Finerenone synthesis

Yield:29119-58-2 80%

Reaction Conditions:

Stage #1: 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide in 5,5-dimethyl-1,3-cyclohexadiene; for 8 h;Reflux;
Stage #2: with O,O'-dibenzoyl-D-tartaric acid in lithium hydroxide monohydrate at 30; for 4 h;Reflux;Solvent;

Steps:

1.6; 2.7; 3.7 (6) Synthesis of compound 6:

The solvent xylene was added to the reaction flask, 70 g (0.185 mol) of compound 5 was added, 30 g of catalyst was added, and the mixture was refluxed and stirred for 8 h. Target configuration measured by HPLC: non-target configuration = 84:16, ending transconfiguration. Filtration, the mother liquor was spin-dried to obtain the crude product, 150g of ethanol was added, 50g of water was added, after stirring and dissolving, 58.4g (0.155mol) D-dibenzoyltartaric acid was added, heated to reflux for 3h, cooled to 30°C, stirred for 1h and filtered to obtain The crude product was added to water, 10% sodium phosphate solution was added to adjust pH=7.5, stirred for 0.5 h to precipitate, filtered to obtain the crude product, and recrystallized with 200 g of ethanol to obtain 56 g of feneridone bulk drug with a yield of 80%.

References:

CN114605410,2022,A Location in patent:Paragraph 0046; 0064-0066; 0067; 0076-0077; 0087; 0091-0092