Month: November 2020

933190-51-3, name is 8-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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. 933190-51-3

A mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (300 mg, 1.3 mmol), (S)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (252 mg, 1.42 mmol), Pd2(dba)3 (75 mg, 0.13 mmol), BINAP (324 mg, 0.52 mmol), Cs2CO3 (1272 mg, 3.9 mmol) and dioxane (20 mL) was heated to 100 C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give (S)-6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (124 mg, 29%) as a yellow solid. LC-MS: [M+H]+, 329.0, tR=1.951 min.

Statistics shows that 933190-51-3 is playing an increasingly important role. we look forward to future research findings about 8-Bromo-6-chloroimidazo[1,2-b]pyridazine.

Reference:
Patent; Hoffmann-La Roche Inc.; Hermann, Johannes Cornelius; Kuglstatter, Andreas; Lucas, Matthew C.; Padilla, Fernando; Wanner, Jutta; Zhang, Xiaohu; US2013/109661; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

A common heterocyclic compound, 33863-76-2, name is 1-Bromo-3-chloro-5-fluorobenzene, molecular formula is C6H3BrClF, 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. 33863-76-2.

EXAMPLE 8.0 8-(1-(3-chloro-5-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (single enantiomer) To a mixture of 8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (350 mg, 1.01 mmol, single enantiomer, [alpha]D20: +35 in acetonitrile), cesium carbonate (1288 mg, 3.95 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (147 mg, 0.25 mmol) and 1-bromo-3-chloro-5-fluorobenzene (467 mg, 2.23 mmol) in degassed 1,4-dioxane (2 ml), was added tris(dibenzylideneacetone)dipalladium (70 mg, 0.08 mmol). The suspension was heated in a sealed container at 95 C. for 16 hrs. The reaction mixture was filtered through a short pad of dicalite and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 0 to 8% isopropanol in DCM. The solvent was evaporated to dryness, the product triturated with diethyl ether-DCM (9:1), collected by filtration and dried to afford 8-(1-(3-chloro-5-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (320 mg; 67%) as a clear yellow solid. Mass Spectrum: M+H+ 474. [alpha]D20: -138. NMR Spectrum (DMSOd6): 1.52 (d, 3H), 2.75 (bs, 3H), 2.95 (bs, 3H), 3.49-3.63 (m, 4H), 3.70-3.79 (m, 4H), 4.98-5.07 (m, 1H), 5.60 (s, 1H), 6.23 (d, 1H), 6.42 (d, 1H), 6.43 (ddd, 1H), 6.94 (d, 1H), 7.54 (d, 1H), 7.80 (d, 1H).

The synthetic route of 1-Bromo-3-chloro-5-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; US2011/98271; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2533-69-9, 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. 2533-69-9 name is Methyl 2,2,2-trichloroacetimidate, 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.

Step D4-bromo- 6-cyclopropyl-2-(trichlorom ethyl)- 1 H-benz imidazole[00176] A suspension of (2-amino-3-bromo-5-cyclopropylphenyl)amine (11 .16 g, 42.3 mmol) in acetic acid (123 ml) followed by the drop-wise addition of methyl 2,2,2- trichloroethanimidoate (6.42 ml, 50.8 mmol). The mixture was stirred at room temperature overnight. The suspension was treated by additional methyl 2,2,2,-trichloroethanimidoate (3.0 mL) and stirred for 2 hours. The mixture was diluted with Et20 and treated with water and the layers were separated. The aqueous layer was extracted with Et20 (3x) and then the combined organic phase was washed with water (2 x), brine (2x), dried Na2S04, filtered, and concentrated. The residue was co-evaporated with toluene (2x) to give a brownish-black residue. The residue was triturated with Et20 and then solids were filtered and discarded. The filtrate was concentrated and then co-evaporated from toluene (2x) to give the title compound (8.44 g, 46.7%). ES-LCMS: 355.0, 357.0 (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; GLAXOSMITHKLINE LLC; BANKA, Anna; CATALANO, John G; FANG, Jing; PEAT, Andrew James; TAI, Vincent; TURNER, Elizabeth; WO2011/97491; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

15205-15-9, These common heterocyclic compound, 15205-15-9, name is 2-Chloro-6-fluorobenzylamine, 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.

Step 1: (S) -tert-Butyl (1- (4- ( (2-chloro-6-fluorobenzyl) carbamoyl) -2- (3-ethoxy-4-methoxyphenyl) oxazol-5-yl) ethyl) carbamate[0639]To 10 mL of dichloromethane were added (S) -5- (1- ( (tert-butoxycarbonyl) amino) ethyl) -2- (3-ethoxy-4-methoxyphenyl) oxazole-4-carboxylic acid (0.3 g, 0.74 mmol) , 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (212 mg, 1.11 mmol) and 1-hydroxy-7-azabenzotriazole (151 mg, 1.11 mmol) , and the mixture was stirred at 0 for 30 minutes. To the mixture were added dropwise (2-fluoro-6-chlorophenyl) methanamine (0.11 mL, 0.89 mmol) and N, N-diisopropylethylamine (0.39 mL, 2.21 mmol) in turn, and the resulting mixture was stirred at rt for 12 hours. The reaction mixture was washed with water (10 mL ¡Á 3) , and the organic layer was dried over anhydrous sodium sulfate. The organic solvent was removed and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) 6/1) to give the title compound as a white solid (190 mg, 47) .[0640]1H NMR (400 MHz, CDCl3) : delta ppm 7.60 (dd, J1 8.4 Hz, J2 1.9 Hz, 1H) , 7.52 (d, J 1.8 Hz, 1H) , 7.39 -7.29 (m, 1H ) , 7.27 -7.25 (m, 1H) , 7.10 -7.05 (m, 1H) , 6.94 (d, J 8.5 Hz, 1H) , 5.30 -5.25 (m, 1H) , 4.91 -4.84 (m, 2H) , 4.23 -4.18 (m, 2H) , 3.95 (s, 1H) , 1.57 -1.51 (m, 6H) , 1.45 (s, 9H) and MS-ESI: m/z 549.2 [M+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 15205-15-9.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; LIU, Bing; YU, Tianzhu; ZHANG, Yingjun; ZHANG, Xiangyu; ZHANG, Shiguo; CHENG, Changchung; ZHANG, Jiancun; WO2015/161830; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

39885-50-2, A common compound: 39885-50-2, name is 2-Chloro-4-(trifluoromethyl)aniline, belongs to chlorides-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

(b) raney Nickel (0.7 g) was added to a solution of the above isomer mixture (35.85 g) in ethanol in a hydrogenation reactor at 50¡ã C. under hydrogen at 5 bar for 5 hours.. The mixture was cooled, filtered and evaporated to give a 95/5 mixture of 2-chloro-4-trifluoromethylaniline and 2-chloro-5-trifluoromethylaniline (33.1 g).. hydrogen chloride gas was added over 0.5 hour to a solution of the above mixture in ethanol and chlorobenzene, cooled to 0¡ã C., and filtered to give 2-chloro-4-trifluoromethylaniline hydrochloride (33.5 g), having a purity of >99percent.. The overall yield from 3,4-dichlorobenzotrifluoride was 85percent.

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-Chloro-4-(trifluoromethyl)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Aventis CropScience, S.A.; US6410737; (2002); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

13745-86-3, Name is 11-Chlorodibenzo[b,f][1,4]thiazepine, 13745-86-3, 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.

21.6 g of 11-chloro-dibenzo [b, f] [l, 4] thiazepine was dissolved in 120 ml of xylene, stirred and 5.0 gPiperazine, 1.2 g of potassium iodide and 24 g of potassium carbonate were added and the reaction temperature was controlled to 105 to 115 C and kept at the same temperature for 5 hours. Insulation finishedBi to 20 ~ 30 C, add 100ml of purified water washing and stirring for 20 minutes, and then suction filtration. The filtered solid was re-added100ml purified water was beaten and the obtained product was filtered and purified. The purity was 99.5% and the yield was 88.0%.

Statistics shows that 11-Chlorodibenzo[b,f][1,4]thiazepine is playing an increasingly important role. we look forward to future research findings about 13745-86-3.

Reference:
Patent; Qilu Tianhe Pharmaceutical Co., Ltd.; Zhang, Wenwen; Guan, Qinghua; Zhang, Xiaoyong; Fan, Changying; Li, Baoyong; Wu, Ke; Zhang, Zhaozhen; Dong, Tinghua; Du, Yunfeng; (5 pag.)CN104447616; (2016); B;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

202197-26-0, A common heterocyclic compound, 202197-26-0, name is 3-Chloro-4-((3-fluorobenzyl)oxy)aniline, molecular formula is C13H11ClFNO, 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.

A 100-ml three-necked round bottom flask was charged with 15 ml of water, At 0 deg C (0.45 g, 1.81 mmol) 3-chloro-4- (3-fluorobenzyloxy)aniline and NaNO2 (0.25 g, 3.62 mmol) were successively added with stirring, HCl (0.19 g, 5.42 mmol) was added dropwise, Speed can not be too fast, After completion of the dropwise addition, The temperature of the reaction system was maintained at 0-5 deg C for 1.5 h. The color of the reaction liquid was deepened. An aqueous solution of NaN3 (0.14 g, 2.17 mmol) was then added, Must be added and the speed can not be too fast, During the addition, a large amount of foam is generated, Reaction solvent water is added at this time. After completion of the addition, the reaction was continued for 3 h while the temperature was kept constant, and the progress of the reaction was monitored by TLC during the reaction. During the course of the reaction, the color of the reaction solution was found to change from dark yellow to light yellow with yellow foam. At the end of the reaction, The reaction solution was extracted with EA (3 * 40 ml)The organic phase was washed with brine (3 * 10 ml) The organic phases were combined, Mg2SO4 concentrate, Purification by silica gel column chromatography gave 0.48 g (yield: 95.05%) of a yellow solid.

The synthetic route of 202197-26-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Tianjin International Joint Academy of Biotechnology & Medicine; Chen, Yue; Rao, Zihe; Yang, Cheng; Bai, Cuigai; Zhang, Wei; Pan, Chengwen; Meng, Fanfei; Wang, Song; (11 pag.)CN103159748; (2016); B;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 64628-73-5, name is 3-Chloro-4-(trifluoromethoxy)aniline, I believe this compound will play a more active role in future production and life. 64628-73-5

General procedure: A dry, 50 mL round bottom flask was charged with a magnetic stir bar then sealed with a septum and flushed with nitrogen. To this was added the salicylic acid derivative (2.0 mmol) and dichloromethane (10 mL). While stirring, SOCl2 (10 mmol) was added dropwise, followed by dimethylformamide (0.05 mmol), and the mixture was allowed to stir at room temperature under nitrogen for 12 hours. At this point, the mixture was concentrated under vacuum to afford the solid acid chloride derivative which was used immediately without further purification. The flask containing the acid chloride was then re-sealed with a septum and placed under a nitrogen atmosphere, and its contents were re-suspended in fresh dichloromethane (20 mL). While stirring, the aniline derivative (4.0 mmol) was added and the resulting opaque mixture was stirred for an additional 18 h. At this point, the mixture was quenched with ice water (5 mL) and phases were separated using a separatory funnel. The aqueous layer was extracted twice with dichloromethane (20 mL) then the organic layers were combined and washed with brine (40 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated under vacuum to afford a crude solid residue. This residue was then re-suspended in dichloromethane (10 mL) and adsorbed onto silica gel (1 g), then chromatographed on a 12 g silica gel column using a solvent gradient of 0-40% ethyl acetate in hexanes over 25 min. The product-containing fractions were combined then concentrated under vacuum to afford the purified salicylamide derivative.

The chemical industry reduces the impact on the environment during synthesis 64628-73-5. I believe this compound will play a more active role in future production and life.

Reference:
Article; Chae, Hee-Don; Cox, Nick; Capolicchio, Samanta; Lee, Jae Wook; Horikoshi; Kam, Sharon; Ng, Andrew A.; Edwards, Jeffrey; Butler, Tae-Leon; Chan, Justin; Lee, Yvonne; Potter, Garrett; Capece, Mark C.; Liu, Corey W.; Wakatsuki, Soichi; Smith, Mark; Sakamoto, Kathleen M.; Bioorganic and Medicinal Chemistry Letters; vol. 29; 16; (2019); p. 2307 – 2315;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

627-42-9, name is 2-Methoxyethyl chloride, 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. 627-42-9

A mixed solution of 1500 g of 1-naphthol, 1032 g of 2-methoxyethyl chloride, 460 g of sodium hydroxide, 78 g of sodium iodide and 3000 g of ethanol was heated and stirred at 80 C for 37 hours under a nitrogen atmosphere.After cooling, 3000 g of water and 5000 g of toluene were added to separate the organic layer, and the mixture was washed five times with 1800 g of a 5 mass% aqueous sodium hydroxide solution. Subsequently, the solution was washed four times with 1800 g of water, and then the organic layer was concentrated to obtain 1835 g of an oily product. This was distilled under reduced pressure (110 C / 13 Pa) to obtain 1637 g (yield: 77%) of the target compound

Statistics shows that 627-42-9 is playing an increasingly important role. we look forward to future research findings about 2-Methoxyethyl chloride.

Reference:
Patent; Shin-Etsu Chemical Industry Co., Ltd.; Ohashi, Masaki; Kobayashi, Tomohiro; Seki, Akihiro; Sagehasi, Masayoshi; Fukushima, Masahiro; (42 pag.)KR101695054; (2017); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

29671-92-9, Name is Carbamimidic chloride hydrochloride, 29671-92-9, 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.

Example 320 Synthesis of 2-amino-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one A mixture of ethyl 2-amino-5-(4-fluorophenyl)thiophene-3-carboxylate (0.3 g, 1.13 mmol), chloroformamidine hydrochloride (0.33 g, 2.83 mmol) and dimethylsulfone (0.53 g, 5.65 mmol) was heated at 120-130 C. for 30 minutes. After cooling down to room temperature, water (10 ml) was added and ammonium hydroxide was used to neutralize the suspension. The solid was filtered off, washed with water and dried. The crude residue was purified by flash chromatography on silica gel (CH2Cl2/MeOH 10:1) to yield the title compound as a white solid (0.28 g, 95%). 1H NMR (300 MHz, DMSO, 25 C.): delta=11.05 (s, 1H, NH), 7.66-7.71 (m, 2H, PhH), 7.51 (s, 1H, CH), 7.23 (t, J=8.8 Hz, PhH), 6.73 (s, 2H, NH2) ppm. HRMS: calcd for C12H9FN3OS 262.04504, found 262.04413.

Statistics shows that Carbamimidic chloride hydrochloride is playing an increasingly important role. we look forward to future research findings about 29671-92-9.

Reference:
Patent; KATHOLIEKE UNIVERSITEIT LEUVEN, K.U.LEUVEN R&D; De Jonghe, Steven; Gao, Ling-Jie; Herdewijn, Piet; Herman, Jean; Jang, Miyeon; Leyssen, Pieter; Louat, Thierry; Neyts, Johan; Pannecouque, Christophe; Vanderhoydonck, Bart; US2013/190297; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics