Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 14521-80-3, name is 3-Bromo-1H-pyrazole, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives
1.1 Synthesis of Intermediates P Synthesis of 4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-2, 6-difluorobenzaldehyde (P4) In a 150 mL pressure vessel, a suspension of 3-bromo-1H-pyrazole (8 g, 54.43 mmol) cesium carbonate (53.2 g, 163.29 mmol), and difluoroiodomethane (10% wt. in THF, 200 mL, 106.23 mmol) was heated at 45 C. overnight. The reaction mixture was cooled to room temperature and then filtered through Celite. The filter cake was washed with Et2O (3*150 mL). The filtrate was washed with brine, dried over sodium sulfate and carefully concentrated (20 C. bath, 100 mb vacuum) to give ?17 g of a 1.5:1 ratio of regioisomers and solvent still present. This crude material was combined with 3,5-difluoro-4-formylphenylboronic acid (12.65 g, 68.03 mmol), palladium acetate (0.31 g, 1.381 mmol), butyl di-1-adamantylphosphine (1.171 g, 3.265 mmol) and potassium carbonate (22.80 g, 164.96 mmol) in dioxane (150 mL) and water (50 mL) the mixture was degassed for 10 min with argon, then heated at 100 C. overnight. The reaction mixture was cooled to room temperature, concentrated under reduce pressure, the residue was diluted with EtOAc and washed with brine 2x then dried over Na2SO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (5% to 15% EtOAc/Hex). Mixed fractions were recrystallized (5:1 Hex/EtOAc) and the combined pure product afforded P4. 1H NMR (400 MHz, Chloroform-d) delta 10.35 (d, J=1.0 Hz, 1H), 7.92 (d, J=2.8 Hz, 1H), 7.46 (d, J=9.6 Hz, 2H), 7.24 (t, J=60.5 Hz, 1H), 6.80 (d, J=2.8 Hz, 1H).
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; Gilead Sciences, Inc.; Chin, Elbert; Kato, Darryl; Link, John O.; Shapiro, Nathan; Yang, Zheng-Yu; (81 pag.)US2020/30327; (2020); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics