Month: June 2021

Electric Literature of 363-51-9,Some common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, molecular formula is C6H5ClFN, 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 mixture of 2-chloro-6-fluoroaniline (2.23 g, 15.32 mmol) in propionic acid (7.66 ml) was treated with propionic anhydride (2.369 ml, 18.38 mmol), and the reaction mixture was stirred at 90 C. for 1 h. After cooling to r.t., water was added and the solid precipitate was collected by filtration, washed with water, and air dried. The crude product obtained was used directly in the next step without further purification. LCMS calculated for C9H10ClFNO (M+H)+: m/z=202.0; Found 202.1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-6-fluoroaniline, its application will become more common.

Reference:
Patent; Incyte Corporation; Hummel, Joshua; Vechorkin, Oleg; Sokolsky, Alexander; Ye, Qinda; Liu, Kai; Yao, Wenqing; (60 pag.)US2020/48241; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 918538-05-3,Some common heterocyclic compound, 918538-05-3, name is 2,4-Dichloropyrrolo[2,1-f][1,2,4]triazine, molecular formula is C6H3Cl2N3, 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 mixture of 2,4-dichloropyrrolo[1,2-f][1,2,4]triazine (150 mg, 0.8 mmol), 2-oxa-6-azaspiro[3.3]heptane (103mg, 1.04 mmol) and K2C03 (221 mg, 1.6 mmol) in DMF (4.5 mL) was stirred at room temperature for 2h. TLC showed the starting material was completely consumed and DCM (10 mL) was added to the mixture, and the mixture was washed with water (5 mL) and brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to give compound 35(160 mg, 8 1%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,4-Dichloropyrrolo[2,1-f][1,2,4]triazine, its application will become more common.

Reference:
Patent; SUZHOU KINTOR PHARMACEUTICALS, INC.; GUO, Chuangxin; TONG, Youzhi; (160 pag.)WO2017/219800; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, molecular formula is C6H3BrClN3, 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. Safety of 3-Bromo-6-chloroimidazo[1,2-b]pyridazine

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 90 mL (180 mmol) of a 2M aqueous sodium carbonate solution 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 (2H), 7.51 (1 H), 7.59 – 7.67 (2H), 7.77 (1 H), 8.33 – 8.40 (2H). LCMS (Method 1 ): Rt = 1.35 min; MS (ESIpos) m/z = 270 [M+H]

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 13526-66-4, its application will become more common.

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; EIS, Knut; PUeHLER, Florian; ZORN, Ludwig; SCHULZE, Volker; SUeLZLE, Detlev; LIENAU, Philip; HAeGEBARTH, Andrea; PETERSEN, Kirstin; BOeMER, Ulf; WO2013/144189; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

6579-54-0, name is 2,6-Dichlorobenzenesulfonyl 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. Formula: C6H3Cl3O2S

C. 3-(2,6-dichlorophenylsulfonylamino)-4-(2-pyridyl)-5-(3-(4-fluorophenoxy)benzylthio)-(1H)-pyrazole 3-Amino-4-(2-pyridyl)-5-(3-(4-fluorophenoxy)benzylthio)-(1H)-pyrazole (0.39 g, 0.99 mmol) was dissolved in 5 ml of pyridine. Commercial 2,6-dichlorobenzenesulfonyl chloride (0.26 g, 1.04 mmol) was added and the red solution was stirred overnight at room temperature. The reaction mixture was poured into 50 ml of water and was extracted twice with 100 ml portions of ethyl acetate. The organic layers were washed with water and brine, combined, dried over MgSO4and concentrated. The crude product was slurried in cold ethyl acetate and the solid was filtered off and washed with small portions of cold ethyl acetate and cold diethyl ether and dried under vacuum to afford 0.32 g (53% yield) of the final compound. FD-MS: (M+)600 mp. 164-5C

The synthetic route of 6579-54-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; EP846687; (1998); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 1435-44-5,Some common heterocyclic compound, 1435-44-5, name is 1-Chloro-2,4-difluorobenzene, molecular formula is C6H3ClF2, 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.

EXAMPLE 81 3-(2,4-Difluorophenylamino)-8-nitro-6H-dibenzo[b,e]oxepin-11-one (7) In accordance with general method Z, 0.50 g (1.85 mmol) of (6), 0.28 g (1.89 mmol) of 1-chloro-2,4-difluorobenzene, 2 spatula tips of Pd(OAc)2, 0.09 g of 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (phosphine ligand), 0.50 g of KOt-Bu, 1.5 ml of t-BuOH are weighed out and dissolved in 10 ml of toluene (anhydrous). The mixture is refluxed at 100 C. under an argon atmosphere for 4 h. The crude product is purified by chromatography over silica gel with MC/EtOH (98/2). Yield: 0.05 g (7.0%); melting point: 210-214 C. C20H12F2N2O4 (Mr=382.33); LC 8.97 min 1H-NMR (DMSO-d6) delta in ppm: 8.84 (s, 1H, aryl H), 8.48 (d, 1H, J=2.01 Hz, aryl H), 8.30 (m, 1H, aryl H), 8.01 (dd, 2H, J1=2.70 Hz, J2=3.25 Hz, aryl H), 7.47-7.33 (m, 2H, aryl H), 7.15-7.04 (m, 2H, aryl H), 6.63 (d, 1H, J=10.0 Hz, aryl H), 6.24 (s, 1H, aryl H), 5.34 (s, 2H, -CH2-O) 13C-NMR (DMSO-d6) in ppm: 186.11 (C11), 163.30 (C4a), not detected (C4′, C2′), 152.89 (C8), 149.52 (C3), 145.34 (C6a), 137.76 (C10a), 133.85 (C1), 131.01 (C10), 127.38 (C1′, J=9.85 Hz), 124.23 (C6′, J=14.23 Hz), 116.52 (C7), 112.57 (C5′, J=3.52 Hz), 110.35 (C2), 105.45 (C3′, J=24.29 Hz), 101.93 (C4), 72.03 (C6) IR (ATR) (cm-1): 2849, 1643, 1608, 1531, 1297, 1249, 1150, 740 MS (ESI) 381.1 [M-H]-. General Method ZThe stated amounts of 3-amino-8-nitro-6H-dibenzo[b,e]oxepin-11-one, phosphine ligand, KOt-Bu, tert-butanol, haloaromatic, Pd(OAc)2 are weighed into a dry 100 ml three-necked flask with a reflux condenser, bubble counter and thermometer. The mixture is suspended in toluene (anhydrous) under an argon atmosphere and the suspension is heated to 110 C. and refluxed for 2 h. Hydrolysis with ice-water and repeated extraction with EtOAc are carried out. The combined organic phases are filtered and then concentrated in vacuo. The residue is purified by chromatography.

The synthetic route of 1435-44-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Laufer, Stefan; Albrecht, Wolfgang; US2012/115862; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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, HPLC of Formula: C15H14BrClO

Step 6: (3R, 4S, 5R, 6R) -3, 4, 5-tris (benzyloxy) -6- ( ( (tert-butyldimethylsilyl) oxy) methyl) -2- (4-chloro-3- (4-ethoxybenzyl) phenyl) tetrahydro-2H-pyran-2-ol (5f) To a solution of 4-bromo-1-chloro-2- (4-ethoxybenzyl) benzene (619 mg, 1.91 mmol) in anhydrous PhMe /THF (2:1, 12 mL) was added n-BuLi (2.4M in hexane, 0.8 mL, 1.91 mmol) dropwised at -78under nitrogen. The mixture was stirred at -78for 1 h. A mixture of compound 5e (978 mg, 1.74 mmol) in anhydrous PhMe /THF (2:1, 12 mL) was added dropwise and stirred -78for another 1 h. Then the mixture was increased from -78to -25 , and to the mixture was dropwisely added saturated NH4Cl solution (20mL) and extracted with DCM (3×15 mL) . The organic extracts were dried over MgSO4, and concentrated to produce a residue, which was purified by chromatography (200300 mesh silica gel, eluted with EtOAc/PE 1:3-1:1) to give compound 5f as a pale oil (mainly beta-epimer, 760 mg, 54) LC-MS (ESI) : 826.34 [M+NH4]+.

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; NATIONAL INSTITUTE OF BIOLOGICAL SCIENCES, BEIJING; ZHANG, Zhiyuan; HUANG, Shaoqiang; ZHANG, Zhaolan; SU, Yaning; REN, Yan; (73 pag.)WO2016/41470; (2016); 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. 627531-47-9, name is 4-Bromo-3-chloro-2-methylaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Product Details of 627531-47-9

Concentrated HCl was added to a solution of 4-bromo-3-chloro-2-methyl-phenylamine (4.98 g, 22.60 mmol) in EtOH. NaNO2 (3.00 g, 43.50 mmol) was added and the resulting mixture was heated to 70 C. for 2 hours. Ethanol was distilled off and the residue was purified by column chromatography using hexanes as the eluant to afford the title compound. Spectroscopic data: 1H NMR (300 MHz, CDCl3) delta 2.43 (s, 3H), 7.01 (t, J=7.91 Hz, 1H), 7.18 (d, J=7.62 Hz, 1H), 7.47 (d, J=7.91 Hz, 1H).

The synthetic route of 627531-47-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Allerghan, Inc.; US2008/194650; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 348-59-4, These common heterocyclic compound, 348-59-4, name is 2,5-Dichlorofluorobenzene, 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.

Intermediate 124 2,5-Dichloro-4-fluorobenzenesulfonyl chlorideA mixture of 1 ,4-dichloro-2-fluorobenzene (5 g, 30.3 mmol) and fuming sulfuric acid (18- 24% SO3, 20 ml) was heated at 1 10 0C overnight. After cooling down to room temperature, the reaction mixture was carefully poured into ice (700 g). The resulting mixture was stirred at room temperature for 30 min followed by addition of ethyl acetate. The aqueous layer was isolated and concentrated under vacuum. The precipitate was filtered off to give 2,5-dichloro-4-fluorobenzenesulfonic acid as white crystals (3.33 g, 45%).The acid previously prepared (2.0 g, 8.2 mmol) and phosphorus pentachloride (5 g, 24 mmol) were heated at 110 0C overnight. After cooling down to room temperature, the reaction mixture was carefully poured into ice (50 g) The resulting mixture was stirred at room temperature for 30 min followed by addition of ethyl acetate (100 ml_). The ethyl acetate layer was isolated and concentrated under vacuum to give the title compound as yellow oil (1.29 g, 60%). 1H NMR(d6-DMSO) delta 7.62 (d, 1 H), 7.95 (d, 1 H).

Statistics shows that 2,5-Dichlorofluorobenzene is playing an increasingly important role. we look forward to future research findings about 348-59-4.

Reference:
Patent; GLAXO GROUP LIMITED; WO2009/26197; (2009); A1;,
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 202197-26-0 as follows. Safety of 3-Chloro-4-((3-fluorobenzyl)oxy)aniline

To 2-propanol (300 mL) were sequentially added 4-chloro-5,8-dihydro-6H-spiro[l- benzothieno[2,3-d]pyrimidme-7,2′-[l,3]dioxolane] (20.7 g, 73.2 mmol), 3-Chloro-4-(3- fluoro-benzyloxy)-phenylamine (18.4 g, 73.2 mmol), and HCl in dioxane (4N, 0.92 mL). The suspension was stirred with heating to 80 0C, upon which the contents turn brown and homogeneous. After 15 h, the dark orange-yellow heterogeneous mixture was removed from heating, and allowed to cool to rt. The contents were filtered and the collected solid product dried under vacuum. The filtrate was concentrated under reduced pressure and the EPO residue suspended in CH3OH (50 niL), upon which formation of a second crop of product ensues. The second crop was collected, and from this filtrate a third crop could also be obtained. The solid product crops were combined to afford the final product (33.5 g, 92%) as an off-white solid. 1H-NMR delta 1.90 (t, 2H), 3.00 (s, 2H), 3.26 (t, 2H), 3.97 (s, 4H), 5.22 (s, 2H), 7.11-7.30 (m, 4H), 7.41-7.55 (m, 2H), 7.74 (s, IH), 8.33 (s, IH), 8.39 (s, IH); LCMS RT = 3.63 min; [M+H]+ = 498.3.

According to the analysis of related databases, 202197-26-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER PHARMACEUTICALS CORPORATION; WO2006/55268; (2006); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 2453-46-5, name is Chlorocycloheptane, 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 2453-46-5, name: Chlorocycloheptane

General procedure: A 10 mL Schlenk tube was charged with CoBr2 (6.6 mg, 0.03mmol), 1,3-diisopropyl-1H-benzimidazol-3-ium bromide (L4; 8.5mg, 0.03 mmol), 4-methoxy-N-[(1E)-1-phenylethylidene]aniline(1a, 67.6 mg, 0.30 mmol), 1-chlorooctane (2a, 76.5 muL, 0.45 mmol), and THF (0.69 mL). A 1.92 M solution of t-BuCH2MgBr inTHF (0.31 mL, 0.60 mmol) was added dropwise at 0 C, and themixture was stirred at r.t. for 6 h. The reaction was quenched by theaddition of 3 M aq HCl (1.0 mL), and the mixture was stirred at r.t.for 1 h, then extracted with EtOAc (3 × 10 mL). The organic layerswere combined, dried (MgSO4), and concentrated under reduced pressure. The crude product was purified by chromatography [silicagel, hexane-EtOAc (40:1)].

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:
Article; Gao, Ke; Yamakawa, Takeshi; Yoshikai, Naohiko; Synthesis; vol. 46; 15; (2014); p. 2024 – 2039;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics