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

HRID 1429571Notes

Reaction equation

HRID 1429571 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[S:8][C:4]=2[CH:3]=1.Cl[C:19]1[N:24]=[CH:23][C:22]([CH2:25][CH2:26][CH3:27])=[CH:21][N:20]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:11][CH2:12][N:13]([C:19]4[N:24]=[CH:23][C:22]([CH2:25][CH2:26][CH3:27])=[CH:21][N:20]=4)[CH2:14][CH2:15]3)[S:8][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27357842-Chloro-5-propylpyrimidineHCID 674668246-Bromo-2-(piperidin-4-yloxy)-benzothiazole

Product 1

HCID 674627936-Bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazoleYield 86.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-bromo-2-(piperidin-4-yloxy)benzo[d]thiazole (10 g, 31.9 mmol) and 2-chloro-5-propylpyrimidine (7.5 g, 47.9 mmol) in DMF (150 mL) was added potassium carbonate (17.65 g, 128 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was cooled to rt, diluted with water (300 mL) and extracted with EtOAc (3×150 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The crude product was purified by chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to afford 6-bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole (11.9 g, 27.5 mmol, 86% yield) as a white solid. 1H NMR (500 MHz, chloroform-d) δ ppm 8.17 (2H, s), 7.77 (1H, d, J=1.9 Hz), 7.52-7.55 (1H, m), 7.45-7.49 (1H, m), 5.41-5.49 (1H, m), 4.23 (2H, ddd, J=13.4, 6.8, 4.0 Hz), 3.62-3.74 (2H, m), 2.42 (2H, t, J=7.6 Hz), 2.14-2.23 (2H, m), 1.89-1.99 (2H, m), 1.56-1.63 (2H, m), 0.95 (3H, t, J=7.4 Hz).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with EtOAc (3×150 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc)

Sources & evidence

ORD record
ord-02743dfda5dc49859d9b6a2fa9c076ef
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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