In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 78703-53-4 as follows. Safety of 1,3-Dimethyl-1H-pyrazole-4-carboxylic acid
A mixture of tert-butyl [2-(3-chloro-5-fluorobenzyl)-4-methyl-1,3-thiazol-5-yl]carbamate (500 mg, 1.40 mmol) obtained in Example 145-E), concentrated hydrochloric acid (1 mL) and ethanol (2 mL) was stirred at 50C for 1 hr. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in DMF (3 mL), 1,3-dimethyl-1H-pyrazole-4-carboxylic acid (216 mg, 1.54 mmol), HATU (585 mg, 1.54 mmol) and DIEA (0.12 mL, 0.70 mmol) were added, and the mixture was stirred at 60C for 4 hr. The reaction mixture was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography [eluent: ethyl acetate-methanol (100:0-80:20)]. The obtained solid was crystallized from heptane-ethyl acetate to give the title compound (40 mg) as a pale-brown solid (yield 8%). MS (ESI+): [M+H]+ 379. 1H NMR (300 MHz, CDCl3) delta 2.39 (3H, s), 2.55 (3H, s), 3.88 (3H, s), 4.18 (2H, s), 6.90-7.01 (2H, m), 7.08-7.12 (1H, m), 7.46 (1H, s), 7.81 (1H, s). mp 125-128C
According to the analysis of related databases, 78703-53-4, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2530078; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics