2,2-Dimethyl-5-(pyridin-3-ylaminomethylene)-[1,3]dioxane-4,6-dione synthesis

Yield:25063-68-7 90%

Reaction Conditions:

Stage #1: cycl-isopropylidene malonate;orthoformic acid triethyl ester at 90; for 1.5 h;Large scale;
Stage #2: pyridin-3-ylamine in ethanol at 60 - 70; for 0.666667 h;Large scale;

Steps:

2,2-dimethyl-5-((pyridin-3-ylamino)methylene)-1,3-dioxane-4,6-dione (112)

(0527) A mixture of triethyl orthoformate (1.665 mL, 10.0 mmol) and 2,2-dimethyl-1,3-dioxane-4,6-dione (865 mg, 6.0 mmol) was heated at 90°C for 1.5 h and then cooled to 70°C. 3-amino- pyridine 15 (471 mg, 5.0 mol) was slowly added over 10 min with an EtOH (20 mL) rinse while maintaining the reaction temperature between 60 and 70°C. The reaction was then heated for an additional 30 min and allowed to cool to RT. The precipitate was filtered, washed with EtOH (20 mL), and dried to yield compound as a light-yellow solid (1118mg, 90%). 1H NMR (400 MHz, chloroform-i δ 1 1.25 (d, J= 14.2 Hz, 1H), 8.66 - 8.59 (m, 2H), 8.55 (dd, J= 4.8, 1.4 Hz, 1H), 7.61 (ddd, J= 8.3, 2.8, 1.4 Hz, 1H), 7.41 (dd, J = 8.3, 4.7 Hz, 1H), 1.77 (s, 6H).

References:

WO2019/89648,2019,A1 Location in patent:Page/Page column 67