooled to rt
  4. extractionextracted with EtOAc (3×5 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationThe resulting mixture was filtered
  7. concentrationconcentrated under reduced pressure
  8. customto yield the crude product
  9. customThe crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc)

Sources & evidence

ORD record
ord-f6183abc30f7493fab695737dbc873e3
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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