6-(4-METHYLPIPERAZIN-1-YL)-2-BROMOPYRIDINE synthesis

Yield:153976-27-3 88%

Reaction Conditions:

with potassium phosphate in 1,4-dioxane at 105; for 16 h;Inert atmosphere;

Steps:

Preparation of 1-(6-Bromo-pyridin-2-yl)-4-methyl-piperazine, 6C (X=N; Y=C; X₁=N-CH₃; n=2, Scheme 1)

In a 100 mL round bottom flask 2,6-dibromopyridine (1 g, 4.22 mmol), N-methylpiperazine (464 mg, 4.64 mmol), anhydrous potassium phosphate (0.896 g, 4.22 mmol) were taken in dry 1,4-Dioxane (60 ml) and reaction was heated at 105° C. under inert conditions for 16 h, cooled to room temp, solvents were removed under vacuum, residue was diluted with water, partitioned in DCM: Water, washed with brine, the organic layer was dried over sodium sulfate, filtered and concentrated under vacuum to give crude product, purified by flash chromatography using silica gel column (8:2 Hex/EtOAc; 80 g) to give pure 1-(6-Bromo-pyridin-2-yl)-4-methyl-piperazine 6C (0.90 g, 88%). C10H14BrN3 (256.14). ES-MS (m/z), found: 257.04 (M+H). ¹H NMR (400 MHz, CDCl₃) δ 7.25 (dd, J=8.4, 7.5 Hz, 1H), 6.72 (d, J=7.4 Hz, 1H), 6.49 (d, J=8.4 Hz, 1H), 3.67-3.45 (m, 4H), 2.57-2.41 (m, 4H), 2.31 (d, J=2.7 Hz, 3H).

References:

US2018/312497,2018,A1 Location in patent:Paragraph 0065; 0137