Potassium Carbonate → 6-Bromo-2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazole

HRID 1429556Notes

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.Br[C:19]1[S:20][C:21]([CH3:24])=[N:22][N:23]=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[S:20][C:21]([CH3:24])=[N:22][N:23]=4)[CH2:14][CH2:15]3)[S:8][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 6-bromo-2-(piperidin-4-yloxy)benzo[d]thiazole (Compound 1B, 600 mg, 1.916 mmol) and 2-bromo-5-methyl-1,3,4-thiadiazole (480 mg, 2.68 mmol) in DMF (15 mL) was added potassium carbonate (794 mg, 5.75 mmol). The reaction mixture was stirred at 110° C. overnight. The reaction mixture was cooled to rt, diluted with water (20 mL), and extracted with EtOAc (3×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 100% EtOAc) to afford 6-bromo-2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazole (455 mg, 1.106 mmol, 58% yield) as a yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 7.78 (1H, d, J=1.9 Hz), 7.50-7.56 (1H, m), 7.45-7.50 (1H, m), 5.40-5.52 (1H, m), 3.77-3.88 (2H, m), 3.54-3.66 (2H, m), 2.61 (3H, s), 2.19-2.29 (2H, m), 2.07-2.17 (2H, m). LCMS (m/z)=412 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to rt
extractionextracted with EtOAc (3×10 mL)
dry with materialThe combined organic layers were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 100% EtOAc)

Sources & evidence

ORD record: ord-854a648c37a34220a6d131a0ab1bcafd
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940716B2

Reaction notes

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