2(1H)-Pyridinone,6-(hydroxymethyl)-(9CI) synthesis

Yield:352514-21-7 72%

Reaction Conditions:

with dimethylsulfide borane complex in tetrahydrofuran at 20 - 50; for 4 h;Inert atmosphere;

Steps:

247.1

Example 247 2-((6-(((2-amino-5-(2-(difluoromethyl)-6-methylpyridin-4-yl)-6-(4-fluorophenyl)pyrimidin-4- yl)oxy)methyl)pyridin-2-yl)oxy)acetic acid [00544] Step 1 : 6-hydroxymethyl-pyridin-2-ol [00545] To a stirring solution of 6-hydroxy-pyridine-2-carboxylic acid (2.0 g, 14.38 mmol) in THF (10 mL) was added (CfTriS * BH3 (10 M, 7.2 mL, 71.89 mmol) at room temperature under nitrogen. The resulting mixture was stirred at 50 °C overnight, then cooled and quenched with MeOH (30 mL) slowly and carefully. After stirring at 50 °C for 4 h, the mixture was concentrated and purified by column chromatography on silica gel (DCM:MeOH=lO:l) to give 6-hydroxymethyl-pyridin-2-ol (1.3 g, 72%) as a white solid. ES-MS (m/z): [M+l]+ = 126.1.

References:

WO2020/14332,2020,A1 Location in patent:Paragraph 00544-00545