Tag: M.W=200-300

A common heterocyclic compound, 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene, 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. 1996-30-1.

[0136] A solution of 2-bromo-4-chloro-1-fluorobenzene (175 muL, 1.377 mmol) in THF (4.59 mL) at 78 C. was treated with n-BuLi (2.6 M, 741 muL, 1.928 mmol) and the reaction mixture was stirred for 30 min. To this was added tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (250 mg, 0.918 mmol) in one portion. The cooling bath was removed and the resulting reaction mixture was allowed to warm to rt and stirred for 1.5 h. Purification by automated flash silica gel chromatography using 10% EtOAc in hexanes afforded tert-butyl 4-(5-chloro-2-fluorobenzoyl)piperidine-1-carboxylate (287.9 mg, 92%) as a yellow oil. ESI-MS m/z [M+Na]+ 364.20

The synthetic route of 3-Bromo-4-fluorochlorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; Brown, Jason; Hitchcock, Steve; Hopkins, Maria; Kikuchi, Shota; Monenschein, Holger; Reichard, Holly; Schleicher, Kristin; Sun, Huikai; Macklin, Todd; US2015/175602; (2015); A1;,
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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. 60811-18-9 name is 4-Bromo-1-chloro-2-fluorobenzene, 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. 60811-18-9

[Example 112] Preparation of 4-(trans-4-(2-(trans-4-n-propyl-4-silacyclohexyl)ethyl)cyclohexyl)-3′-fluoro-4′-cyanobiphenyl 20.9 g (0.1 mol) of 1-bromo-4-chloro-3-fluorobenzene was dripped into a mixture of 2.5 g (0.11 mol) of magnesium and 300 ml of THF to obtain a Grignard’s reagent. This solution was then dripped into a 500 ml THF solution of 0.5 g of tetrakis triphenylphosphine palladium and 43.6 g (0.1 mol) of 4-(trans-4-(2-(trans-4-n-propyl-4-silacyclohexyl)ethyl)cyclohexyl)phenyl bromide. After a conventional after treatment, purification was conducted by means of chromatography to obtain 36.4 g (yield 75.1%) of 4-(trans-4-(2-(trans-4-n-propyl-4-silacyclohexyl)ethyl)cyclohexyl)-3′-fluoro-4′-cyanobiphenyl was obtained.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-1-chloro-2-fluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Shin-Etsu Chemical Co., Ltd.; US5582764; (1996); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 33863-76-2, name is 1-Bromo-3-chloro-5-fluorobenzene, 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 13-Chloro-5-{[5-chloro-l-(lH-pyrazolo[3,4-]pyridin-3-ylmethyl)-lH-indazol-4- yl] oxy } benzonitrileStep 1 : 3-Bromo-5-chlorophenyl 2-chloro-5-fluorophenyl ether; To a solution of 2-chloro-5-fluorophenol ( 82.3 g, 562 mmol) and l-bromo-3- chloro-5-fluorobenzene (124g, 590 mmol) in NMP (200 mL) was added potassium carbonate (155g, 1.123mol). The resulting mixture was then heated to 1400C and maintained at 14O0C for 30 hours, after which the mixture was poured into water (1500 mL) and extracted with EtOAc (2500 + 1500 mL). The combined extracts were washed with water and brine. This solution was concentrated on the rotary evaporator and the residue was distilled at high vacuum at 135-1900C to give the title compound as a clear, colorless liquid. leta NMR (CDCI3) delta 7.45 (dd, 1eta, J=9.0 and 4.5 hz), 7.28(dd, 1eta, J=I .7Hz), 7.26(s, IH), 7.00(dd, Ih, J=I .95Hz), 6.92(ddd, IH, J=10.5, 7.6 and 2.7Hz), 6.89(dd, IH, J=I.95Hz).

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 33863-76-2.

Reference:
Patent; MERCK & CO., INC.; WO2008/76223; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1127-85-1, name is 2,4-Dichloro-5,6,7,8-tetrahydroquinazoline, 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. 1127-85-1

Reference Example 38(R)-N-{ 1 -(2-chloro-5,6,7,8-tetrahydroquinazolin-4-yl)piperidin-3-yl}acetamide10205] (R)-(-)-3-aminopiperidine dihydrochloride (940mg, 5.42 mmol) was added to chloroform (25 ml) solution of2,4-dichloro-5,6,7,8-tetrahydroquinazoline (1 g, 4.92 mmol) prepared in Reference Example 33 and diisopropylethylamine (3.5 ml, 20.2 mmol), and then they were stirred at 60 C. overnight. Acetyl chloride (0.39 ml, 5.42 mmol) was added thereto at room temperature, and they were stirred for 2 days. The reaction solution was diluted with dichloromethane, washed with water, dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate=5/1) to give the titled compound (1.2 g) as a white solid.j0206] ?H NMR (400 MHz, CD3OD) oe 7.41 (m, 1H), 7.23 (m, 1H), 7.14 (m, 1H), 4.19-3.98 (m, 5H), 3.15 (m, 2H), 2.49 (m, 1H), 2.46 (m, 3H), 2.30 (s, 3H), 2.25 (m, 1H+3H), 1.36 (m, 3H).

Statistics shows that 1127-85-1 is playing an increasingly important role. we look forward to future research findings about 2,4-Dichloro-5,6,7,8-tetrahydroquinazoline.

Reference:
Patent; YUHAN CORPORATION; SIM, Jae Young; CHA, Myung; KIM, Tae Kyun; YOON, Young Ae; KIM, Dong Hoon; (59 pag.)US2016/90374; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2770-11-8, 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. 2770-11-8, name is 2-(4-Chlorophenoxy)aniline, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 2-(4-chloro-phenoxy)-phenylamine (100 mg, 0.46 mmol) and N-(2-formyl- phenyl)-acetamide (74 mg, 0.46 mmol) in anhydrous DCM (5ml) was stirred at r.t. and to this was added TiCl(O1Pr)3 (0.25 mL, 1 mmol). The resulting mixture was stirred for a further 4 h at room temperature. The mixture was then evaporated to dryness to yield the desired product. As in Method 1 (see above) the product could easily be identified by 1H NMR. The product was used crude in all following experiments.1H NMR (CDCl3, 270 MHz,): delta 2.03 (3H, s, CH3), 6.87-7.46 (HH, m, ArH), 8.60 (IH, s, N=CH), 8.72 (IH, d, J= 8.5 Hz, ArH). 13C NMR (CDCl3, 101 MHz): 24.9 (CH3), 116.7, 119.2, 119.6, 120.3 (ArCH), 120.6 (ArC), 122.5, 125.0, 127.9 (ArCH), 128.2 (ArC), 129.8, 132.7 (ArCH), 140.4, 141.7, 149.6, 156.1 (ArC), 163.4 (CH), 169.9 (CO).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; STERIX LIMITED; WO2009/66072; (2009); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, 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. 1996-29-8

Under an argon gas atmosphere, in the presenceof catalytic amount iodine, to THF (50 mL) suspension of magnesium (1.28 g, 52.5 mmol), THF solutionof 1-bromo-4-chloro-2-fluorobenzene (10.0 g, 47.8mmol) was dropped at 40 (oil bath temperature), to prepare a Grignard reagent. This Grignard reagentwas dropped under -50 to THF solution of diethyl oxalate (8.37g, 57.3mmol), and the mixturewas gradually heated to room temperature andstirred for 18 hours. After completion of the reaction, the reactionsolution was poured into ice and acidified with concentrated hydrochloric acidand extracted with ether (100mL ¡Á 2,50mL ¡Á 1). The organic layer was dried overanhydrous magnesium sulfate and then concentrated under reduced pressure togive orange oily crude product (12.9g). This was purified by silica gel columnchromatography (hexane: ethyl acetate = 10: 1) to give yellow oil of 2-(4-chloro-2-fluorophenyl) -2-oxoethyl acetate (4.17 g, yield: 41%).

Statistics shows that 1996-29-8 is playing an increasingly important role. we look forward to future research findings about 1-Bromo-4-chloro-2-fluorobenzene.

Reference:
Patent; SAGAMI CHEMICAL RESEARCH INSTITUTE; KAKEN PHARMACEUTICAL COMPANY LIMITED; KOBAYASHI, OSAMU; TAKATSUNA, REIKO; NIIKURA, NAOKO; MATSUKAWA, TOMOKO; NAKAMURA, SHINJI; HIRAI, KENJI; KOCHI, SHINICHIRO; KAWANISHI, NAOKI; YAMADA, OSAMU; (75 pag.)JP2016/56157; (2016); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

13526-66-4, 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. 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, A new synthetic method of this compound is introduced below.

13.9 g (59.8 mmol) 3-bromo-6-chloro-imidazo[1 ,2-b]pyridazine were suspended in 508 mL 1 ,4-dioxane. 10.1 g (62.8 mmol) 2-benzofuranylboronic acid, 2.76 g (2.29 mmol) tetrakis(tn’phenylphosphino)palladium-(0) and 19.0 g (179 mmol) sodium carbonate were added. The obtained mixture was heated to 100C for 24 h.400 mL of a saturated aqueous ammonium chloride solution were added. The obtained mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. After evaporation of the solvent, the obtained solid material was digested in 40 mL of a mixture of dichloromethane and methanol (8:2), filtered off and dried in vacuo to yield 5.42 g (44%) of the title compound as solid material.1H-NMR (300 MHz, DMSO-d6): delta [ppm]= 7.23 – 7.40 (m, 2H), 7.51 (d, 1 H), 7.59 – 7.67 (m, 2H), 7.77 (d, 1 H), 8.33 – 8.40 (m, 2H).LCMS (Method 1 ): Rt = 1.35 min; MS (ESIpos) m/z = 270 [M+H]+.

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; Bayer Intellectual Property GmbH; EIS, Knut; PUeHLER, Florian; ZORN, Ludwig; SCHOLZ, Arne; LIENAU, Philip; GNOTH, Mark, Jean; BOeMER, Ulf; GUeNTHER, Judith; FANGHAeNEL, Joerg; KORR, Daniel; WO2012/175591; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

933190-51-3, Adding some certain compound to certain chemical reactions, such as: 933190-51-3, name is 8-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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 933190-51-3.

Comparative Example 1 e 8-Bromo-6-chloro-3-iodoimidazo 1 ,2-b]pyridazine A mixture comprising 100 g (430 mmol) 8-bromo-6-chloroimidazo[1 ,2- b]pyridazine which was prepared according to a procedure described in US2007/78136 (WO2007/38314), 145 g N-iodosuccinimide, 5 percent per weight cone, hydrochloric acid and 1 L trichloromethane was heated at reflux for 6 hours. 20 g N-iodosuccinimide were added and heating was continued for additional 3 hours. The precipitate was removed and the filtrate was washed with 1 N sodium hydroxide solution, brine and dried over sodium sulfate. After filtration and removal of solvent diisopropyl ether was added and the residue was stirred at 23 C overnight. The precipitate was filtered off and dried to give 66.6 g (43%) of the title compound.

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 933190-51-3.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; WENGNER, Antje, Margret; SIEMEISTER, Gerhard; WO2014/198776; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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

General procedure: To a solution of 6a-6c (1 mmol) in THF (5 mL) was addedmorpholine (or (S)-3-methylmorpholine, or 8-oxa-3-azabicyclo[3.2.1]octane) (1.2 mmol) and Et3N (2.2 mmol). The mixture washeated under reflux for 12 h. The crude product was extracted with CH2Cl2, dried over Na2SO4, purified over silica gel chromatographyeluting with PE and EtOAc to give 7a-7g [43].

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, 8-Bromo-6-chloroimidazo[1,2-b]pyridazine, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Mao, Beibei; Gao, Shanyun; Weng, Yiran; Zhang, Liangren; Zhang, Lihe; European Journal of Medicinal Chemistry; vol. 129; (2017); p. 135 – 150;,
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 24279-39-8 as follows. 24279-39-8

Reference Production Example 10 First, 31.4 g (120 mmol) of triphenylphosphine and 4.9 g (48 mmol) of triethylamine were added to 20 ml of carbon tetrachloride, to which 3.8 g (40 mmol) of difluoroacetic acid was added dropwise under ice cooling. After completion of the dropwise addition, the mixture was stirred under ice cooling for 10 minutes. Then, a solution of 9.2 g (40 mmol) of 2,6-dichloro-4-trifluoromethylaniline in 20 ml of carbon tetrachloride was added dropwise to the reaction mixture, which was heated at 80 C. for 6 hours. The reaction mixture was concentrated under reduced pressure, followed by addition of hexane, and undissolved matter was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 6.0 g of N-(2,6-dichloro-4-trifluoromethylphenyl)-2,2-difluoroacetimidoyl chloride. 1H-NMR (300 MHz, CDCl3/TMS): delta (ppm)=7.65 (s,21), 6.38 (t, J=54.1 Hz, 1H)

According to the analysis of related databases, 24279-39-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Matsumoto, Osamu; Uekawa, Toru; US2001/41740; (2001); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics