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

Temperature

100 °C

To a solution of 6-bromo-2-(piperidin-4-yloxy)benzo[d]thiazole (190 mg, 0.607 mmol) and 2-chloro-5-propylpyrimidine (114 mg, 0.728 mmol) in DMF (4 mL) was added K2CO3 (252 mg, 1.820 mmol). Upon completion of addition, the reaction mixture was heated to 100° C., where it stirred overnight. At the conclusion of this period, the reaction mixture was cooled to rt, diluted with water (10 mL) and then extracted with EtOAc (3×10 mL). The combined organic layers were dried (Na2SO4), filtered, and then concentrated to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 30% EtOAc) to afford Compound 1C as a white solid (131 mg, 0.302 mmol, 50% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 8.17 (s, 2H), 7.77 (d, J=1.9 Hz, 1H), 7.51-7.56 (m, 1H), 7.44-7.49 (m, 1H), 5.40-5.49 (m, J=7.9, 7.9, 4.0, 3.9 Hz, 1H), 4.23 (ddd, J=13.4, 6.8, 4.0 Hz, 2H), 3.63-3.73 (m, 2H), 2.42 (t, J=7.6 Hz, 2H), 2.14-2.22 (m, 2H), 1.89-1.99 (m, 2H), 1.56-1.64 (m, 2H), 0.95 (t, J=7.4 Hz, 3H).

1. additionUpon completion of addition
2. temperatureAt the conclusion of this period, the reaction mixture was cooled to rt
3. extractionextracted with EtOAc (3×10 mL)
4. dry with materialThe combined organic layers were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield the crude product
8. customThe crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 30% EtOAc)

ORD record

ord-73b65d31a82044c2bc7b15fc5db34472

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940716B2