Month: May 2021

Electric Literature of 501-29-1, 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 501-29-1 as follows.

A mixture of 4-chloro-3-fluoroanisole (2.52 g, 15.7 mmol, 1.0 eq.), silver trifluoroacetate (8.57 g, 38.8 mmol, 2.5 eq.), iodine (7.95 g, 31.3 mmol, 2.0 eq.) and chloroform (100 mL) is stirred at r.t. for 16h. The reaction mixture is filtered through a silica plug on a fritted funnel and rinsed with chloroform. The filtrate is washed successively with an aqueous solution of Na2S2O3, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica gel to afford the expected product

According to the analysis of related databases, 501-29-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GALAPAGOS NV; LES LABORATOIRES SERVIER; LABEGUERE, Frederic, Gilbert; HENG, Rama; DE CEUNINCK, Frederic, Andre; ALVEY, Luke, Jonathan; AMANTINI, David; BREBION, Franck, Laurent; DEPREZ, Pierre, Marc, Marie, Joseph; GOSMINI, Romain, Luc, Marie; JARY, Helene; PEIXOTO, Christophe; POP-BOTEZ, Iuliana, Ecaterina; VARIN, Marie, Laurence, Claire; (180 pag.)WO2017/211666; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 10061-02-6, 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 10061-02-6 as follows.

A reactor was charged with 1.0 kg (9.0 mol) of trans-1, 3-dicloropropene, 3 L of acetonitrile and 1.02 kg (10 mol) of sodium bromide. The suspension was heated to reflux for at least 24 hours, then cooled to 20/250C at the end of the reaction; the salts were filtered and washed with 2 x 500 mL of acetonitrile. The filtrate was distilled through a Vigreux column at atmospheric pressure and internal temperature of 80/l00C to remove the acetonitrile, getting 1.096 kg of a dark orange oil. Weight composition by 1H-NMR: 89% of trans-3-bromo-l- chloropropene, 8% of trans-1, 3 -dicloropropene and 3% of solvent. 1H NMR (CDC13) delta: 3.93 (m, 2H, CH2), 6.14 (m, IH, CH), 6.33 (dt, IH, CHCl). MS (EI) m/z: 156 (M+), 77.

According to the analysis of related databases, 10061-02-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F.I.S. FABBRICA ITALIANA SINTETICI S.p.A; WO2008/6394; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 39989-43-0, name is 3,5-Dichlorobenzylamine belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of 3,5-Dichlorobenzylamine

Example 28 – Synthesis of Compound 24 (S)-9-fluorenylmethyl 10-(3,5-dichlorobenzyl)- 2,2-dimethyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-triazaiscos-19-en-8-ylcarbamate24(lSr)-9-fluorenylmethyl 10-(3,5-dichlorobenzyl)-2,2-dimethyl- 4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-triazaiscos-19-en-8- ylcarbamateTo 3,5-dichlorobenzylamine (0.49 g, 2.8 mmol) in DCM (5 ml_) was added the alpha,beta- unsaturated ketone 23 (2.12 mmol) in DCM (10 ml_). After stirring at room temperature for 15 mins, Fmoc-diaminobutyric acid(Boc)-OH (1.35 g, 3.1 mmol) and DIC (0.5 ml_, 3.2 mmol) was added. The reaction was stirred at room temperature overnight. The DCM was removed by rotary evaporation and the residue was subjected to column chromatography on silica gel using petroleum spirit:EtOAc (1 :1 to 0:1 ), providing compound 24 (0.48 g, 22%).

The synthetic route of 39989-43-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MIMETICA PTY LTD; BLASKOVICH, Mark, Arnold, Thomas; CASSIDY, Peter, Joseph; WO2010/96853; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 461432-23-5,Some common heterocyclic compound, 461432-23-5, name is 4-Bromo-1-chloro-2-(4-ethoxybenzyl)benzene, molecular formula is C15H14BrClO, 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 nitrogen protection, in a 250 ml three-necked flask (numbered bottle A) was added 5-bromo-2-chloro-4′-ethoxydiphenylmethane (III-1) (12.5, 0.038 mol), 40 ml of dry tetrahydrofuran. And 80 ml of toluene (dried by chlorination of hydrazine), and the dried ice acetone was cooled to -72 C with stirring, and a 2.5 Mu n-BuLi n-hexane solution (18.4 ml, 0.046 mol) was added dropwise to ensure that the temperature was not higher than -60 C, stir for 30 min. Prepare a 500ml three-neck bottle (No. B), nitrogen protection, add 2,3,4,6-tetra-O-trimethylsilyl-FD-gluconolactone (19.7g, 0.042mol) and 110ml toluene (dried by chlorination of hydrazine), dry ice acetone was cooled to -72V. After the reaction time in the bottle A was reached, the solution in the bottle A was introduced into the bottle B, the reaction was continued for 2 hours at a low temperature, methanesulfonic acid (14.8 g, 0.154 mol) and 110 ml of methanol were added, and the dry ice bath was removed, and the temperature was naturally raised to room temperature. The reaction was overnight. After completion of the reaction, a saturated sodium hydrogencarbonate solution was added to adjust the pH to neutrality. After separation, the aqueous phase was extracted with ethyl acetate. The organic phase was washed once with saturated sodium chloride and dried over anhydrous sodium sulfate. After suction filtration, the solvent was evaporated, and after chromatography, 10.8 g (64.3%) of white foam solids were obtained.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Bromo-1-chloro-2-(4-ethoxybenzyl)benzene, its application will become more common.

Reference:
Patent; Huarun Shuang He Pharmaceutical Co., Ltd.; Zhai Jianguo; He Yang; Zhu Yingjie; Zhou Yisui; Ma Hongmin; Song Meng; (46 pag.)CN108218928; (2018); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 51114-68-2, 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. 51114-68-2, name is 3-Chloro-2-methoxyaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

(3-Chloro-2-methoxy-phenyl)-thiourea To a solution of 3-chloro-2-methoxy-phenylamine (2.36 g, 15.0 mmol, Aldrich) in acetone (30 mL) at reflux was slowly added benzoyl isothiocyanate (2.22 mL, 16.5 mmol) and the mixture was stirred at reflux for 30 min, then was poured into a mixture of ice and water. The precipitate was collected by vacuum filtration and was treated with 10% aq. NaOH (15 mL). The mixture was heated to reflux for 40 min, and was cooled to room temperature. A white solid precipitated and was collected by vacuum filtration, affording the crude title compound which was used without further purification.

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, 3-Chloro-2-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JACKSON, Paul Francis; Manthey, Carl; Rhodes, Kenneth; Scannevin, Robert; Leonard, Kristi Anne; Barbay, Joseph Kent; Todd, Matthew; Springer, Barry A.; US2012/302573; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 19752-55-7, name is 1-Bromo-3,5-dichlorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Safety of 1-Bromo-3,5-dichlorobenzene

General procedure: A solution of aryl bromide (0.3 mol) (see Table 1) in diethyl ether (~215 mL) was added to a mixture of Mg turnings (7.29 g, 0.3 mol), diethyl ether (~17 mL), and a catalyst (several iodine crystals) under argon with stirring at such a rate that the ether was boiling, then the mixture was refluxed for 1?1.5 h. Since 1-bromo-2,4-dichlorobenzene (the starting compound for the synthesis of a-hydroxy ester 3e) did not react with magnesium under these conditions, the Grignard reaction for it was carried out in the presence of a large amount of iodine and dibromoethane (4 mL) upon reflux for 2.5 h.

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 19752-55-7.

Reference:
Article; Vasilyeva; Vorobyeva; Russian Chemical Bulletin; vol. 67; 8; (2018); p. 1426 – 1432; Izv. Akad. Nauk, Ser. Khim.; 8; (2018); p. 1426 – 1432,7;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 39191-07-6, name is 1-(3-Chlorophenyl)-N-methylmethanamine, 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. Quality Control of 1-(3-Chlorophenyl)-N-methylmethanamine

Diisopropylethylamine (0.073 mL, 0.42 mmol) was added to a mixture of 3-[(2-methoxy-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonyl)-amino]-4-methyl-benzoic acid (0.05 g, 0.14 mmol) (from Example 20 supra) and HATU (0.080 g, 0.21 mmol) (Aldrich) in DMF (2.0 mL). The resulting mixture was stirred at room temperature for 30 minutes. 3-Chloro-N-methylbenzylamine (0.061 mL, 0.42 mmol) (Aldrich) was added. The mixture was stirred for 18 hours. The mixture was partitioned between ethyl acetate and water. The precipitate formed was collected by filtration and washed with methanol and dried in vacuum oven to give 2-methoxy-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid {5-[(3-chloro-benzyl)-methyl-carbamoyl]-2-methyl-phenyl}-amide. (Yield 0.018 g, 26.1%).HR-MS (ES+) m/z Calculated for C25H23ClN5O4 ([M+H]+): 514.1252. Found: 514.1251.

The synthetic route of 1-(3-Chlorophenyl)-N-methylmethanamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Anderson, Kevin; Chen, Yi; Chen, Zhi; Luk, Kin-Chun; Rossman, Pamela Loreen; Sun, Hongmao; Wovkulich, Peter Michael; US2012/184542; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 27139-97-5,Some common heterocyclic compound, 27139-97-5, name is 2-Bromo-4-chloro-1-methylbenzene, molecular formula is C7H6BrCl, 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.

5-Chloro-2-methylbenzaldehyde Into a flame-dried 250 mL round-bottom flask equipped with a magnetic stir bar and under N2 was added 2-bromo-4-chlorotoluene (10.0 mL, 75.0 mmol) in anhydrous THF (150 mL). The clear sol. was cooled to -78° C. and BuLi (36.6 mL, 82.4 mmol, 2.25 M sol. in hexanes) was added dropwise over 20 min. The resulting light orange sol. was stirred at -78° C. for 1 h, and DMF (30 mL, 375 mmol) was added in a single addition. The resulting mixture was allowed to warm to rt over 4 h. The reaction was quenched by addition of aq. 1M HCl (20 mL), and stirred at rt overnight. The reaction mixture was poured into a 500 mL separatory funnel containing aq. 1M HCl (200 mL). The mixture was extracted with Et2O (3*100 mL). The combined org. layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to a yellow oil. Purification by short-path distillation under reduced pressure (1 mm Hg) yielded the title compound as a light yellow oil (7.99 g, 69percent). bp=70-72° C. at 1 mm Hg. 1H NMR (CDCl3, 500 MHz) delta 10.23 (1H, s), 7.77 (1H, d, J=2.5 Hz), 7.45 (1H, dd, J=8.0, 2.5 Hz), 7.22 (1H, d, J=8.0 Hz), 2.65 (3H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-4-chloro-1-methylbenzene, its application will become more common.

Reference:
Patent; Bezencon, Olivier; Bur, Daniel; Corminboeuf, Olivier; Dube, Daniel; Grisostomi, Corinna; MacDonald, Dwight; McKay, Dan; Powell, David; Remen, Lubos; Richard-Bildstein, Sylvia; Scheigetz, John; Therien, Michel; Weller, Thomas; US2009/176823; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 29671-92-9, 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. 29671-92-9, name is Carbamimidic chloride hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

Chloroformamidine hydrochloride with Sodium hydroxide is put into A 25 mL round bottom flask was charged with 3 mL of acetonitrile solvent and pretreated Neutralize the acid, get free amidine. Then, ethyl benzoylacetate and perfluoroiodobutane were successively added at room temperature. indoor Light and room temperature for 8h, TLC monitoring reaction end, stop the reaction, the mixture. [0119] Ethyl benzoylacetate: Perfluorooiodobutane: Chloroformamidine hydrochloride: Sodium hydroxide = 1.0: 1.1: 1.1: 4.1; [0120] 2. The mixture was extracted three times with water, the organic phases were combined and the organic solvent was removed by distillation under reduced pressure to give crude product. [0121] 3. The crude product was chromatographed on silica gel eluting with eluent (petroleum ether: ethyl acetate = 30: 1 (nu: nu) A white solid was obtained as the product ethyl-2-chloro-4-perfluoropropyl-6-phenylpyrimidine-5-carboxylate in 57% yield.

The chemical industry reduces the impact on the environment during synthesis Carbamimidic chloride hydrochloride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Liaoning University; Liang Fushun; Wang Rui; Han Zhengbo; Su Zhongmin; (12 pag.)CN106831603; (2017); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 918538-05-3, 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. 918538-05-3 name is 2,4-Dichloropyrrolo[2,1-f][1,2,4]triazine, 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.

General procedure: A slurry of (2-chloro-4-(1-(3,4,5-trimethoxyphenyl)-lH-imidazol-4-ylamino)pyrrolo[1,2- f][1,2,4]triazin-7-yl)methanol (101b) (97 mg, 0.23 mmol), (S)-pyrrolidin-2-ylmethanol (171 mg, 1.69 mmol), di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (di-t-Bu-XPhos, 14 mg, 0.034 mmol), Pd2(dba)3 (14 mg, 0.016 mmol), sodium tert-butoxide (162 mg, 1.69 mmol) in PhMe (5 mL) was degassed and placed in a sealed reactor. The reaction was heated at 100 C for 48 hr, cooled to room temperature, quenched with saturated aqueous H4CI and extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, washed with water, brine, dried, filtered and concentrated in vacuum to dryness. The residue obtained was purified by flash column chromatography (Silica gel 12 g, eluting with MeOH in DCM from 0 to 40%) to afford (S)-(l-(7-(hydroxymethyl)-4-(l-(3,4,5-trimethoxyphenyl)-lH-imidazol-4- ylamino)pyrrolo[l,2-f][l,2,4]triazin-2-yl)pyrrolidin-2-yl)methanol (101c) (12 mg, 11 % yield) as a white solid; MR (300 MHz, DMSO-^e) delta 10.47 (s, 1H, D20 exchangeable), 8.24 (d, J = 1.5 Hz, 1H), 7.97 (s, 1H), 7.10 (d, J= 4.4 Hz, 1H), 6.96 (s, 2H), 6.37 (d, J = 4.4 Hz, 1H), 4.67 (s, 2H), 4.32 – 4.09 (m, 1H), 3.88 (s, 6H), 3.79 – 3.70 (m, 1H), 3.68 (s, 3H), 3.67 – 3.52 (m, 1H), 3.53 – 3.20 (m, 2H), 2.14 – 1.75 (m, 4H); MS (ES+): 496.5 (M+l), 518.5 (M+Na); MS (ES-): 494.4 (M-l).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2,4-Dichloropyrrolo[2,1-f][1,2,4]triazine, and friends who are interested can also refer to it.

Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; KOTIAN, Pravin, L.; BABU, Yarlagadda, S.; KUMAR, V., Satish; ZHANG, Weihe; LU, Peng-Cheng; RAMAN, Krishnan; (747 pag.)WO2018/232094; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics