Month: November 2020

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, This compound has unique chemical properties. The synthetic route is as follows., 13526-66-4

mixture of 2.0 g (16.8 mmol) furo[3,2-b]pyridine and anhydrous THF (100 mL) was cooled to -78 C. 10.1 mL (25.2 mmol) of a 1 .6 M solution of n-butyllithium in hexane was added and the resulting mixture stirred for 1 h at -78 C. 6.8 mL (25.2 mmol) of tributyltin chloride was added at -78 C. The cooling bath was removed and the reaction was stirred at room temperature over night. Methanol was carefully added and the solvent evaporated. The obtained residue was purified by flash chromatography to yield 7.4 g of crude product of the corresponding 2-stannylbenzofurane, which was used without further purification. In an inert atmosphere, 3.0 g (12.9 mmol) of 3-bromo-6-chloro-imidazo[1 ,2-b]- pyridazine, 6.85 g (16.8 mmol) of the crude 2-stannylfuro[3,2-b]pyridine, 246 mg (1 .29 mmol) copper (I) iodide and 453 mg (0.645 mmol) bis(triphenylphosphine) palladium(ll)chloride in 100 mL of THF was stirred over night at 85 C in a sealed pressure tube. The solvent was evaporated, the obtained solid was digested in dichloromethane/methanol and filtered off. The solid was washed with methanol and hexane to give 2 g of the title compound as solid material. 1H-NMR (300 MHz, DMSO-de), delta [ppm]= 7.35-7.45 (1 H), 7.57-7.64 (1 H), 7.65-7.70 (1 H), 8.08-8.15 (1 H), 8.40-8.47 (1 H), 8.47-8.52 (1 H), 8.54-8.62 (1 H). LCMS (Method 3): Rt = 0.91 min; MS (ESIpos) m/z = 271 [M+H]+.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ZORN, Ludwig; EIS, Knut; SCHULZE, Volker; SUeLZLE, Detlev; PUeHLER, Florian; LIENAU, Philip; BOeMER, Ulf; PETERSEN, Kirstin; HAeGEBARTH, Andrea; WO2014/118135; (2014); A1;,
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126764-17-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 126764-17-8 name is 1-Chloro-6,6-dimethylhept-2-en-4-yne, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

N-Methyl-l-naplithylmethylamine (100 g) was dissolved in water (250 ml). Sodium hydroxide (41.50 g) was dissolved in water (120 ml) and this aqueous sodium hydroxide solution was added to N-Met^yl-I-napththyliriethylatnine solution at 20-400C. The reaction mass was heated to 90-950C and l-chloro-6,6- dimethyl-hept-2-ene-4-yne (96 g, crude viscous oily mass having chromatographic purity by GC 92.40%, as obtained in Step A) was added at 90- 100C. The reaction mass was stirred at 90-1000C for 2 hrs and then cooled to room temperature. Methylene chloride (400 ml) was added and organic layer separated. The methylene chloride extract was washed with water (150 ml). The washed methylene chloride solution was stirred with 300 ml dilute hydrochloric acid at room temperature for 1 h. The methylene chloride layer was washed with water (100 ml) and treated with carbon (4 g) at room temperature. The methylene chloride was stripped to get a residue. The residue was refluxed for 30 min with ethyl acetate (600 ml). The product slurry was cooled to room temperature and stirred for 30 min. Product was filtered and washed with preheated ethyl acetate (160 ml, 40-450C). Product was dried at 55-600C under reduced pressure for 4 h to yield 104 g of Terbinafne hydrochloride, containing 1087 ppm of impurity of Formula IV.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Chloro-6,6-dimethylhept-2-en-4-yne, and friends who are interested can also refer to it.

Reference:
Patent; AUROBINDO PHARMA LTD; WO2007/52089; (2007); A1;,
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Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 96558-78-0, name is 3-Bromo-5-chlorophenylamine, This compound has unique chemical properties. The synthetic route is as follows., 96558-78-0

To a solution of 3-bromo-5-chloro-aniline (0.2 g, 968.7 pmol, 1 eq), 2-isopropenyl- 4,4,5,5-tetramethyl-l,3,2-dioxaborolane (195.3 mg, 1.2 mmol, 1.2 eq) and K2CO3 (267.8 mg, 1.9 mmol, 2 eq) in 2 mL of dioxane and 0.2 mL of H2O was added Pd(dppf)Ch (70.9 mg, 96.9 pmol, 0.1 eq) and purged with N2 for 3 times. The mixture was stirred at 100C for 12 hours. The reaction mixture was partitioned between 3 mL of water and 5 mL of ethyl acetate. The organic phase was separated, washed twice with 2 mL of brine, dried over Na2SC>4, filtered and concentrated under reduced pressure to give a residue, which was purified by prep-TLC (S1O2, eluting with Petroleum ether : Ethyl acetate = 5: 1) to give 83 mg of compound 2 (495.1 pmol, 51.1 % yield) as a green oil

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; AQUINNAH PHARMACEUTICALS, INC.; VACCA, Joseph, P.; WAGER, Travis, T.; (383 pag.)WO2020/117877; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

363-51-9, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 363-51-9, name is 2-Chloro-6-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows.

Step B: Preparation of l-chloro-3-fluoro-2-isothiocyanatobenzene A solution of 2-chloro-6-fluorobenzenamine (29.2 g, 0.20 mol) in chlorobenzene (200 mL) was treated with N,N-dimethylformamide (0.10 mL) and then thiophosgene (27.6 g, 0.24 mol) dropwise at room temperature. The reaction mixture was heated to reflux for 2.5 hours and allowed to stir at room temperature for 18 hours. The suspension was filtered through a pad of silica gel and washed with hexane. The filtrate was concentrated under vacuum to give a crude oil which was chromatographed on silica gel with hexane to yield the title compound as a light yellow oil (31.5 g). H NMR (CDC13) delta 7.23-7.19 (m, 1H), 7.18-7.13 (td, 1H), 7.10-7.04 (m, 1H).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; OBERHOLZER, Matthew, Richard; WO2014/189753; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

108-70-3, The chemical industry reduces the impact on the environment during synthesis 108-70-3, name is 1,3,5-Trichlorobenzene, I believe this compound will play a more active role in future production and life.

Example 97.2-(4,6-Dichloro- 1 -methyl- 1 H-indazol-3 -yl)-5H-pyrrolo [2,3 -b]pyrazine-7-carboxylic acid [(R)-2- (3-cyano-azetidin-l -yl)-l -methyl-2-oxo-ethyl]-amide 2,4,6-Trichlorobenzaldehyde was prepared according to the procedure outlined in Synthesis 2008, 279. To a solution of 1 ,3,5 -trichlorobenzene (10.0 g, 55.1 mmol) in THF (200 ml) at -78C was slowly added n-BuLi (1.6 M in hexanes, 34.4 ml, 55.1 mmol) over 20 min. The reaction mixture was stirred at -78C for 30 min then DMF (7.5 ml, 96.4 mmol) was added dropwise. The reaction was stirred at -78C for an additional 1.5 h then quenched with 3 N HC1 (200 ml) and warmed to room temperature. The mixture was extracted with EtOAc. The organic layer was washed with sat NaHCC”3 and brine then dried over MgSC^ and concentrated to afford 10.7 g (93%) of 2,4,6-trichlorobenzaldehyde as a white solid.

The chemical industry reduces the impact on the environment during synthesis 1,3,5-Trichlorobenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; CHEN, Shaoqing; DE VICENTE FIDALGO, Javier; HAMILTON, Matthew Michael; HERMANN, Johannes Cornelius; KENNEDY-SMITH, Joshua; LI, Hongju; LOVEY, Allen John; LUCAS, Matthew C.; LUK, Kin-Chun Thomas; LYNCH, Stephen M.; O’YANG, Counde; PADILLA, Fernando; SCHOENFELD, Ryan Craig; SIDDURI, Achyutharao; SOTH, Michael; WANG, Ce; WOVKULICH, Peter Michael; ZHANG, Xiaohu; WO2013/30138; (2013); A1;,
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432-21-3, 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 432-21-3 as follows.

1-Chloro-3-iodo-2-trifluoromethyl-benzeneTo a suspension of 3-Chloro-2-trifluoromethyl-phenylamine hydrochloride (30.9 g, iQ 0.16 mol) in H2O (90 mL) was added cone. HCI (65 mL) portion wise allowing the reaction to heat up to -45 0C. The temperature was maintained for 30 min then cooled in an ice bath < 5 0C. CH2CI2 (10 mL) was added and -10 min later a solution of sodium nitrite (13.6 g, 0.197 mol) in H2O (25 mL) was added dropwise. After a further 30 min, a solution of NaI (28.2 g, 0.188 mol) in H2O (50 mL) was again added dropwise keeping the temperature < 5 0C j 5 throughout both additions. After -1 h the reaction was diluted with CH2CI2 (200 mL) and sodium metabisulfite was added until the I2 color had been discharged. The layers were separated and the organic washed with brine, dried and the solvent evaporated to give 1- Chloro-3-iodo-2-trifluoromethyl-benzene (38.3 g, 79%) as an orange solid, which was used without further purification. MS: APCI: M+: 306.0 (305.9) At the same time, in my other blogs, there are other synthetic methods of this type of compound, 432-21-3, and friends who are interested can also refer to it. Reference:
Patent; PFIZER PRODUCTS INC.; WO2008/20306; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

81927-55-1,Some common heterocyclic compound, 81927-55-1, name is Benzyl 2,2,2-trichloroacetimidate, molecular formula is C9H8Cl3NO, 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 alcohol 5 (1.00 g, 8.61 mol) and benzyl 2,2,2-trichloroacetimidate26 (4.34 g, 17.2 mmol, 2.0 equiv) in 1,4-dioxane (15 mL) was added trifluoromethanesulfonic acid (0.15 mL, 1.72 mmol, 0.2 equiv) dropwise at room temperature under nitrogen. The reaction was stirred at room temperature for 1.5 h. The mixture was diluted with dichloromethane (35 mL), washed with saturated aqueous solution of sodium bicarbonate (25 mL*2) and brine (25 mL*3), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel (petroleum ether/ethyl acetate 5:1 to 2:1) to afford the titled compound as colorless oil (1.60 g, 90%). The 1H NMR spectrum was identical to literature data. 1H NMR (400 MHz, CDCl3) delta 7.30-7.19 (m, 5H), 4.62-4.54 (m, 1H), 4.56 (d, J=2.9 Hz, 2H), 3.59 and 3.49 (ABX, JAB=10.8 Hz, JAx=3.3 Hz, JBx=4.3 Hz, 2H), 2.59-2.34 (m, 2H), 2.26-2.13 (m, 1H), 2.09-1.97 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Benzyl 2,2,2-trichloroacetimidate, its application will become more common.

Reference:
Article; Yang, Fan; Feng, Liang; Wang, Nengzhong; Liu, Xuge; Li, Jun; Shen, Yuehai; Tetrahedron; vol. 69; 45; (2013); p. 9463 – 9468;,
Chloride – Wikipedia,
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Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 112-26-5, name is 1,2-Bis(2-chloroethoxy)ethane, This compound has unique chemical properties. The synthetic route is as follows., 112-26-5

General procedure: A suspension of 4 (1.0g, 3.45mmol) and K2CO3 (0.47g, 3.45 mmol) in acetonitrile (20mL) was heated to 85oC. bis(2-chloroethyl) ether (0.49 g, 3.45 mmol) in acetonitrile (2.0 mL) was added dropwise over 3 h. The mixture was heated at 85oC for 36 h, cooled,and acetonitrile was removed in vacuum. The residue was acidified with dil. HCl (0.45M, 200 mL). The aqueous layer was extracted with chloroform (2¡Á20 mL). The chloroformlayer was dried over Na2SO4 and the solvent evaporated in vacuum to give an oily compound which was purified by column chromatography on silica gel using ethyl acetate: pet ether (2:8 v/v) (7)

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Article; Utekar, Druman R.; Samant, Shriniwas D.; Journal of the Korean Chemical Society; vol. 58; 2; (2014); p. 193 – 197;,
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Chlorides – an overview | ScienceDirect Topics

A common heterocyclic compound, 13078-79-0, name is 2-(3-Chlorophenyl)ethanamine, molecular formula is C8H10ClN, 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. 13078-79-0.

General procedure: To compound 5, 6 or 7 (1 equiv) and the appropriate alkylamine(1.3 equiv) in anhydrous DMF (10 mL/mmol) were added DIEA (3equiv) and PyBOP (1 equiv), and the reaction mixturewas stirred atroom temperature under argon. When the reaction was complete(2 h – 4 h), the solvents were removed under reduced pressure togive a residue that was taken up in CH2Cl2. The solution waswashed with saturated aqueous NaHCO3, then water. The organiclayer was dried over Na2SO4 and then evaporated in vacuo. Purificationby flash chromatography afforded the corresponding amidederivatives 8, 9 or 10 (yield: 40-76%).

The synthetic route of 2-(3-Chlorophenyl)ethanamine has been constantly updated, and we look forward to future research findings.

Reference:
Article; Paoletti, Julie; Assairi, Liliane; Gelin, Muriel; Huteau, Valerie; Nahori, Marie-Anne; Dussurget, Olivier; Labesse, Gilles; Pochet, Sylvie; European Journal of Medicinal Chemistry; vol. 124; (2016); p. 1041 – 1056;,
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5013-77-4, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 5013-77-4, name is N-Methyl-2,4-dichlorobenzylamine, This compound has unique chemical properties. The synthetic route is as follows.

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-bromo 1 -phenyl ethanone (1 g, 5 05 mmol, 1 00 equiv) in 1,4-dioxane (20 mL) and (2,4-dichlorophenyl)-N-methylmethanamme (1 1 g, 5 82 mmol, 1 15 equiv) T?ethylamine (2 g, 19 80 mmol, 3 92 equiv) was added dropwise with stirring at 2O0C The resulting solution was stirred for 1 h at 2O0C in an oil bath The solids were filtered out The resulting mixture was concentrated under vacuum The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 50) This resulted in 1 4 g (90%) of the title compound as a yellow oil.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; ARDELYX, INC.; CHARMOT, Dominique; JACOBS, Jeffrey, W.; LEADBETTER, Michael, Robert; NAVRE, Marc; CARRERAS, Chris; BELL, Noah; WO2010/78449; (2010); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics