Month: March 2021

Synthetic Route of 51419-59-1, The chemical industry reduces the impact on the environment during synthesis 51419-59-1, name is p-Tolylmethanesulfonyl chloride, I believe this compound will play a more active role in future production and life.

Ethyl (2E)-3-(2-fluoro-5-nitrophenyl)acrylate (1000 mg, 4.18 mmol) and 1,1?-bi(cyclopropyl)-l-amine (508 mg, 3.80 mmol) were dissolved under argon in abs. N,N-dimethylformamide (10 mE), and then N,N-diisopropylethylamine (1.32 mE, 7.60 mmol) was added. The resulting reaction mixture was stirred at a temperature of 50 C. for a total of 16 h and, afier cooling to room temperature, water and ethyl acetate were added. The aqueous phase was then extracted repeatedly with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), ethyl (2E)-3-{2-[ 1, 1?-bi(cyclopro- pyl)- 1 -ylamino]-5-nitrophenyl}acrylate (570 mg, 43% of theory) was isolated as a colorless solid, ?H-NMR (400 MHz, CDC13 oe, ppm) 8.27 (d, 1H), 8.16 (m, 1H), 7.63 (d, 1H), 7.18 (d, 1H), 6.46 (d, 1H), 5.19 (br. s, 1H, NH), 4.29 (q, 2H), 1.35 (t, 3H), 1.33-1.27 (m, 1H), 0.78 (m, 4H), 0.49 (m, 2H), 0.18 (m, 2H). Ethyl (2E)-3-{2-[i,i?-bi(cyclopro- pyl)- 1 -ylamino]-5-nitrophenyl}acrylate (570 mg, 1.80 mmol) was then dissolved in abs. ethanol (10 mE), and (Ph3P)3RhC1 (167 mg, 0.18 mmol) was added. After stirring at room temperature for 5 mm, hydrogen was introduced into the reaction solution with a constant gas flow via a gas introduction apparatus for about 9 h. The progress of the reaction was monitored by EC-MS. On completion of conversion, the reaction solution was concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), it was possible to isolate ethyl 3-{2-[1,1?-bi(cyclopro- pyl)- 1 -ylamino]-5-nitrophenyl}propanoate (200 mg, 35% of theory) as a colorless solid, ?H-NMR (400 MHz, CDC13 oe, ppm) 8.07 (m, 1H), 7.94 (d, 1H), 7.11 (d, 1H), 5.40 (bt 5, 1H, NH), 4.18 (q, 2H), 2.77 (m, 2H), 2.64 (m, 2H), 1.30-1.24 (m, 4H), 0.76 (m, 4H), 0.46 (m, 2H), 0.17 (m, 2H). Ethyl 3-{2-[ 1, 1?-bi(cyclopropyl)- 1 -ylamino]-5-nitrophenyl}propanoate (200 mg, 0.63 mmol) was dissolved in abs. tetrahydroffiran (8 mE) and added dropwise to a suspension, cooled down to 0 C., of sodium hydride (38 mg, 0.94 mmol, 60% suspension in oil) in abs. tetrahydrothran (5 mE) under argon. The resulting reaction mixture was stirred at 0 C. for 1 h, and then water was added cautiously, followed by ethyl acetate afier stirring for 5 mm. The aqueous phase was then extracted repeatedly with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1 -[1, 1?-bi(cyclopropyl)- 1 -yl] -6-nitro-3,4-dihydroquinolin-2 (1H)-one (90 mg, 53%) was isolated as a colorless solid, ?H-NMR (400 MHz, CDC13 oe, ppm) 8.16 (m, 1H), 8.04 (m, 1H), 7.53 (d, 1H), 2.93 (m, 2H), 2.78-2.58 (m, 2H), 1.44 (m, 1H), 1.23 (m, 1H), 1.03 (m, 1H), 0.91-0.82 (m, 2H),0.60-0.45 (m, 3H), 0.28 (m, 1H). In the next step, 1-[1,1?- bi(cyclopropyl)-1 -yl] -6-nitro-3,4-dihydroquinolin-2(1H)-one (90 mg, 0.33 mmol) was added together with tin(II) chloride dihydrate (298 mg, 1.32 mmol) to abs. ethanol (5 mE) and the mixture was stirred under argon at a temperature of 80 C. for 5 h. After cooling to room temperature, the reaction mixture was poured into ice-water and then adjusted to pH 12 using aqueous NaOH. The aqueous phase was then extracted repeatedly with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By colunm chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 6-amino-i -[1,1 ?-bi(cyclopropyl)- 1 -yl]-3,4-dihydroquinolin-2(1H)-one (70 mg, 87% of theory) was isolated as a highly viscous foam, ?H-NMR (400 MHz, CDC13 oe, ppm) 7.18 (m, 1H), 6.58 (m, 1H), 6.48 (d, 1H), 2.78 (m, 2H), 2.59 (m, 2H), 1.47 (m, 1H), 1.08 (m, 1H), 0.98 (m, 1H), 0.90-0.81 (m, 2H), 0.60-0.43 (m, 3H),0.28 (m, 1H). 6-Amino-i -[1 ,i?-bi(cyclopropyl)-i -yl]-3,4-di- hydroquinolin-2(1H)-one (70 mg, 0.29 mmol) was dissolved together with (4-methylphenyl)methanesulfonyl chloride (65 mg, 0.32 mmol) in abs. acetonitrile (5 mE) in a baked- out round-bottom flask under argon, then pyridine (0.05 mE, 0.58 mmol) was added and the mixture was stirred at room temperature for 8 h. The reaction mixture was then concentrated under reduced pressure, the remaining residue was admixed with dil. HC1 and dichloromethane, and the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By colunm chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), N-{ 1 -[1,1 ?-bi(cyclopropyl)-i -yl]-2-oxo-i ,2,3,4-tetrahydroquinolin-6-yl}-i -(4-methylphenyl)methanesulfonamide (32 mg, 27% oftheory) was isolated as …

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, p-Tolylmethanesulfonyl chloride, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BAYER CROPSCIENCE AKTIENGESELLSCHAFT; FRACKENPOHL, JENS; BOJACK, GUIDO; HELMKE, HENDRIK; WILLMS, LOTHAR; LEHR, STEFAN; MUELLER, THOMAS; DITTGEN, JAN; SCHMUTZLER, DIRK; BALTZ, RACHEL; BICKERS, UDO; (119 pag.)US2018/20662; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2401-24-3, These common heterocyclic compound, 2401-24-3, name is 2-Chloro-5-methoxyaniline, 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.

EXAMPLE 113 4-(2-Chloro-5-methoxyanilino)-2,6-di(2-pyridinyl)pyrimidine The title compound was prepared from a mixture of 4-chloro-2,6-di(2-pyridinyl)pyrimidine (25 mg, 0.093 mmol) and 2-chloro-5-methoxyaniline (27 mg, 0.140 mmol) similar to Example 111 and isolated as a white solid (20 mg, 55%). 1H NMR (CDCl3): 8.87-8.82 (m, 1H), 8.72-8.64 (m, 3H), 8.08 (d, J=2.7 Hz, 1H), 7.92 (s, 1H), 7.90-7.86 (m, 2H), 7.45-7.38 (m, 3H), 7.33 (d, J=8.7 Hz, 1H), 6.67 (dd, J=3.0, 9.0 Hz, 1H), 3.91 (s, 3H).

The synthetic route of 2401-24-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cytovia, Inc.; US2003/69239; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 33786-89-9, 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. 33786-89-9 name is 5-Chloro-m-phenylenediamine, 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.

EXAMPLE 1 In an autoclave, 3.3 g. of 3,5-diaminochlorobenzene, 0.2 g. of cuprous chloride and 10 g. of liquid ammonia were charged to react them at 170 to 175 C. for 5 hours. After the reaction, the unreacted ammonia was discharged and a greyish black crystal was obtained. The product was purified by a silica gel column chromatography to obtain 1.7 g. of 1,3,5-triaminobenzene.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloro-m-phenylenediamine, and friends who are interested can also refer to it.

Reference:
Patent; Ishihara Sangyo Kaisha Ltd.; US4380670; (1983); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 63624-28-2, 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. 63624-28-2, name is 2,4-Dimethoxybenzene-1-sulfonyl chloride, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a solution of hydrogen chloride gas in dry ethyl acetate (1.5 M,3.0 mL) was added intermediate IM 3 (0.3 g, 0.6 mmol). The reactionmixture was stirred for 4 h at room temperature. The solvent was removedunder reduced pressure to give solid deprotected product.Various substituted-phenyl sulfonyl chlorides were added dropwise in a mixture of deprotected product and triethylamine (0.5 mL) in anhydrousCH2Cl2 (10 mL). After stirring at room temperature overnight, thereaction mixture was concentrated using a rotary evaporator. The crudeproduct was purified by chromatography on silica gel utilized a mixtureof chloroform and acetone (35:1, v/v) as eluent to furnish the desiredproduct.

The chemical industry reduces the impact on the environment during synthesis 2,4-Dimethoxybenzene-1-sulfonyl chloride. I believe this compound will play a more active role in future production and life.

Reference:
Article; Yuan, Lei; Liu, Jun; He, Wenhui; Bao, Youmei; Sheng, Lei; Zou, Chunyang; Hu, Baichun; Ge, Wentao; Liu, Yang; Wang, Jian; Lin, Bin; Li, Yanchun; Ma, Enlong; Bioorganic Chemistry; vol. 84; (2019); p. 239 – 253;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2106-02-7, 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. 2106-02-7 name is 2-Chloro-4-fluoroaniline, 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.

Concentrated nitric acid (8.8 g, 91 mmol) was added drop wise over 30 min to a stirred solution of 2-chloro-4-fluoro-phenylamine (12 g, 82.3 mmol) in cone H2SO4 acid (100 mL) at -10 0C. The mixture was stirred at that temperature for 10 min. Then the reaction mixture was poured into cooled EtOAc, and ice water was added. The organic layer was separated and washed with brine and saturated NaHCO3 solution, dried (MgSO4) and concentrated in vacuo. Recrystallization (ethyl ether) provided 2-chloro-4-fluoro-5-nitroaniline (5.0 g, 32% yield). 1H NMR (400 MHz, DMSO-rftf): (57.59 (d, J= 11.2 Hz, 1 H)5 7.48 (d, J= 7.2 Hz, 1 H), 5.84 (s, 2 H).

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

Reference:
Patent; DECIPHERA PHARMACEUTICALS, LLC; WO2008/33999; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, belongs to chlorides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. HPLC of Formula: C6H3BrClF

A solution of 1-bromo-4-chloro-2-fluoro-benzene (59c, 0.415 g, 1.98 mmol), 6 (0.350 g, 1.8 mmol), K2CO3 (0.746 g, 5.4 mmol) and NMP (4 mL) was stirred and heated to 120 C. for 6 h. The reaction mixture was cooled to RT and diluted with H2O (25 mL) and twice extracted with EtOAc. The combined organic extracts were washed sequentially with water (6 times) and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 column chromatography eluting with a EtOAc/hexane (100% to 75% hexane) to afford 116a

The synthetic route of 1996-29-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Roche Palo Alto LLC; US2005/239881; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene, belongs to chlorides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 1996-30-1, Application In Synthesis of 3-Bromo-4-fluorochlorobenzene

2-Bromo-6-chloro-3-fluoro-benzaldehyde: To a -78 C. solution of 2-Bromo-4-chloro-1-fluoro-benzene (2.90 g, 13.9 mmol) in 30 mL tetrahydrofuran under an atmosphere of nitrogen was added lithium diisopropylamide solution (1.8M in tetrahydrofuran/heptane/ethylbenzene, 10.0 mL, 18.0 mmol) at such a rate that the internal reaction temperature did not exceed -69 C. After 1 hour at -78 C., dimethylformamide (1.39 mL, 18.0 mmol) was added at such a rate that the internal temperature did not exceed -69 C. After 30 minutes at -78 C., the reaction was quenched with saturated aqueous ammonium hydroxide solution. The resulting mixture was extracted with diethyl ether. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution with 0 to 5% ethylacetate/hexanes) to yield 2-Bromo-6-chloro-3-fluoro-benzaldehyde (440 mg, 1.85 mmol). MS (ESI) 236.9 (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; Berthel, Steven; Firooznia, Fariborz; Fishlock, Daniel; Hong, Jun-Bae; Lou, Yan; Lucas, Matthew; Owens, Timothy D.; Sarma, Keshab; Sweeney, Zachary Kevin; Taygerly, Joshua Paul Gergely; US2010/222325; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 26487-67-2, name is 1-(2-Chloroethyl)azepane hydrochloride, molecular formula is C8H17Cl2N, 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. Quality Control of 1-(2-Chloroethyl)azepane hydrochloride

Example 7 1-(2-(1-Perhydroazepinyl)ethyl)-3,4-dimethyl-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidine A solution of 1-(2-chloroethyl)perhydroazepine hydrochloride (42 mg, 0.21 mmol) in N,N-dimethylformamide (1 mL) was treated with triethylamine (30 muL, 0.22 mmol) then transferred to a flask containing 3,4-dimethyl-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidine (Preparation 44, 45 mg, 0.176 mmol) in N,N-dimethylformamide (2 mL). Sodium iodide (32 mg, 0.21 mmol) and sodium hydrogencarbonate (18 mg, 0.21 mmol) were added and the resultant mixture was heated at 60¡ã C. overnight. The solvent was then removed in vacuo and the residue was partitioned between saturated aqueous sodium hydrogencarbonate solution (5 mL) and dichloromethane (5 mL). The phases were separated and the aqueous layer was further extracted with dichloromethane (2*5 mL). The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by reversed phase preparative HPLC (condition 2) to give the acetate salt of the title compound. The free base was obtained by treating with dilute aqueous ammonia solution (2 mL) and extracting with ether (4*3 mL). Drying over Na2SO4, filtering and evaporation to dryness gave the title compound as a white solid (16 mg, 24percent). NMR (CDCl3, selected data for the free base): 0.8 (d, 3H), 1.35 (s, 3H), 1.6-1.8 (m, 9H), 2.10 (m, 1H), 2.4-2.5 (m, 2H), 2.6-3.0 (m, 11H), 7.25 (d, 1H), 7.35 (t, 1H), 7.55 (d, 1H), 7.85 (s, 1H), 7.95 (s, 1H). MS (thermospray): M/Z (MH+) 382.6; C23H35N5+H requires 382.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 26487-67-2, its application will become more common.

Reference:
Patent; Gibson, Stephen Paul; Tommasini, Ivan; Verrier, Kimberley; Dutton, Christopher James; Gethin, David Morris; Critcher, Douglas James; Armer, Richard Edward; US2003/4340; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 363-51-9,Some common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, molecular formula is C6H5ClFN, 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.

Step B: Preparation of l-Chloro-3-fluoro-2-isothiocyanatobenzene To a solution of 2-chloro-6-fluorobenzenamine (5.0 g, 34 mmol) in chlorobenzene (52 mL) was added carbonothioic dichloride (thiophosgene) (5.1 g, 45 mmol) and DMF (0.27 mL). The reaction mixture was refluxed for 2 h and then concentrated to leave the title compound as a brown oil (6.15 g), which was used in Step C without further purification. H NMR 5 7.18 (m, 2H), 7.07 (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 2-Chloro-6-fluoroaniline, its application will become more common.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; TAGGI, Andrew, Edmund; LONG, Jeffrey, Keith; BEREZNAK, James, Francis; WO2013/116251; (2013); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 7051-16-3, name is 1-Chloro-3,5-dimethoxybenzene, A new synthetic method of this compound is introduced below., category: chlorides-buliding-blocks

1-chloro-3,5-dimethoxybenzene (10.0 g, 58 mmol) and N-bromosuccinimide (10.3 g, 58 mmol)In 1,2-diethylene chloride (200 ml)After melting, the mixture is stirred at room temperature for 24 hours.After the reaction, the solvent was removed from the reaction solution through a rotary evaporator,After extraction with methylene chloride / distilled water, column chromatography was carried out using a methylene chloride / hexane mixed solvent as a developing solvent to obtain 13.3 g of intermediate 1

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; LG Chem, Ltd.; Dankook University Cheonan Campus Industry-Academic Cooperation Foundation; Gu Gi-dong; Lee Gi-gon; Keum Su-jeong; Kim Gong-gyeom; Lee U-cheol; Lee Chil-won; Cha Jae-ryeong; Joo Yun-seok; (37 pag.)KR2019/109846; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics