5-CARBOXY-N-PHENYL-2-1H-PYRIDONE-D5 synthesis

Yield:-

Reaction Conditions:

Stage #1: methyl 6-oxo-1-(phenyl-d5)-1,6-dihydropyridine-3-carboxylatewith water;lithium hydroxide in tetrahydrofuran;methanol at 0 - 20;
Stage #2: with hydrogenchloride in tetrahydrofuran;methanol;water; pH=1;

Steps:

3.2

[143] A round-bottom flask was charged with methyl 6-oxo-1-(phenyl-d₅)-1.6- dihydropyridine-3-carboxylate 25 (1.85 mg, 7.88 mmol), THF (46.6 mL) and MeOH (11.8 mL). The resulting slurry was cooled to 0 oC. A solution of LiOH (562 mg, 23.4 mmol) in water (23.4 mL) was added dropwise via cannula. After stirring for 5 mln the ice bath was removed. The mixture was stirred at rt for 45 min. The mixture was acidified to pH 1 with IN HCl and extracted with EtOAc (3 times). The combined organic layers were washed with brine, dried (Na₂SO₄), filtered and concentrated in vacuo. Purification via column chromatography on an ISCO instrument (0% to 30% MeOH in clichloromethaiie) provided 851 mg of 26. ¹H NMR (DMSOd₆): δ 12.9 (br s, 1 H), 8.1 1 (dd, J = 0,5, 2,4, 1 H), 7,82 (dd, J = 2.7, 9.4, I H), 6.48 (d, J = 9.6, 1 H). MS (M+H): 221.2.

References:

WO2010/65755,2010,A1 Location in patent:Page/Page column 40-41