5334-40-7, These common heterocyclic compound, 5334-40-7, name is 4-Nitro-1H-pyrazole-3-carboxylic acid, its 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 1 L R.B. flask containing 4-nitro-3-pyrazolecarboxylic acid (40 g, 0.255 mol), and t-BuOH (94 g, 122 mL, 1.275 mol, 5 eq.) was added conc. H2SO4 (25 g, 13.5 mL, 0.255 mol); and the reaction mixture was stirred at 100¡ã C. for 2 h. After cooling to rt, the reaction mixture was diluted with EtOAc and water. Then added saturated aq NaHCO3 solution until pH was around 3-4. The aqueous layer was extracted with excess ethyl acetate. The combined ethyl acetate part was dried over any Na2SO4, filtered and distilled off to give 28 g of 1-tert-butyl-4-nitro-1H-pyrazole-3-carboxylic acid as solid.To a vial containing 1-tert-butyl-4-nitro-1H-pyrazole-3-carboxylic acid, (214 mg, 1.0 mmol, 1 eq.) was added PCl5 (240 mg, 1.15 mmol, 1.5 eq.) in chilled toluene (2 mL). The mixture was stirred until all solids dissolved (ca. 5-10 min.). The pre-formed acid chloride solution was then added to 3,3-dimethylpiperazine-2-one (141 mg, 1.10 mmol, 1.1 eq.) and TEA (0.300 mL, 2.15 mmol, 2.15 eq) in DCM (4 mL) and stirred for 45 min. at room temperature. The reaction was quenched with NaHCO3, and the organics extracted with EtOAc, washed with water, and brine. The aqueous portions were back-extracted and the combined organics were dried over MgSO4, filtered and concentrated to an off-white solid, 4-(1-tert-butyl-4-nitro-1H-pyrazole-3-carbonyl)-3,3-dimethylpiperazine-2-one, 310.4 mg.To a rb flask containing 4-(1-tert-butyl-4-nitro-1H-pyrazole-3-carbonyl)-3,3-dimethylpiperazine-2-one (303 mg, 0.937 mmol, 1 eq.) in MeOH (9 mL) was added Pd/C (105 mg, 0.1 eq.). A balloon filled with H2 was attached and the atmosphere of the vessel purged with H2. The contents of the flask were stirred at r.t. overnight. Themixture was filtered through Celite.(R)., eluting with MeOH. The solvent was removed in vacuo to give 4-(4-amino-1-tert-butyl-1H-pyrazole-3-carbonyl)-3,3-dimethylpiperazine-2-one 259.7 mg, as a purple solid.The urea was formed from 4-(4-Amino-1-tert-butyl-1H-pyrazole-3-carbonyl)-3,3-dimethylpiperazine-2-one and 3-(6-isopropylpyridin-3-yl)-4-methylaniline to give 1-(1-tert-butyl-3-(2,2-dimethyl-3-oxopiperazine-1-carbonyl)-1H-pyrazol-4-yl)-3-(3-(6-isopropylpyridin-3-yl)-4-methylphenyl)urea.
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 5334-40-7.