6-(4-Methylpiperazin-1-yl)picolinaldehyde synthesis

Yield:1216691-10-9 32%

Reaction Conditions:

with potassium carbonate in acetonitrile at 110; for 17 h;Sealed tube;

Steps:

15

Example 15
5,7-Dimethoxy-2-(6-(4-methylpiperazin-1-yl)pyridin-2-yl)quinazolin-4(3M-one Hydrochloride
Preparation of 6-(4-Methylpiperazin-1-yl)picolinaldehyde (3).
A suspension of 6-bromopicolinaldehyde (1.50 g, 8.10 mmol), 1-methylpiperazine (2, 4.04 g, 40.0 mmol), potassium carbonate (4.46 g, 32.0 mmol) and anhydrous CH₃CN (10 mL) was placed in a sealed vessel and the mixture was heated at 110° C. for 17 h.
The mixture was diluted with water (50 mL) and brought to pH 7 using 2 N aq. HCl (15 mL).
The resulting solution was extracted with CH₂Cl₂ (3*50 mL) and the combined extracts were washed with brine (200 mL).
The solution was dried (Na₂SO₄), filtered, concentrated and purified by silica gel chromatography eluting with 0-5% CH₃OH in CH₂Cl₂ to afford the title compound (0.528 g, 32%) as an orange oil: ¹H NMR (500 MHz, CDCl₃) δ 9.84 (s, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.27 (d, J=7.0 Hz, 1H), 6.85 (d, J=7.0 Hz, 1H), 3.67-3.65 (m, 4H), 2.55-2.52 (m, 4H), 2.36 (s, 3H).

References:

US2014/142102,2014,A1 Location in patent:Paragraph 0549; 0550