Month: August 2021

Synthetic Route of 41965-95-1,Some common heterocyclic compound, 41965-95-1, name is 3-Chloro-4-methoxybenzylamine Hydrochloride, molecular formula is C8H11Cl2NO, 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.

N,N-Diisopropylethylamine (4.0 mL, 22.9 mmol, 4.0 eq.) was added to a mixture of 28 (2.0 g, 5.23 mmol, 1.0 eq.) and (3-chloro-4-methoxyphenyl)methanamine hydrochloride [29] (1.8 g, 8.41 mmol, 1.6 eq) in n-propanol (40 mL). The resulting mixture was heated at reflux for 16 h. After cooling to room temperature, water (40 mL) was added to the reaction mixture. The formed precipitate was filtered, washed successively with water (20 mL) and ethanol (20 mL) and then dried in a desiccator to afford the desired product 29 (2.3 g, 4.44 mmol, 85%) as a white solid. Rf (SiO2, cyclohexane/ethyl acetate, 7/3, v/v): 0.48; Mp: 140-142 C; IR (cm-1): 1701 (nuC=O), 1320 (nuCF3), 1281 (nuC-O), 1110 (nuC-O), 1031 (nuC-O); 1H NMR (CDCl3, 400 MHz) delta 9.79 (brs, 1H, NH), 9.33 (s, 1H, H2), 8.41 (m, 1H, H5), 8.18 (d, 1H, 4JH7-H5 = 1.5 Hz, H7), 7.40 (d, 1H, 4JH2?-H6?= 2.2 Hz, H2?), 7.24 (m, 1H, H6?), 6.96 (d, 1H, 3JH5?-H6?= 8.5 Hz, H5?), 4.87 (d, 2H, 3JHd-NH = 5.9 Hz, Hd), 4.40 (q, 2H, 3JHb-Hc= 7.1 Hz, Hb), 3.92 (s, 3H, He), 1.41 (t, 3H, 3JHc-Hb= 7.1 Hz, Hc); 13C NMR (CDCl3, 100 MHz) delta 167.3 (Ca), 154.5 (C4), 154.1 (2C, C4?, C8a), 148.6 (C2), 131.1 (C1?), 130.2 (C2?), 129.6 (C6?), 127.9 (C7), 126.2 (C8), 125.2 (q, 2JC6-F = 33 Hz, C6), 123.8 (d, 1JCF3-F = 271 Hz, CF3), 123.4 (C3?), 121.6 (C5), 120.1 (C4a), 113.4 (C5?), 105.9 (C3), 61.5 (Cb), 56.6 (Ce), 49.9 (Cd), 14.4 (Cc); HRMS calculated for C21H1779Br35ClF3N2O3 [M+H]+ m/z 517.0141, found C21H1779Br35ClF3N2O3 [M+H]+ m/z 517.0150 (77%); C21H1781Br35ClF3N2O3 or C21H1779Br37ClF3N2O3 [M+H]+ m/z 519.0163 (100%); C21H1781Br37ClF3N2O3 [M+H]+ m/z 521.0134 (24%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloro-4-methoxybenzylamine Hydrochloride, its application will become more common.

Reference:
Article; Liu, Jianrong; Maisonial-Besset, Aurelie; Wenzel, Barbara; Canitrot, Damien; Baufond, Ariane; Chezal, Jean-Michel; Brust, Peter; Moreau, Emmanuel; European Journal of Medicinal Chemistry; vol. 136; (2017); p. 548 – 560;,
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Reference of 118-69-4, 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 118-69-4 as follows.

Example 1Preparation of DCDNTTo a 1 L 3-neck round bottom flask equipped with external ice cooling, mechanical stirrer, addition funnel, N2 inlet, and thermometer was added 174 g (2.76 mol) fuming nitric acid (d=1.54), followed by 350 g sulfuric acid and 659 g 30% oleum (2.0 molar equiv SO3) maintaining a temperature between 5 and 20 C. Subsequently, 199 g (1.23 mol) 1,3-dichlorotoluene (99% purity, Aldrich Chemical Company, Milwaukee, Wis., USA) was added over a time period of 3 h while maintaining a temperature between 0 C.-10 C. The ice bath was removed, and the reaction mixture was allowed to warm up to room temperature. It was then heated to 100 C. for about 2 h. To analyze the reaction mixture, a small sample of crude product was taken from the reaction vessel and poured into ice water. The crude product was extracted with methylene chloride. Analysis by GC indicated a reaction selectivity to 3,5-dinitro-2,6-dichlorotoluene of >97%. Subsequently, the reaction mixture was allowed to cool to room temperature over 2 h and then cooled to 5 C. over 30 min, after which it was filtered through a glass fritted funnel and washed with a little sulfuric acid followed by 200 mL H20. The wet cake contained about 20% water. After drying, 291 g of >99.5% pure DCDNT product (by 1H-NMR) was isolated (93.5% net yield).

According to the analysis of related databases, 118-69-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; US2010/160685; (2010); A1;,
Chloride – Wikipedia,
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Related Products of 1939-99-7, A common heterocyclic compound, 1939-99-7, name is Phenylmethanesulfonyl chloride, molecular formula is C7H7ClO2S, 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.

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 1HNMR (300 MHz, CDCl3) delta= 1.14-1.25 (m, 1H), 1.28 (t, 3H, J= 7.2 Hz), 1.34-1.49 (m, 1H), 1.54-1.68 (m, 3H), 2.14 (d, 1H, J= 13.5 Hz), 3.14 (dt, 1H, J= 3.3, 12.6 Hz), 3.44 (d, 1H, J= 12.6 Hz), 4.18-4.24 (m, 2H), 4.26 (s, 2H), 4.54 (d, 1H, J= 4.8 Hz), 7.31-7.38 (m, 3H), 7.43-7.48 (m, 2H). 13C NMR (75 MHz, CDCl3) 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]+, 334.11 [M + Na]+.

The synthetic route of 1939-99-7 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; EP2610245; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 51419-59-1, name is p-Tolylmethanesulfonyl chloride, molecular formula is C8H9ClO2S, 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. HPLC of Formula: C8H9ClO2S

To a solution of 6-Amino-l-ethyl-4-methyl-4H-3,l-benzoxazin-2-one (0.140 g, 0.678 mmol) in ethyl acetate (5 mL) was added NN-diisopropylethylamine (0.175 g, 1.35 mmol) and p-tolylmethanesulfonyl chloride (0.180 g, 0.882 mmol). The reaction mixture was stirred for 15 min, concentrated and purified by flash chromatography to give the desired product as a pale solid (54 mg, 21 percent). LCMS : 0.92 min; ES+ 375 (M+H+); lH NMR (CHLOROFORM-d, 400MHz): delta (ppm) 7.12-7.20 (m, 4H), 7.09 (d, IH), 6.92 (d,lH), 6.89 (s, IH), 6.65 (s, IH), 5.29 (q, lH), 4.28 (s, 2H), 3.95 (q, 2H), 2.34 (s, 3H), 1.63 (d, 3H), 1.34 (t, 3H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 51419-59-1, its application will become more common.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; SYNGENTA PARTICIPATIONS AG; CUTLER, Sean, R.; LACHIA, Mathilde, Denise; WENDEBORN, Sebastian, Volker; GODFREY, Christopher, Richard Ayles; SABBADIN, Davide; (82 pag.)WO2018/17490; (2018); A1;,
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6781-98-2, name is 2-Chloro-1,3-dimethylbenzene, 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. category: chlorides-buliding-blocks

General procedure: Under N2 atmosphere, KOtBu (1.3 equiv), toluene (1.0 mL), amines 5 (0.84 mmol), aryl chlorides 4 (0.7 mmol) and finally a solution of complex 3a (20?100muL, 0.01?0.05 molpercent, prepared from 0.014 mmol 3a in 4.0mL toluene) were successively added into a Schlenk reaction tube. The mixture was stirred vigorously at 110 °C for 24h. Then the solvent was removed under reduced pressure and the residue was purified by flash column chromatography (SiO2) to give the corresponding products.

The synthetic route of 6781-98-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Liu, Feng; Hu, Yuan-Yuan; Li, Di; Zhou, Quan; Lu, Jian-Mei; Tetrahedron; vol. 74; 39; (2018); p. 5683 – 5690;,
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Electric Literature of 13918-92-8, The chemical industry reduces the impact on the environment during synthesis 13918-92-8, name is 2,4-Difluorobenzene-1-sulfonyl chloride, I believe this compound will play a more active role in future production and life.

General procedure: To 5-(5-(5-Aminopyridin-3-yl)thiophen-2-yl)-2-methyl- isoindolin-1-one (49) (225 mg, 0.79 mmol) in dry pyridine (23 mL) under N2 at RT,was added dropwise, 2,4-difluorobenzenesulphonyl chloride (336 mg, 1.58 mmol) in CH2Cl2(3 mL) over 5 min. The suspension was heated to 45 C under N2 for 4 h., at which pointanother portion of 2,4-difluorobenzenesulphonyl chloride (169 mg, 0.79 mmol) in CH2Cl2 (2mL) was added. The whole mixture was left to stir for at 45 C under N2 for 16 h., then thesolvent removed under reduced pressure. The resulting residue was suspended in acetone (10mL), 1 M HCl (20 mL) added, and the entire mixture stirred for 10 minutes. The solid wasthen collected by filtration, washed well with 1 M HCl and water, dried, and purified bychromatography as described below. In cases where the bis-sulphonamide was also formed, a second step was introduced wherethe crude product above was treated with a 1:1 mixture of 1,4-dioxane and 2 M NaOH. Thecrude sulphonamide resulting from subsequent acidification of the reaction mixture wasisolated by filtration, washed well with water, and dried. Purification was carried out by flashcolumn chromatography (2% MeOH/CH2Cl2 as eluant), giving the title compound as a paleyellow solid (211 mg, 545).

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, 2,4-Difluorobenzene-1-sulfonyl chloride, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Spicer, Julie A.; Miller, Christian K.; O’Connor, Patrick D.; Jose, Jiney; Huttunen, Kristiina M.; Jaiswal, Jagdish K.; Denny, William A.; Akhlaghi, Hedieh; Browne, Kylie A.; Trapani, Joseph A.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 4; (2017); p. 1050 – 1054;,
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Chlorides – an overview | ScienceDirect Topics

102-49-8, name is 3,4-Dichlorobenzylamine, 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. Formula: C7H7Cl2N

Example 316 ethyl 4-[({[2-({[(3,4-dichlorophenyl)methyl]amino}carbonyl)-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl]methyl}oxy)methyl]benzoate A suspension of ethyl 5-{[({4-[(ethyloxy)carbonyl]phenyl}methyl)oxy]methyl}-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-2-carboxylate (0.400 g, 0.961 mmol) obtained in Reference Example 158 and 1-(3,4-dichlorophenyl)methanamine (0.287 g, 1.63 mmol) in ethanol (16 mL) was stirred with heating at 80° C. for 15 hrs. The mixture was allowed to cool to room temperature and the precipitated solid was collected by filtration and washed with ethanol to give the title compound as a white powder (475 mg, 91percent). melting point: 253-254° C.

The synthetic route of 102-49-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; Terauchi, Jun; Nara, Hiroshi; Oki, Hideyuki; Sato, Kenjiro; (166 pag.)US2015/329556; (2015); A1;,
Chloride – Wikipedia,
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Reference of 6940-78-9, A common heterocyclic compound, 6940-78-9, name is 1-Bromo-4-chlorobutane, molecular formula is C4H8BrCl, 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.

Compound (1) 7-hydroxy-2-quinolone (10.0 g, 62 mmol), 120 ml of ethanol and potassium carbonate (19.0 g, 138 mmol) were added in a 500ml reaction bottle .Compound (II) 1-bromo-4-chlorobutane (12.0 g, 70 mmol) was added with stirring, the temperature was raised to reflux and stirred for 2 hours. 100 ml of water and the compound (IV) 1-(benzo[b]thiophen-4-yl) piperazine hydrochloride (15.0 g, 59 mmol) were added, and the mixture was stirred under reflux for 9 hours. Part of the solvent was distilled off, cooled to 50 C, 40 ml of ethyl acetate was added and stirred for 0.5 hour, then continued to cooled down below 20 C, after filtration under reduced pressure, the filter cake was washed three times with 20 ml of ethanol, and then dried in a blast oven at 70 C for 3 hours. Brexpiprazole (Compound V) 14.5 g was obtained in a molar yield of 54%, which was substantially the same as the molar yield of 55% of the method described in Scheme 2.

The synthetic route of 6940-78-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hangzhou Xin Bosi Bio-pharmaceutical Co., Ltd.; Du Huanda; Ding Jiansheng; Ye Xinjie; Wang Zhenyu; Chen Yu; Wang Wanqing; Han Lu; Liu Yanhua; (8 pag.)CN105061414; (2019); B;,
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Adding a certain compound to certain chemical reactions, such as: 461432-23-5, name is 4-Bromo-1-chloro-2-(4-ethoxybenzyl)benzene, 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 461432-23-5, Formula: C15H14BrClO

To a solution of 4-bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene (10.0 g, 30.71 mmol) in dichloromethane (40.0 mL) cooled to 0 degrees Celsius under nitrogen was added drop- wise over 30 minutes a 1 M solution of boron trichloride in dichloromethane (34 mL, 34.0 mmol). After the addition was complete, the reaction was allowed to warm to room temperature overnight (-16 hours). The reaction mixture was cooled to 0 degrees Celsius and an aqueous solution of 1 N hydrochloric acid was added. The resulting mixture was stirred for 30 minutes and then extracted using dichloromethane. The organic layer was separated and the aqueous layer was extracted two times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The TLC showed only 50% conversion. The crude material was redissolved in dichloromethane (40 mL), cooled to 0 degrees Celsius, and a 1M solution of boron tribromide in dichloromethane (31 mL, 31 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature over the weekend (-55 hours). The reaction mixture was cooled to 0 degrees Celsius and an aqueous solution of 1 N hydrochloric acid was added dropwise. The resulting mixture was stirred for 30 minutes and then extracted usingdichloromethane. The organic layer was separated and the aqueous layer was extracted two times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The reaction was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (120 g silica gel column) and eluting with a gradient of 0 to 100% ethyl acetate in heptane. 9 g (98% yield) of the desired product obtained as a white solid.

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, 4-Bromo-1-chloro-2-(4-ethoxybenzyl)benzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PFIZER INC.; MASCITTI, Vincent; WO2011/51864; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 6579-54-0, name is 2,6-Dichlorobenzenesulfonyl 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. Computed Properties of C6H3Cl3O2S

General procedure: To a mixture of corresponding 7 (150mg, 0.4mmol) in anhydrous THF (15mL) and DMF(3mL), corresponding sulfonyl chloride (0.5mmol) was added slowly at 0C and stirred at room temperature overnight. The mixture was poured into water and extracted with ethyl acetate (50mL×3). The combined organic layer was washed by saturated sodium chloride solution (40mL×3) and concentrated. The residue was purified by silica gel chromatography to afford 8a-8i.

The synthetic route of 2,6-Dichlorobenzenesulfonyl chloride has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Li; Zhang, Beichen; Zhao, Jingyun; Zhi, Yanle; Wang, Lu; Lu, Tao; Chen, Yadong; European Journal of Medicinal Chemistry; vol. 138; (2017); p. 942 – 951;,
Chloride – Wikipedia,
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