Author: Jessica.F

These common heterocyclic compound, 1939-99-7, name is Phenylmethanesulfonyl chloride, 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. name: Phenylmethanesulfonyl chloride

Synthesis of Ethyl 1-(benzylsulfonyl)piperidine-2-carboxylate (Ref .1 ) Ethyl piperidine-2-carboxylate (100mg, 0.63 mmol) was dissolved in 5mL of anhydrous DMF, and triethylamine (191mg, 1.89 mmol) was added drop wise followed by phenylmethanesulfonyl chloride (119.7mg, 0.63 mmol). The reaction was stirred for 6h at RT and subsequently the solvent was removed in vacuo. The crude mixture was purified using column chromatography (hexane : EtOAc 8:2) to yield Ethyl 1-(benzylsulfonyl)piperidine-2-carboxylate_(170mg, 0.55 mmol, 86%). TLC (hexane: EtOAc 8:2): Rf = 0.20. HPLC (gradient A) retention time= 23.4-23.8 min 1 HNMR (300 MHz, CDCI3) delta= 1 .14-1 .25 (m, 1 H), 1 .28 (t, 3H, J= 7.2 Hz), 1 .34-1 .49 (m, 1 H), 1 .54-1 .68 (m, 3H), 2.14 (d, 1 H, J= 13.5 Hz), 3.14 (dt, 1 H, J= 3.3, 12.6 Hz), 3.44 (d, 1 H, J= 12.6 Hz), 4.18-4.24 (m, 2H), 4.26 (s, 2H), 4.54 (d, 1 H, J= 4.8 Hz), 7.31 -7.38 (m, 3H), 7.43-7.48 (m, 2H). 13C NMR (75 MHz, CDCI3) delta= 14.22, 20.31 , 25.04, 27.78, 43.39, 55.95, 58.71 , 61 .36, 128.40, 128.48, 129.35, 130.96, 171 .38. MS (ESI) m/z: found Rt 14.28 min. (Method LCMS), 312.12 [M + H] +, 334.22 [M + Na] +. calculated 312.12 [M + H] +, 334.1 1 [M + Na] +.

The synthetic route of Phenylmethanesulfonyl chloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MAX-PLANCK-GESELLSCHAFT ZUR FOeRDERUNG DER WISSENSCHAFTEN E.V.; GOPALAKRISHNAN, Ranganath; HAUSCH, Felix; WO2013/97947; (2013); A1;,
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Synthetic Route of 56961-77-4,Some common heterocyclic compound, 56961-77-4, name is 1-Bromo-2,3-dichlorobenzene, molecular formula is C6H3BrCl2, 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.

Under a nitrogen atmosphere, and added at 120 will have the N 1 , the N 1 ,the N 3 – triphenyl benzene-1,3-diamine (20.0g), 1- bromo-2,3-dichlorobenzene ( 6.4g),Pd-132 (0.2g ), NaOtBu (6.8g) and xylene (70ml) was stirred for 2 hours the flask washeated. The reaction mixture was cooled until room temperature, water and ethyl acetateto carry out a liquid. Then, the use of silica gel column chromatography (eluent:toluene / heptane = 4/6 (volume ratio)) to be purified, to thereby obtain the N 1 , theN 1 ‘ – (2- chloro-1,3-phenylene yl) bis (the N 1 , the N 3 , the N 3 – phenyl-trityl-1,3-diamine) (15.0g)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-2,3-dichlorobenzene, its application will become more common.

Reference:
Patent; Kwansei Gakuin School Corporation; Tian, Shanzuoci; Zhong, Zhongzongyiliang; Zhong, Daoguiyi; Ping, Jingdagui; Xiao, Yeyangping; Zhi, Lianyizhi; Ni, Jingping; Song, Xiawusi; Sheng, Tianlizhao; (405 pag.)CN105431439; (2016); A;,
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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. 93-50-5, name is 4-Chloro-2-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 4-Chloro-2-methoxyaniline

Step 1: In a sealed tube 4-chloro-2-anisidine (3.0 g, 19.0 mmol), 5-chloro-2-trifluromethylpyridine (3.8 g, 20.9 mmol) and Cs2C03 (8.02 g, 24.7 mmol) were mixed in toluene (50 mL). The resulting mixture was purged with nitrogen, added Pd(OAc)2 (0.64 g, 2.8 mmol) and X-phos (0.45 g, 0.95 mmol) and heated at 140 C for 12 h. After completion of the reaction, the reaction mixture was filtered through Celite bed and concentrated under vacuum. The residue obtained was diluted with ethyl acetate (200 mL), washed with water, brine solution and dried over anhydrous Na2S04. The organic phase was concentrated and purified by the column chromatography (230-400 size mesh) to get the desired product /V-(4-chloro-2-methoxyphenyl)-6- (trifluoromethyl)pyridin-3-amine (3.5 g, 61.4%). LC MS: 303.0 (M+H), RT- 3.45 min, 96.03% (max) Method A-0.1% HCOOH; B-ACN Flow = 1.5 mU in. Column-ZORBAX XDB C18 (50X 4.6mm-5pm) positive Mode 1H NMR (300 MHz, DMSO-d6) : delta 8.42 (s, 1H), 8.27 (d, J = 2.58 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.21-7.27 (m, 2H), 7.16 (d, J = 2.16 Hz, 1H), 6.97 (dd, J = 2.17, 9.80 Hz, 1 H), 3.81 (s, 3H).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 93-50-5.

Reference:
Patent; MERCK PATENT GMBH; SPANGENBERG, Thomas; (129 pag.)WO2016/827; (2016); A1;,
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Adding a certain compound to certain chemical reactions, such as: 2533-69-9, name is Methyl 2,2,2-trichloroacetimidate, 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 2533-69-9, Product Details of 2533-69-9

(a) 2-Trichloromethyl-6-trifluoromethyl-1H-benzoimidazole. To a solution of 4-trifluoromethyl-benzene-1,2-diamine (1.76 g, 10 mmol, Lancaster) in DCM (20 mL) was added methyl 2,2,2-trichloroacetimidate (1.94 g, 11 mmol, Aldrich) and glacial acetic acid (3 mL) with stirring at room temperature. The reaction mixture was stirred at room temperature for 16 h and concentrated in vacuo. The residue was purified by silica gel column chromatography (35% EtOAc/hexane) to give the title compound as a brown solid. MS (ESI, pos. ion) m/z: 303 (M+1).

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

Reference:
Patent; Hulme, Christopher; Ncube, Mghele Vellah; Norman, Mark H.; Ognyanov, Vassil I.; Pettus, Liping H.; Wang, Xianghong; Zhu, Jiawang; US2005/165049; (2005); A1;,
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Related Products of 870-24-6, 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. 870-24-6 name is 2-Chloroethanamine hydrochloride, 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.

Analog 5, N-(2-Chloroethyl)arachidonylamide. A solution of arachidonic acid (50 mg, 0.165 mmol) and 0.03 mL of anhydrous DMF in 1 mL of dry dichloromethane was cooled in an ice bath under argon and 0.17 mL of a 2 M solution of oxalyl chloride (0.34 mmol) in dichloromethane was added dropwise. Reaction mixture was stirred further at ice bath temperature for 1 hour. A solution of 65 mg (0.50 mmol, 3 equiv) of 2-chloroethylamine hydrochloride in 0.5 mL of dry pyridine was added, the cooling bath was removed, and the solution was stirred at room temperature for 30 min. The mixture was transferred to a separatory funnel, washed with 10% aqueous hydrochloric acid and water, and dried (MgSO4). After rotary evaporation of solvents, the residue was chromatographed on silica gel (60% ethyl ether-petroleum ether) to afford 54 mg (90%) of the pure title compound as an oil: Rf (70% ethyl ether-petroleum ether) 0.35; 1H NMR (270 MHZ, CDCl3) 5.80 (br s, 1H), 5.36 (m, 8H), 3.61 (m, 4H), 2.80 (m, 6H), 2.21 (t, J=7.89 Hz, 2H), 2.10 (m, 4H), 1.72 (m, 2H), 1.29 (m, 6H), 0.88 (t, J=6.79 Hz, 3H). Anal. (C22H36CINO) C, H, N.

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

Reference:
Patent; University of Connecticut; US7161016; (2007); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 96558-78-0, 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 96558-78-0 as follows.

3-Bromo-5-chloroaniline (20 g, 96.87 mmol) was added dropwise to 103 N-chlorosuccinimide (12.93 g, 96.87 mmol) in 52 DMF (100 mL) at rt. The resulting solution was stirred at rt for 16 h. The solvent was removed in vacuo. The crude product obtained was purified by flash silica chromatography (5 to 10% 57 EtOAc in 148 petroleum ether) to afford 687 3-bromo-4,5-dichloroaniline (8 g, 34%) as a brown solid; 1H NMR (300 MHz, DMSO, 30 C.) 6.02 (2H, s), 6.83 (1H, d), 6.94 (1H, d); m/z: ES+ [M+H]+=242.

According to the analysis of related databases, 96558-78-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); A1;,
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Electric Literature of 139512-70-2, 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 139512-70-2 as follows.

General procedure: Intermediate compound 5 (0.2 g, 1.24 mmol) and benzil 6d (0.26 g, 1.24 mmol) were weighed and dissolved in 20 mL glacial acetic acid. This mixture was refluxed for 2.5hr. The completion of reaction was monitored by TLC. The reaction mixture was cooled and poured into crushed ice. The precipitated product was filtered off and washed with cold water. The product was then purified by column chromatography using hexane: ethyl acetate as mobile phase. The pure fractions obtained were dried and concentrated to obtain white solids of product 7d. (yield 82%, m.p. 110-112 C).

According to the analysis of related databases, 139512-70-2, the application of this compound in the production field has become more and more popular.

Reference:
Article; Patel, Saloni B.; Patel, Bhumika D.; Pannecouque, Christophe; Bhatt, Hardik G.; European Journal of Medicinal Chemistry; vol. 117; (2016); p. 230 – 240;,
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Reference of 883499-24-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 883499-24-9, name is 1-Bromo-2-chloro-3-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of l-brmo-2-chloro-3-fluoro benzene (1.0 g, 4.79 mmol) in toluene (20mL) were added phenyl boronic acid(875 mg, 7.18 mmol), Na2C03 (1.52 g, 14.35 mmol),water (5 mL) and degassed for 10 min in argon atmosphere. Then to it was added Pd(PPh3)4 (553 mg, 0.48 mmol) and again degassed for 5 min. The reaction was heated to 100C for 16 h. The reaction mixture was then cooled to 25C, filtered through celite and washed with ethyl acetate. The separated organic layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to get the crude product which was purified by combiflash column chromatography using hexane to get 2-chloro-l-fluoro-3- phenylbenzene (920 mg, 93%) as yellow, sticky liquid.

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, 1-Bromo-2-chloro-3-fluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ALANINE, Alexander; AMREIN, Kurt; BLEICHER, Konrad; FASCHING, Bernhard; HILPERT, Hans; KOLCZEWSKI, Sabine; KROLL, Carsten; SCHAEUBLIN, Adrian; ZAMPALONI, Claudia; (176 pag.)WO2018/189065; (2018); 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. 699-89-8, name is 4,7-Dichlorothieno[2,3-d]pyridazine, This compound has unique chemical properties. The synthetic route is as follows., name: 4,7-Dichlorothieno[2,3-d]pyridazine

One equivalent of dichloride (1) and 2.2 equivalent of M-NH2 are refluxed in an appropriate amount of n-butanol at 150C for 10 hrs. The reaction mixture is allowed to cool to room temperature and the precipitate (4) that forms is filtered and washed sequentially with isopropyl alcohol, 4.0 N KOH, H2O, and hexane, and then dried. The crude product (4) is purified by preparative TLC or flash chromatography on silica gel using dichloromethane/methanol (95:5) as the eluent. Final product is confirmed by LC/MS and/or NMR. The invention compounds of Examples 26 – 33 and 75 as shown in the below table were prepared by method A-2.

According to the analysis of related databases, 699-89-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER CORPORATION; EP1228063; (2009); B1;,
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Synthetic Route of 20816-79-9, A common heterocyclic compound, 20816-79-9, name is 1-Bromo-8-chloronaphthalene, molecular formula is C10H6BrCl, 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 benzyl (2S)-2-(cyanomethyl)-4-[2-[[(2,S)-l – methylpyrrolidin-2-yl]methoxy]-6,7,8,9-tetrahydro-5/7-pyrimido[4,5-c]azepin-4-yl]piperazine-l – carboxylate (250 mg. 481 pmol, 1.0 eq) and l-bromo-8-chloro- naphthalene (232 mg, 962 pmol, 2.0 eq) in toluene (4.0 mL) was added RuPhos (89.8 mg, 192 pmol, 0.4 eq), CS2CO3 (392 mg, 1.20 mmol, 2.5 eq) and Pd2(dba)3 (88.1 mg, 96.2 pmol, 0.2 eq), the reaction mixture was stirred at 90 C for 10 hours under N2. After completion, the reaction mixture was filtered through a celite, the filter cake was washed with ethyl acetate (10 mL), and adjusted with 1N HC1 aqueous to pH~3, the organic layer was separated, and the aqueous was adjusted with Na2C03 solid to pi 1 8. extracted with ethyl acetate (2 x 10 mL), the organic layer was washed with saturated brine (1 c 20 mL), dried over Na2S04, filtered and concentrated. The residue was purified by reverse phase flash (Cl 8, 0.1 %FA in water, 30%-50% MeCN). The product benzyl (25 -4-[8-(8- chloro-l-naphthyl)-2-[[(25)-l -methylpyrrolidin-2-yl] methoxy]-5,6,7,9-tetrahydropyrimido[4,5- c]azepin-4-yl]-2-(cyanomethyl)piperazine-l-carboxylate (130 mg, 185 pmol, 38% yield, 97% purity) was obtained as yellow solid. LCMS [ES1, M+l]: 680. (0587) [0348] NMR (400 MHz, chloroform-d) d 7.74 – 7.68 (m, 1H), 7.59 – 7.51 (m, 1H), 7.48 – 7.15 (m, 9H), 5.21 (s, 2H), 4.74 – 4.63 (m, 1H), 4.40 – 4.29 (m, 211), 4.21 – 4.05 (m, 211), 3.84 – 3.71 (m, 1 H), 3.69 – 3.46 (m, 2H), 3.44 – 3.15 (m, 3LI), 3.13 – 2.60 (m, 8H), 2.46 (s, 3H), 2.33 – 2.21 (m, 1 H), 2.17 – 2.02 (m, 2H), 1.96 – 1.72 (m, 4H). LCMS [ESI, M+l]: 546.

The synthetic route of 20816-79-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MIRATI THERAPEUTICS, INC.; ARRAY BIOPHARMA, INC.; MARX, Matthew, Arnold; BLAKE, James, F.; FELL, Jay, Bradford; FISCHER, John, P.; MEJIA, Macedonio, J.; (164 pag.)WO2020/47192; (2020); A1;,
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