3-BROMO-1H-PYRAZOLE

A mixture of 3-bromo-N, N-dimethyl-1H-pyrazole-1-sulfonamide obtained in Step B (5.83 g) and trifluoroacetic acid (9.0 mL) was stirred at room temperature for 2 hr. To the reaction mixture was added ethyl acetate, and the mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.92 g). Step B: Preparation of 3-BromopyrazoleStep B: Preparation of 3-BromopyrazoleTo trifluoroacetic acid (70 mE) was slowly added the bromopyrazole product (57.04 g) from Step A. The reactionmixture was stirred at room temperature for 30 minutes and then concentrated at reduced pressure. The residue was takenup in hexane, insoluble solids were filtered off, and the hexanewas evaporated to afford the crude product as an oil. Thecrude product was further purified by chromatography on silica gel using ethyl acetate/dichloromethane (10:90) as elutoent to afford an oil. The oil was taken up in dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with methylene chloride (3x), dried over magnesium sulfate and concentrated to afford the title product as a white solid (25.9 g), m.p. 61-64° C.‘H NMR (CDC13) ö 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H).(1) 6.81 g (0.1 mol) of pyrazole was dissolved in 50.0percent of hydrobromic acid (161.80 g, containing 1.0 mol of hydrogen bromide).Under stirring, the temperature is controlled at 5-15° C., and a 25.0percent solution of potassium dichromate 47.07 g is added dropwise.After completion of the dropwise addition, the reaction temperature was controlled at 5-15° C. to allow the reaction system to undergo a bromination reaction. During the reaction, samples were taken at regular intervals and detected by high performance liquid chromatography.When it was detected that the mass of 3-bromopyrazole in the reaction system accounted for 93.0percent of the total mass of organic matter in the reaction system, 4.31 g (0.06 mol) of ferrous oxide was added to terminate the reaction to obtain a feed liquid containing 3-bromopyrazole; (2) Add 73.5 g of chlorobenzene to the feed solution, stir and extract for 2 hours, let stand for 1 hour, take the organic phase and allow it to cool down to -15°C to -5°C, The solids were analyzed by elution from the organic phase. The resulting 12.20 g of solid was 3-bromopyrazole. The yield was calculated to be 83percent. After the determination, the main content was 98.5percent.Part C. A 100 mL flask with a stir bar was charged with iodo-morpholine intermediate (1.2 g, 2.0 mmol) and 10 mL of methylene chloride before the dropwise syringe addition of 1 mL TFA. The system was flushed with N2 while the reaction stirred overnight at rt. The solution was diluted with methylene chloride and saturated sodium bicarbonate before transfer to an addition funnel. The aqueous phase was separated and extracted three times with methylene chloride. The organics were combined and washed with brine before drying over magnesium sulfate. The solution was filtered and solvent was removed by rotary evaporation to yield the 3-bromopyrazole as an orange solid.The crude reaction product was purified by flash chromatography to produce pure 3-bromopyrazole (560 mg, 1.1 mmol) in 53% yield.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 Intermediate 4.1 .A (0304) 6-[(3-bromo-1 FI-pyrazol-1 -yl)methyl1-5-methyl-[1 .2.51oxadiazolo[3, 4-blpyridin-7-amineStep 1: To To a solution of To a solution of A mixture of To a solution of

3-Bromopyrazole is a useful intermediate for the synthesis of Rynaxypyr (C325380); an insecticidal o-aminodiamine with a potent and selective rianodine receptor activator.

Molecular Weight:146.97
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:145.94796
Monoisotopic Mass:145.94796
Topological Polar Surface Area:28.7
Heavy Atom Count:6
Complexity:48.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes