Reference of 22236-08-4, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 22236-08-4 as follows.
Intermediate.11 rac-Allyl [l -{N’-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl} -3-(3,4-dichlorophenyl)-4,5- dihydro- l//-pyrazol-4-yl]carbamate To a stirred solution of m-difluoromethoxy aniline, 8.20 ml. (65.5 mmol) in anhydrous tetrahydrofuran (100 mL) at -78 C was added n -butyl lithium, 33.0 mL (65.5 mmol, 2 M in hexane) dropwise, while maintaining the reaction temperature below -65 C during the addition. The reaction mixture was stirred for 1 hour at -78 C before rac-phenyl 4-{[(ailyioxy)carbonyl]amino}-N-cyano-3-(3,4- dichlorophenyl)-4,5-dihydro- 1 H-pyrazole- 1 -carboximidate (intermediate 9), 10.0 g (21.8 mmol) in anhydrous tetrahydrofuran (600 mL) was added dropwise maintaining the reaction temperature below -65 C. The reaction mixture was stirred for 2 hours at -78 C before slowly pouring over saturated ammonium chloride solution (700 mL). The crude product was extracted into ethyl acetate (700 mL) and the organic layers were combined and washed with brine solution (350 mL). The collected organic phase was dried over magnesium sulfate, filtered and the solvent evaporated to yield an off-white crude solid. The crude solid was precipitated from a minimum volume of ethyl acetate, filtered, and washed with diethyl ether to yield rac-allyl [ 1 – {N’-cyano-N- [3 – (difluoromethoxy)phenyi]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-lH-pyrazoi-4- yl] carbamate, 7.6 g (67%) as a white solid. NM R (400 MHz, DMSO-d6): delta [ppm] = 4.08 (dd, 1H), 4.36-4.53 (m, 3H), 5.11 (dd, 1H), 5.17 (dd, 1H), 5.50-5.59 (m, 1H), 5.77-5.90 (m, 1H), 6.99 (dd, 1H), 7.16 (t, 1H), 7.21 (t, 1H), 7.23 (dd, 1H), 7.39 (t, 1H), 7.73-7.81 (m, 2H), 8.15 (d, 1H), 8.17 (d, 1H), 9.79 (br s, 1H). I MS (method 3): Rt = 1.78 min MS (ESI): [M + Hf = 523.2
According to the analysis of related databases, 22236-08-4, the application of this compound in the production field has become more and more popular.
Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; STELLFELD, Timo; MOWAT, Jeffrey Stuart; STRESEMANN, Carlo; HILLIG, Roman; KOeHR, Silke; STOeCKIGT, Detlef; WEISKE, Joerg; HARTUNG, Ingo; BARAK, Naomi; CHRIST, Clara; TER LAAK, Antonius; BADOCK, Volker; CRAMPTON, Rosemary Helen; STEFANUTI, Ian; (194 pag.)WO2016/166186; (2016); A1;,
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