2-(1-methylpiperazin-2-yl)ethanol synthesis

Yield:-

Reaction Conditions:

Stage #1: methyl 2-(1-methyl-3-oxopiperazin-2-yl)acetatewith lithium aluminium tetrahydride in tetrahydrofuran; for 2 h;Heating / reflux;
Stage #2: with sodium hydroxide;water in tetrahydrofuran; pH=12;

Steps:

U.U-24

Example U -24; 2-(2,6-difluorophenyl)-5-(4-(2-(2-hydroxyethyl)-1-methylpiperazine-4- carbonyl)phenylamino)oxazole-4-carboxamide; 2-(1-methylpiperazin-2-yl)ethanol was prepared by dissolving methyl 2-(1-methyl-3- oxopiperazin-2-yl)acetate (0.50Og₁ 2.50mmol, prepared according to Abelman et al., Tetrahedron Letters, 44 (2003), 1823-1826) in THF (10ml) followed by addition of LiAIH₄ (2M in THF, 3.12ml, 6.24mmol). The resulting solution was refluxed for 2h, concentrated in vacuo, basified to pH12 with 1M NaOH solution and filtered through a celite pad. The filtrate was purified by SPE using a TsOH cartridge to give 2-(1-methylpiperazin-2- yl)ethanol as a golden oil (0.125g, 0.87mmol). 2-(2,6-difluorophenyl)-5-(4-(2-(2- hydroxyethyO-i-methylpiperazine^-carbonylJphenylaminoJoxazole^-carboxamide was then prepared using the method described in example U-12. ¹H NMR (CD₃OD) δ 1.35- 1.40 (1 H, m), 1.92-2.05 (1 H, m), 2.10-2.20 (2H₁ m), 2.36 (3H, S)₁ 2.30-2.38 (1 H, m), 2.85-2.95 (2H, m), 3.25-3.35 (2H₁ m), 3.55-3.65 (2H₁ br. s), 7.15-7.25 (2H, m), 7.42-7.48 (2H₁ m), 7.50-7.60 (3H₁ m) LCMS (2) 1.96min; m/z (ES+) 486.

References:

WO2008/139161,2008,A1 Location in patent:Page/Page column 220-221