Category: chlorides-buliding-blocks

These common heterocyclic compound, 64628-73-5, name is 3-Chloro-4-(trifluoromethoxy)aniline, 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. COA of Formula: C7H5ClF3NO

4-Bromo-7-fluoro-1H-indole-2-carboxylic acid ethyl ester (200 mg, 0.7 mmol) was dissolved in toluene (16 mL), and Pd2 (dba) 3 (64 mg, 0.07 mmol) and Davephos (55 mg , 0.14 mmol) and K3PO4 (446 mg, 2.1 mmol, 2.1 mL H2O), after stirring well, 3-chloro-4-trifluoromethoxyaniline (444 mg, 2.10 mmol) in toluene (4 mL) was added, protected by argon Then, the reaction was refluxed overnight, and a small amount of starting material remained. Cool to room temperature, concentrate, add EA (30mL) to dissolve the residue, 6N hydrochloric acid (10mL × 2), saturated brine (20mL × 3), water (20mL × 2), column chromatography (P / E = 20: 1 ~ 10: 1) to obtain 158 mg of a white solid with a yield of 54.3% and a melting point: 143-145 C.

The synthetic route of 3-Chloro-4-(trifluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chinese Academy Of Medical Sciences Pharmaceutical Institute; Xu Boling; Chen Xiaoguang; Cui Guonan; Lai Fangfang; Zhou Jie; Ji Ming; Wang Xiaoyu; Du Tingting; Li Ling; Jin Jing; (144 pag.)CN110483366; (2019); A;,
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Reference of 67279-24-7, 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. 67279-24-7, name is 1,4-Dichloro-5,6,7,8-tetrahydrophthalazine, This compound has unique chemical properties. The synthetic route is as follows.

EXAMPLE 41; Synthesis of 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine; A slurry of 1,4-dichloro-5,6,7,8-tetrahydrophthalazine (1.66 g, 8.18 mmol) and 4-(2-(4-aminophenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine (2.00 g, 6.82 mmol) in 14 mL 2-BuOH was heated in a sealed pressure vessel to 110 C. The reaction became a thick mass that eventually became a stirring suspension over about 30 min. After 4 h, the reaction was cooled to ambient temperature, and the material was partitioned between 2N NaOH and EtOAc. The aqueous layer was extracted once with EtOAc. The organic layers were dried over anhyd. sodium sulfate, filtered, and concentrated to yield a brown solid. This solid was dissolved in MeOH/MC and adsorbed onto 10 g silica gel, dried, and purified by chromatography (0-100% EtOAc/DCM) to give 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-5,6,7,8-tetrahydrophthalazin-1-amine as an off-white solid. MS m/z=460 [M+H]+. Calc’d for C24H22ClN7O: 459.9.

The chemical industry reduces the impact on the environment during synthesis 1,4-Dichloro-5,6,7,8-tetrahydrophthalazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Cee, Victor J.; Deak, Holly L.; Du, Bingfan; Geuns-Meyer, Stephanie D.; Hodous, Brian L.; Nguyen, Hanh Nho; Olivieri, Philip R.; Patel, Vinod F.; Romero, Karina; Schenkel, Laurie; US2007/185111; (2007); A1;,
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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. 15205-11-5, name is 2-Chloro-4-fluorobenzylamine, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Chloro-4-fluorobenzylamine

theta-Oxo-1 -(phenylmethyl^-piperidinecarboxylic acid (0.117 g, 0.5 mmol, prepared as described below) was suspended in dichloromethane (5 ml) and treated with N-(3- dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (0.144 g, 0.75 mmol) and 1-hydroxybenzotriazole (0.102 g, 0.75 mmol). The mixture was stirred at room temperature for 15 minutes and then [(2-chloro-4-fluorophenyl)methyl]amine (0.096 g, 0.6 mmol) was added to the mixture and stirring at room temperature was continued for a further 48 hrs. The mixture was concentrated and partitioned between ethyl acetate and water. The ethyl acetate layer was separated and washed sequentially with 3N aqueous citric acid, water, saturated aqueous sodium hydrogen carbonate, water, and brine and then dried over anhydrous sodium sulphate. Concentration of the organic layer gave an oil which was purified by automated flash silica-gel column chromatography (Biotage SP4), eluting with a gradient of 0-100% ethyl acetate in hexane, to give lambda/-[(2-chloro-4- fluorophenyl)methyl]-6-oxo-1-(phenylmethyl)-2-piperidinecarboxamide (0.1 13 g) as an oil. LC/MS [M+H]+ = 375/377, retention time = 2.63 minutes.

The synthetic route of 15205-11-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/116845; (2008); A1;,
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Synthetic Route of 2533-69-9,Some common heterocyclic compound, 2533-69-9, name is Methyl 2,2,2-trichloroacetimidate, molecular formula is C3H4Cl3NO, 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 4-fluorobenzene-1,2-diamine [Aldrich, 653586] (0.03 g, 0.2 mmol) in acetic acid (1 mL) was added methyl 2,2,2-trichloroethanimidoate [Acros, AC16093-0250] (0.030 mL, 0.24 mmol) dropwise at room temperature. The mixture was stirred at room temperature for 2 h and poured into water (25 mL). The precipitate was separated by filtration and air-dried, which was directly used in the next step without purification.

The synthetic route of 2533-69-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Incyte Corporation; Zou, Ge; Combs, Andrew P.; Buesking, Andrew W.; (62 pag.)US2016/229843; (2016); A1;,
Chloride – Wikipedia,
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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. 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H3BrClF

A solution of 250 mg (0.686 mmol) (R)-tert-butyl 4-benzyl-2-((S)-2-hydroxy-3- methoxypropyl)piperazine-l -carboxylate and 0.1 ml 2-bromo-4-chloro-l-fluorobenzene (1.2 eq.) in DMSO (5 ml) under nitrogen atmosphere was stirred at room temperature for 2 h. The reaction mixture was poured onto brine and extracted twice with EtOAc. Combined extracts were washed with water three times and with saturated sodium chloride solution, dried over MgS04 and evaporated to dryness. The residue was purified by flash chromatography on silica with dichloromethane/methanol. (R)-tert- butyl 4-benzyl-2-((S)-2-(2-bromo-4-chlorophenoxy)-3-methoxypropyl)piperazine- 1 – carboxylate was obtained as oil (192 mg, 51 %).

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; ABBVIE DEUTSCHLAND GMBH & CO. KG; BACKFISCH, Gisela; BAKKER, Margaretha Henrica Maria; BLAICH, Guenter; BRAJE, Wilfried; DRESCHER, Karla; ERHARD, Thomas; HAUPT, Andreas; HOFT, Carolin; LAKICS, Viktor; MACK, Helmut; OELLIEN, Frank; PETER, Raimund; RELO, Ana Lucia; (141 pag.)WO2017/89458; (2017); A1;,
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Some common heterocyclic compound, 17318-08-0, name is 5-Bromo-1,3-dichloro-2-fluorobenzene, molecular formula is C6H2BrCl2F, 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. category: chlorides-buliding-blocks

To an oven dried 8 mL vial with teflon cap purged with N2 was added Zinc dust (298 mg, 4.56 mmol), DMF(1.5 mL), and iodine (57.8 mg, 0.228 mmol). To this mixture was added (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (500 mg, 1.519 mmol), immediately followed by iodine (57.8 mg, 0.228 mmol).Pd2(dba)3 (69.6 mg, 0.076 mmol), 2-dicyclohexylphosphino-2?,6?-dimethoxybiphenyl (62.4 mg, 0.152mmol), 5-bromo-1,3-dichloro-2-fluorobenzene (556 mg, 2.279 mmol) and the reaction mixture was allowedto stir at rt for 16 h. The crude mixture was diluted in 30 mL of EtOAc and DMF was removed using fouraqueous washes. The organic phase was dried over anhydrous sodium sulfate. The solution was filtered andconcentrated and the crude product was purified by silica gel chromatography using 100% hexanes to 30%EtOAc/Hexanes. The desired product was obtained as a pale yellow oil, (S)-methyl 2-((tertbutoxycarbonyl)amino)-3-(3,5-dichloro-4-fluorophenyl)propanoate, 0.102 g which was taken into next stepdirectly.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 17318-08-0, its application will become more common.

Reference:
Patent; Bristol-Myers Squibb Company; Miller, Michael Matthew; Mapelli, Claudio; Allen, Martin Patrick; Bowsher, Michael S.; Boy, Kenneth M.; Gillis, Eric P.; Langley, David R.; Mull, Eric; Poirier, Maude A.; Sanghvi, Nishith; Sun, Li-Qiang; Tenney, Daniel J.; Yeung, Kap-Sun; Zhu, Juliang; Reid, Patrick C.; Scola, Paul Michael; (892 pag.)US9308236; (2016); B2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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 1435-48-9 as follows. Product Details of 1435-48-9

Into a four necked RB flask of 1-lit capacity equipped with over head stirrer, a glass condenser and addition funnel, DCFB (250 g, 1.51 mol) and A1C13 (322 g, 2.41 mol) were added. The suspension was stirred at room temperature. Acetyl chloride (125 g, 1.60 mol) was added drop wise within two hours by maintaining the temperature 30-350C. After complete addition of acetyl chloride the mixture was quickly heated to 110-1200C for 5-6 hrs. The reaction kinetics was monitored by taking samples every two hrs. After the reaction was stopped the crude reaction mixture was cooled to ambient temperature. Then the reaction mixture was quenched using 1 kg ice and 500 ml water maintaining the temperature below 5O0C. The aqueous layer thus obtained was extracted with 200 ml of DCM thrice and combined all the extracts for evaporation. After the evaporation of DCM, 298.8g of brown product was obtained with the following composition.% Conversion of DCFB by GC = 76 % (24% DCFB as solvent)% DCFA = 68.64 %% Selectivity by GC = 91.5 %% Isomer = 4-5 %% DCFB = 24 %% H. B. = 4.1 %

According to the analysis of related databases, 1435-48-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ADITYA BIRLA SCIENCE & TECHNOLOGY CO. LTD.; MANDAL, Sisir; PATIL, Narendra; SULEMAN, Inamdur; MORE, Vinod; PURI, Prashant; WO2010/58421; (2010); A2;,
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. 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 3-Bromo-6-chloroimidazo[1,2-b]pyridazine

General procedure: To a solution under N2 of3-bromo-6-chloro-imidazo[1,2-b]pyridazine (1 g, 4.3 mmol) in dioxane (45 mL), Pd[P(C6H5)3]4(0.248 g, 0.2 mmol), 5-indole-5-boronic acid (0.728 g, 4.51 mmol) and Na2CO3(2 M, 7.7 mL) were added. The mixture was stirred for 21 h at 100 C. Thereaction was monitored by TLC. The solvent was evaporated under reducedpressure. The crude residue was diluted and stirred in AcOEt and ammoniumchloride solution (saturated). The product was extracted with AcOEt, and theorganic layer was washed with NaCl solution. The organic layer was dried overNa2SO4, filtered, and evaporated under reduced pressure.The crude residue was purified by chromatography on silica gel using DCM-AcOEt(6:4) afforded 6a in 72% yield(0.840 g) as a light green powder.

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 13526-66-4.

Reference:
Article; Bendjeddou, Lyamin Z.; Loaec, Nadege; Villiers, Benoit; Prina, Eric; Spaeth, Gerald F.; Galons, Herve; Meijer, Laurent; Oumata, Nassima; European Journal of Medicinal Chemistry; vol. 125; (2017); p. 696 – 709;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 108-70-3, 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 108-70-3 as follows.

1-Bromopropane (25 g, 0.20 mol) was added dropwise to a mixture of Mg (5.0 g, 0.21 mol) in diethyl ether (100 mL) at room temperature. The mixture was refluxed for 2 h and then cooled to room temperature. The new prepared Grignard reagent was then added to a mixture of 1,3,5-trichlorobenzene (10.4 g, 570 mmol) and Ni(dppe)Cl2 (75 mg, 0.14 mmol) in 100 mL of diethyl ether at room temperature. The mixture was stirred overnight and quenched by adding a saturated aqueous NH4Cl. The resulting mixture was extracted with ether, and washed with deionized water. The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography to give 1,3,5-trialkylbenzene (9.75 g, 84%) as a colorless oil.

According to the analysis of related databases, 108-70-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Liu, Taoping; Zhao, Xiaoming; Shen, Qilong; Lu, Long; Tetrahedron; vol. 68; 32; (2012); p. 6535 – 6547;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 39065-95-7, 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. 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a reaction flask were added 6-chloro-5-bromonicotinic acid (1.17 g, 4.97 mmol), 4-(chlorodifluoromethoxy)aniline (0.8 g, 4.15 mmol), dissolved with 20 mL anhydrous DMF, 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 2.1 g, 5.39 mmol) and N,N-diisopropylethylamine (DIPEA, 534 mg, 4.15 mmol) were added, and the reaction was stirred under nitrogen protection at room temperature for 18 hours. The reaction was diluted with large amount of water, extracted with ethyl acetate for 3-4 times, the organic layers were combined, washed with brine, concentrated, purified by column chromatography, dried in vacuum to afford 1.18 g of a product, yield: 69.5%.

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-(Chlorodifluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Shenzhen Targetrx, Inc.; WANG, Yihan; ZHAO, Jiuyang; AL, Yixin; (55 pag.)EP3553056; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics