Category: 1211580-54-9

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;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 1211580-54-9 ,Some common heterocyclic compound, 1211580-54-9, molecular formula is C6H4BrF2N, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To a solution of 4-bromo-2-(difluoromethyl)pyridine (2.5 g, 12.02 mmol), ethynyltrimethylsilane (2.5 mL, 18.03 mmol) and triethylamine (8.4 mL, 60.10 mmol) in DMF (30.0 mL) was degassed by bubbling with argon for 30 min treated with Pd(PPh3)2Cl2 (0.42 g, 0.60 mmol) with continued argon bubbling, treated Cul (0.23 g, 1.20 mmol), warmed to 65C overnight. Reaction mixture was cooled to room temperature and partitioned between 1M HC1 and EtOAc. The organic layer was washed with brine, dried over Na2S04, filtered and concentrated. The suspension was concentrated to dryness and the resulting crude product was purified by Teledyne-Isco flash system by using Hexane/EtOAc, 0 to 5% of hexane in ethyl acetate to provide compound 17 as light yellow liquid ( 1.85 g, 69% yield). lH NMR (400 MHz, DMSO-d6) delta (ppm): 8.70 (d, 1H), 7.69 (s, 1H), 7.61 (d, 1H), 7.09-6.81 (m, 1H), 0.26 (s, 9H); MS (ESI): Calcd. for Cl lH13F2NSi: 225, found 226 (M+H)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1211580-54-9, its application will become more common.

Reference:
Patent; NANTBIO, INC.; TAO, Chunlin; POLAT, Tulay; YU, Chengzhi; (65 pag.)WO2019/5297; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 1211580-54-9 ,Some common heterocyclic compound, 1211580-54-9, molecular formula is C6H4BrF2N, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To a mixture of 4-bromo-2-(difluoromethyl)pyridine (compound I-3a, 416 mg, 2.0 mmol) and diphenylmethanimine (725 mg, 4.0 mmol) in toluene (15 mL) were added Pd2(dba)3 (92 mg, 0.1 mmol), i-BuXPhos (85 mg, 0.2 mmol) and NaOi-Bu (577 mg, 6 mmol). The reaction mixture was heated at 100 C for 2 hours. The reaction mixture was cooled down, diluted with EtOAc (30 mL), and washed with water. The organic layer was separated and concentrated to give crude compound I-3b (617 mg). MS obsd. (ESI+) [(M+H)+]: 309. Compound I-3b (617 mg, 2 mmol) was dissolved in THF (10 mL) and hydrochloride acid (2 mL, 12 M). The resulting mixture was stirred at room temperature for 2 hours, and then concentrated. The residue was dissolved in DCM (5 mL), followed by addition of DIPEA (1 mL, 5.8 mmol) and phenyl carbonochloridate (251 mu, 2.0 mmol) at 0 C. The resulting mixture was stirred at room temperature for 2 hours, and then poured into water (20 mL), and extracted with EtOAc (20 mL) twice. The organic layers were combined and concentrated, and the residue was purified by column chromatography (eluting with 0 ~20 EtOAc in petroleum ether) to afford intermediate 1-3 (264 mg) as a white solid. MS obsd. (ESI+) [(M+H)+]: 265

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1211580-54-9, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; HAN, Xingchun; LIN, Xianfeng; SHEN, Hong; HU, Taishan; ZHANG, Zhisen; (96 pag.)WO2018/11163; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem