Synthetic Route of 16034-46-1,Some common heterocyclic compound, 16034-46-1, name is 1-Methyl-1H-pyrazole-5-carboxylic acid, molecular formula is C5H6N2O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a solution of tert-butyl {4-methyl-2-[3-(methylsulfonyl)benzyl]-1,3-thiazol-5-yl}carbamate (300 mg, 0.78 mmol) obtained in Example 233-F) in ethanol (2 mL) was added dropwise concentrated hydrochloric acid (0.600 mL) at room temperature, and the mixture was stirred at 50C for 1 hr. The reaction mixture was cooled to 0C, neutralized with 8N aqueous sodium hydroxide solution, adjusted to pH 10-11 with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in DMA (3 mL), and 1-methyl-1H-pyrazole-5-carboxylic acid (118 mg, 0.94 mmol), HATU (356 g, 0.94 mmol) and DIEA (0.068 mL, 0.39 mmol) were added at room temperature. The reaction mixture was stirred at 60C for 2 hr, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: hexane-ethyl acetate (1:4-0:1)] and basic silica gel column chromatography [eluent: hexane-ethyl acetate (1:9-0:1)], and crystallized from ethyl acetate-hexane to give the title compound (159 mg) as white crystals (yield 52%). MS (ESI+) : [M+H]+ 391. 1H NMR (300 MHz, DMSO-d6) delta 2.31 (3H, s), 3.31 (3H, s), 4.04 (3H, s), 4.37 (2H, s), 7.06 (1H, d, J = 1.9 Hz), 7.53 (1H, d, J = 1.9 Hz), 7.59-7.74 (2H, m), 7.80-7.87 (1H, m), 7.91 (1H, brs), 10.52 (1H, s).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-1H-pyrazole-5-carboxylic acid, its application will become more common.
Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2530078; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics