Reference of 1211580-54-9, 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. 1211580-54-9, name is 4-Bromo-2-(difluoromethyl)pyridine. A new synthetic method of this compound is introduced below.
[0208] Step 2: (R)-benzyl 7-(3-(2-(difluoromethyl)pyridin-4-yl)-l-trityl- lH-indazol-5-yl)-6-oxo-2,7-diazaspiro[4.4]nonane-2-carboxylate : To a stirred solution of 4-bromo-2-(difluoromethyl)pyridine (0.520 g, 2.51 mmol) and bis(pinacolato)diboron (1.270 g, 5.02 mmol) in 1,4-dioxane (15 mL), was added potassium acetate (0.740 g, 7.53 mmol). The solution was degassed for 15 mins. [Iota, – bis(diphenylphosphino)ferrocene]dichloropalladium (II) DCM complex (0.102 g, 0.125 mmol) was added. The mixture was degassed for 10 mins followed by refluxing for 3 h. The mixture was cooled to rt and (i?)-benzyl 7-(3-iodo-l -trityl-lH-indazol-5-yl)-6-oxo- 2,7-diazaspiro[4.4]nonane-2-carboxylate (Intermediate 7) (1.523 g, 2.009 mmol) in ethanol: toluene: water (1 : 1 : 1, 15 mL) was added followed by potassium carbonate (1.733 g, 12.56 mmol). The solution was degassed for 20 mins. Tetrakis(triphenylphosphine)palladium(0) (0.145 g, 0.125 mmol) was added. The mixture was degassed for 10 mins followed by refluxing for 3 h. The mixture was cooled to rt and filtered through a Celite pad. To the filtrate was added cold water, and the mixture was extracted with ethyl acetate (3 X 50 mL). The combined organic layers were washed with water (30 mL) and brine (20 mL), dried over sodium sulfate, filtered and concentrated. The crude compound was purified by column chromatography (100-200 silica) using 50% ethyl acetate in hexane as eluent to afford (i?)-benzyl 7-(3-(2- (difluoromethyl)pyridin-4-yl)-l -trityl-lH-indazol-5-yl)-6-oxo-2,7-diazaspiro[4.4]nonane- 2-carboxylate (0.500 g, 0.658 mmol, 33% yield ) as an off white solid . XH NMR (400 MHz, DMSO-de) delta 8.81 (d, J= 5.1Hz, 1H), 8.37 (d, J = 1.5 Hz, 1H), 8.09-8.00 (m, 2H), 7.50 (br d, J = 9.5 Hz, 1H), 7.43-7.27 (m, 14H), 7.20 (dd, J = 1.8, 7.7 Hz, 7H), 6.49 (d, J = 9.2 Hz, 1H), 5.08 (d, J = 3.3 Hz, 2H), 3.91 (br t, J = 6.4 Hz, 2H), 3.66-3.36 (m, 4H), 2.22-2.03 (m, 3H), 1.97 (br d, J = 4.8 Hz, 1H). LCMS : 260.44 [M+H]+.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,1211580-54-9, 4-Bromo-2-(difluoromethyl)pyridine, and friends who are interested can also refer to it.
Reference:
Patent; KALYRA PHARMACEUTICALS, INC.; HUANG, Peter Qinhua; KAHRAMAN, Mehmet; SLEE, Deborah, Helen; BUNKER, Kevin, Duane; HOPKINS, Chad, Daniel; PINCHMAN, Joseph, Robert; ABRAHAM, Sunny; SIT, Rakesh, Kumar; SEVERANCE, Daniel, Lee; (248 pag.)WO2016/161160; (2016); A1;,
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