5-(1-Hydroxyethyl)-1H-pyrazole-3-carboxylic acid synthesis

Yield:1297538-32-9 73.2%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine;N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate in tetrahydrofuran at -10; for 2 h;Inert atmosphere;

Steps:

8-10 Example 8 Synthesis of the compound Darolutamide represented by formula I

At -10°C, compound 6 (2.61g, 10mmol), compound 7 (1.56g, 10mmol), DIPEA (2.58g, 20mmol) and HATU (3.8g, 10mmol) were added to THF (25mL) and kept at- The reaction was stirred at 10°C for 2h. The reaction solution was quenched by adding saturated NaHCO3 solution (20mL), extracted with EA (25mL), the organic phase was washed with saturated NaHCO3 solution, dried and concentrated, and then column chromatography (column chromatography using dichloromethane and methanol with a volume ratio of 20:1 (Eluted with mixed solvents) to obtain the compound of formula I Darolutamide, the yield is 2.92 g, the yield is 73.2%, and the HPLC purity is 99.3%.

References:

CN111116476,2020,A Location in patent:Paragraph 0059-0065