1-(5-BROMOPYRIMIDIN-2-YL)-4-PIPERIDINOL synthesis

Yield:887425-47-0 99%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in acetonitrile; for 15 h;Heating / reflux;

Steps:

5.1

Step 1 : 1-(5-Bromo-2-pyrimidinyl)-4-piperidinol (16)A round-bottomed flask was charged, under N₂, with 4-hydroxypiperidine (1.93 g, 10 mmol), diisopropylethylamine (5.22 ml_, 30 mmol), 5-bromo-2-chloropyrimidine (1.01 g, 10 mmol), and acetonitrile (50 ml_). The mixture was refluxed for 15 h and then concentrated under reduced pressure. The crude product was redissolved in CH₂CI₂ (150 ml), washed with H₂O (2 x 20 ml_), brine (1 x 20 ml_), dried over Na₂SO₄, and filtered. The filtrate was concentrated under reduced pressure and the crude material was purified by flash SiO₂ column chromatography to afford 2.55 g (99%) of the title compound 16 as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.34 (s, 2 H), 4.73 (d, J = 4.0 Hz, 1 H), 4.17 - 4.12 (m, 2 H), 3.74 - 3.68 (m, 1 H), 3.28 - 3.22 (m, 2 H), 1.76 - 1.70 (m, 2 H), 1.33 - 1.25 (m, 2 H); LCMS (ESI): m/z 260 (M + H)⁺.

References:

WO2008/8895,2008,A1 Location in patent:Page/Page column 70