1-Boc-4-bromopyrazole

Step 1: Preparation of tert-butyl 4-bromo-lH-pyrazole-l-carboxylate B [00161] Boc anhydride (2.34 niL, 10.2 mmol) was added to a solution of 4-bromo-lH- pyrazole (1 g, 6.8 mmol), triethylamine (3.3 raL, 23.8 mmol) and 4-dimethylaminopyridine (0.166 g, 1.36 mmol) in acetonitrile (20 mL) at 0 °C and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water and extracted with ethyl acetate (100 niL x 3). The combined organic extract was washed with water (100 mL), brine (100 raL), dried over anhydrous sodium sulfate and evaporated. The crude material was purified by combiflash purifier using 10percent ethyl acetate in hexane to afford the title compound tert-butyl 4- bromo-1 H-pyrazole- 1 -carboxylate (1.65 g, 98percent yield) as a colorless liquid. 4-Bromo-1H-pyrazole, 5.00 g (34.0 mmol), di-tert-butyl dicarbonate, 8.17 g (37.4 mmol), and triethylamine, 7.57 g (74.8 mmol), were added into 50 mL of dichloromethane. The resulting mixture was stirred at room temperature for overnight. The resulting mixture was purified by silica gel column chromatography to give 8.00 g (93percent) of the product as an off-white solid. MS (ESIpos): m/z = 247 [M+H]In the reaction kettle, add 4 - brompyrazole (1.47 kg, 10 µM) and tetrahydrofuran 6 kg, stirring to dissolve, heating to 30 - 40 °C, slow carbon acid di-tert-butyl adds by drops two (2.18 kg, 10 µM), drop the temperature increases slightly, the control temperature of not more than 45 °C. The completion of the dropping, stirring 1 - 2 hours, TLC confirms the completion of the reaction. The reaction liquid under reduced pressure when the distillation is carried out to the does not flow the fluid, adding 1.2 kg normal heptane cooling to 0 °C beating, filtering, drying to obtain N - BOC - 4 - brompyrazole 2.01 kg, yield 92percent, HPLC: 98.3percent.To a mixture of 4-bromo- lH-pyrazole (500 mg, 3.40 mmol) in DCM (10 mL) was added BocGeneral procedure: To a solution of pyrazole 1-5 (1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (for 0.05mol of pyrazole – 50 mL of dichloromethane were user) Di-tert-butyl dicarbonate (1.2 equiv) wereadded at room temperature and left to stir overnight. Dichloromethane was washed with saturatedNaHCO3 solution (1×25 mL – for 50 mL of dichloromethane) then with deionized H2O (1 × 25mL). Organic layer was dried with anhydrous Na2SO4, and evaporated under reduced pressure.

Molecular Weight:247.09
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:246.00039
Monoisotopic Mass:246.00039
Topological Polar Surface Area:44.1
Heavy Atom Count:13
Complexity:203
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes