Tag: M.W=200-300

Application of 1996-29-8,Some common heterocyclic compound, 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, molecular formula is C6H3BrClF, 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 a nitrogen atmosphere, 104.7 g of 2-fluoro-4-chlorobromobenzene, 400 ml of THF and 67.3 g of potassium t-butoxide were added to a 1 L three-necked flask.After cooling to -60 C, 300 mL of n-butyl lithium solution (2 mol / L) was added dropwise, and the addition was completed -50 to -60 CAfter heat preservation for 1 h, the temperature was raised to -30 C, and then 172.6 g of tributyl borate was added dropwise.After the completion of the dropwise addition, the temperature was naturally raised to room temperature for 2 hours.The reaction solution is acidified with hydrochloric acid, extracted with petroleum ether, and washed with water.Concentrated to a white solid a-1, 75.1 g, Y = 86.1%,LC = 98.15%. 2) Synthesis of a-2: under nitrogen protection,Add a-1 41.9g to a 250ml three-necked bottle.4-bromo resorcinol37.8g, potassium carbonate 27.6g,TBAB 2.0g, Pd(0) 0.5g, ethanol 100mL, water 50mL,After stirring at reflux for 3 h, the reaction solution was acidified with dilute hydrochloric acid.Extracted with ethyl acetate and concentrated.Recrystallization from 2 times ethanol gave a white solid a-2.38.5 g, Y = 80.7%, GC = 98.78%. 3) Synthesis of a-3: under nitrogen protection,Add a-223.9g to a 100ml three-necked bottle.DMF 70mL, 60% sodium hydride 8.0g,Reflow reaction for 0.5 h,The reaction solution was poured into ice water, neutralized with dilute hydrochloric acid, and extracted with ethyl acetate, and evaporated to give a yellow solid a-3, 20.9 g,GC=98.61% 4) Synthesis of a-4: A-320.9 g was sequentially added to a 100 ml three-necked flask.60 mL of dichloromethane,21.7 g of trimethylchlorosilane, reacted at room temperature for 0.5 h, concentrated,A yellow solid a-4, 27.8 g, Y = 100%, GC = 98.65%. 5) Synthesis of a-5: under nitrogen protection,Add a-423.3g to a 250 mL three-necked flask.THF 100ml, potassium t-butoxide 10.8g, after cooling to -50 C,60 mL of n-butyllithium solution (2 mol/L) was added dropwise.After the addition is completed, the temperature is kept at -50 to -40 C for 1 h.After heating to -30 C, 27.6 g of tributyl borate was added dropwise.After the completion of the dropwise addition, the temperature was naturally raised to room temperature for 2 hours. The reaction mixture was acidified with hydrochloric acid, extracted with EtOAc EtOAc.Y = 74.2%, LC = 98.66%. 6) Synthesis of a-6: Under nitrogen protection, 4-bromo resorcinol 9.5 g, a-5 17.8 g, potassium carbonate 13.8 g, TBAB 1.0 g were sequentially added to a 100 ml three-necked flask.Pd(0)0.2g, ethanol 50mL, water 20mL, reflux and stirring for 5h,The reaction solution was acidified with dilute hydrochloric acid, extracted with toluene, and concentrated.Recrystallization from 2 times ethanol gave a pale yellow solid a-6.13.1 g, Y = 71.9%, GC = 99.18%. 7) Synthesis of a-7: A-6 10.9 g was added to a 100 ml three-necked bottle in turn.50mL of dichloromethane, 9.4g of tetrabutylammonium fluoride,The reaction was refluxed for 1 h, washed with water and concentrated to give a pale yellow solid a-7.8.1 g, Y = 92.0%, LC = 98.76%. 8) Synthesis of a: under nitrogen protection,Add a-75.8g to a 100ml three-necked bottle.50 mL of dichloromethane and 9.1 g of triethylamine.The polymerization inhibitor is 0.01 g of hydroquinone, and a mixed solution of 7.5 g of methacryloyl chloride and 15 mL of dichloromethane is added dropwise in an ice water bath, and the mixture is naturally added to room temperature and stirred for 0.5 h after the dropwise addition.The reaction solution is acidified with dilute hydrochloric acid, washed with water and concentrated.Recrystallization from 1x ethanol and 2 times n-heptane mixed solvent,Purified by silica gel column to obtain product a, 5.2g, Y=52.5%,LC = 99.90%.

The synthetic route of 1996-29-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Xi’an Ruili Electronic Materials Co., Ltd.; Li Chao; Zhao Wen; Zhang Yanli; Jin Linuo; (35 pag.)CN109503534; (2019); A;,
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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. 1205-71-6, name is 4-Chloro-N-phenylaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Computed Properties of C12H10ClN

In a 250ml round bottom flask,10-bromobenzo [b] naphtho [2,1-d] furan (12 mmol), copper iodide (15 mmol), potassium tert-butoxide (65 mmol),1,2-diaminocyclohexane (12 mmol)And (4-chloro-phenyl) -phenylamine (12 mmol) were added to dry 1,4-dioxane (100 ml) and refluxed for 48 hours under N2 atmosphere. The obtained intermediate was cooled to room temperature, and added Water was then filtered through a pad of diatomaceous earth while being extracted with dichloromethane, then washed with water, and dried over anhydrous magnesium sulfate. After filtration and evaporation, the crude product was purified by silica gel column chromatography to obtain the intermediate HT002-1.

The synthetic route of 1205-71-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Tianma Organic Shine Display Co., Ltd.; Zhang Lei; Gao Wei; Niu Jinghua; Dai Wenpeng; Xiao Wenjing; Lu Yan; Zhu Hongyan; (28 pag.)CN110746391; (2020); A;,
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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 81927-55-1 as follows. Application In Synthesis of Benzyl 2,2,2-trichloroacetimidate

To a solution of scheme 58 compound Si (24 g, 0136 mol) and benzyl 2,2,2- thchioroaceiirnidate (5 1)3 g, 0204 inol) in cvchexanedichloromethane (600 inL120 ml..) at room temperature was added tritluorornethanesulfonic anhydride (cat. 1 .2 mE) dropwise. The reaction mixture was stirred at room temperature overnight and filtered. The filtrate was washed 4lth sat N& K (Y and hnne, dned o ci anh chous Na2SO- filteted and ctncentiated he residue was purified by column chromatography on silica gel (eluted with petroleum ether: ethyl aceiate =10: 1) to give the title compound (35 g, 933% yield) as a yellow oil.

According to the analysis of related databases, 81927-55-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason Allan; PHADKE, Avinash S.; DESHPANDE, Milind; AGARWAL, Atul; CHEN, Dawei; GADHACHANDA, Venkat Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; GREENLEE, William; (358 pag.)WO2017/35411; (2017); A1;,
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Application of 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.

General procedure: To a 50-ml glass round-bottom flask was added sequentially the primary amine 2 (1.0 mmol; aliphatic, aromatic or heteroaromatic; as free naked amine or as HCl, MsOH, TsOH or tartrate salt), FSO2N3 solution (containing 1.0 mmol FSO2N3, approximately 200 mM in DMF/MTBE 1:1, v/v, approximately 5 ml, volume adjusted according to the concentration; prepared according to the above procedure and diluted with equal volume of DMF) and aqueous KHCO3 solution (3.0 M, 1.33 ml, containing 4.0 mmol KHCO3). The reaction mixture was stirred for 5 min at room temperature, while monitoring by LC-MS. After completion, EtOAc (40 ml) was added and the mixture was washed sequentially with brine (60 ml × 6), water (60 ml × 2) and brine (60 ml), dried over Na2SO4, concentrated by rotary evaporation and dried under vacuum to afford the azide product 3. For products containing acidic functional groups, this extraction process was modified with acidified aqueous phase (acidified with aqueous HCl). Detailed procedures and the various modifications, as well as the characterization data for each compound, can be found in Supplementary Information 1.

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:
Article; Meng, Genyi; Guo, Taijie; Ma, Tiancheng; Zhang, Jiong; Shen, Yucheng; Sharpless, Karl Barry; Dong, Jiajia; Nature; vol. 574; 7776; (2019); p. 86 – 89;,
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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., name: 1-Bromo-3,5-dichlorobenzene

In the environment of nitrogen dissolved in I-20(85 g, 179 mmol) 700 mL of tetrahydrofuran (THF), where the 1-bromo-3,5-dichlorobenzene(48.5 g, 215 mmol) and tetrakis( triphenylphosphine) palladium was stirred into the (2.07 g, 1.79 mmol).Into a saturated potassium carbonate in water (61.8 g, 448 mmol) was heated to reflux at 80 ° C for 7 hours. After the reaction was completed, the reaction solution into water and extracted with dichloromethane (DCM) and then water was removed with anhydrous MgSO4, filter and was concentrated under reduced pressure. Thus separated and purified theresulting residue was purified by flash column chromatography compound to obtain a I-21(72.6 g, 82percent)

According to the analysis of related databases, 19752-55-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Cheil Industries Co., Ltd; Lee, Han Ir; Yu, Uhn Sun; Kang, Dong Min; Kang, Uii Soo; Yang, Yong Tak; Oh, Jae Jin; Yu, Dong Gyu; Lee, Sang Sin; Jang, Yuna; Jung, Su Young; Han, Su Jin; Hong, Jin Suk; (59 pag.)KR2015/6758; (2015); A;,
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50638-46-5, name is 4-Bromo-3-chloroanisole, 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. category: chlorides-buliding-blocks

Step 2: (E)-tert-Butyl 3-(4-((E)-2-(2-chloro-4-methoxyphenyl)-2-cyclobutyl-l-(4- morpholinophenyl)vinyl)phen l)acrylate[00401] A mixture of (E)-tert-butyl 3-(4-((Z)-2-cyclobutyl-2-(5,5-dimethyl-l ,3,2-dioxaborinan-2- yl)-l-(4-morpholinophenyl)vinyl)phenyl)acrylate (754 mg, 1.64 mmol), l -bromo-2-chloro-4- methoxybenzene (545 mg, 2.46 mmol), Pd(PPh3)2Cl2(1 15 mg, 0.16 mmol), and KOH (6M, 1.6 mL, 9.9 mmol) in 1 ,4-dioxane (10 mL) was heated to 90C for lh. After cooling, ethyl acetate and brine were added to the reaction mixture and the two layers were separated. The organic layer was washed with more brine, dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography on silica gel to afford 520 mg of the title compound as a yellow foam. 1H NMR (400 MHz, DMSO-d6): delta 7.37-7.33 (m, 3H), 7.1 1 (d, 1H), 7.04 (d, 2H), 6.95-6.90 (m, 5H), 6.82 (m, 1H), 6.34 (d, 1H), 3.74 (m, 4H), 3.71 (s, 3H), 3.42 (m, 1H), 3.13 (m, 4H), 1.87 (m, 3H), 1.67 (m, 2H), 1.46 (m, 1H), 1.43 (s, 9H); LCMS: 586 (M+H)+.

The synthetic route of 50638-46-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SERAGON PHARMACEUTICALS, INC.; SMITH, Nicholas, D.; GOVEK, Steven, P.; KAHRAMAN, Mehmet; BONNEFOUS, Celine; JULIEN, Jackaline, D.; WO2014/151899; (2014); 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. 468075-00-5, name is 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, A new synthetic method of this compound is introduced below., Application In Synthesis of 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene

General procedure: A mixture of (4-iodophenyl)(methyl)sulfane (Compound 4A) (500 mg, 2 mmol), 4-bromophenylboronic acid (400 mg, 2 mmol), Na2CCh (636 mg, 6 mmol), and Pd(PPh3)4 (115 mg, 0.1 mmol) in toluene/EtOH/H20 (20/10/4 mL) was stirred at 80 C under nitrogen overnight The mixture was concentrated under reduced pressure. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to afford Compound 4B. LC-MS (ESI) m/z: non-ionizable compound under routine conditions used. – NMR (CDCb, 500 MHz): d (ppm) 2.52 (s, 3H), 7.32 (d, J= 8.5 Hz, 2H), 7.43 (d, J= 8.5 Hz, 2H), 7.48 (d, J= 8.5 Hz, 2H), 7.55 (d, J= 8.5 Hz, 2H).

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; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHAO, Qi; (737 pag.)WO2019/133770; (2019); 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. 60811-21-4, name is 4-Bromo-2-chloro-1-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H3BrClF

EXAMPLE 76 5′-(3-Chloro-4fluorophenyl)-spiro[cyclopentane-1,3′-[3H]indol]-2′(1’H)-one A solution of 3-chloro-4-fluoro-bromobenzene (0.4 cm3, 0.66 g, 3.1 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.2 g) in ethylene glycol dimethyl ether (20 cm3) was stirred under N2 for 20 minutes. To this mixture was then added (spiro[cyclopentane-1,3′-[3H]indol]-2′(1’H)-one-5-yl) boronic acid (1.0 g, 4.7 mmol) and sodium carbonate (1.0 g, 9.4 mmol) in water (5 cm3). The solution was brought to reflux for 18 hours and then cooled to room temperature, poured into 2N NaOH and extracted with EtOAc (*3). The combined extracts were washed with water, brine, dried (MgSO4), and evaporated. The residue was purified by column chromatography (SiO2, EtOAc, hexane) to afford the title compound (0.65 g, 66%) as a pale-yellow solid. mp: 202-204 C.; 1H NMR (DMSO-d6) delta10.4 (s, 1H), 7.9 (dd, 1H, J=2.3, 4.9 Hz), 7.7-7.6 (m, 1H), 7.6 (d, 1H, J=1.5 Hz), 7.5 (s, 1H) 7.4 (d, 1H, J=1.8 Hz), 6.9 (d, 1H, J=8.0 Hz), 2.0-1.9 (m, 8H); MS [M-H]-=314.

According to the analysis of related databases, 60811-21-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; American Home Products Corporation; Ligand Pharmaceuticals, Inc.; US6391907; (2002); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 1435-50-3, A common heterocyclic compound, 1435-50-3, name is 2-Bromo-1,4-dichlorobenzene, molecular formula is C6H3BrCl2, 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.

Compound4-(4-(3-ethynyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester (0.20 g) , 0.51 mmol) was suspended in DMF (15 mL), and then Pd(PPh3)2Cl2 (36 mg, 0.051 mmol), CuI (10 mg, 0.051 mmol) and1,4-Dichloro-2-bromobenzene (0.12 g, 0.51 mmol). After the reaction liquid is exchanged for three times (nitrogen),Et3N (1.4 mL, 10.2 mmol) was added. After the reaction solution was stirred at 75 C for 2 hours under a nitrogen atmosphere,The organic layer was concentrated under reduced pressure. EtOAc (EtOAc)The organic phase obtained by liquid separation was dried over anhydrous Na2SO?The residue was subjected to silica gel column chromatography(PE/EtOAc(v/v)=1/2)Purification to give the title compound as a yellow solid(0.17 g, 62%).

The synthetic route of 1435-50-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Li Xiaobo; Zhou Shiqing; (62 pag.)CN103833753; (2017); B;,
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Adding a certain compound to certain chemical reactions, such as: 32943-25-2, name is 3-Chloro-10,11-dihydro-5H-dibenzo[b,f]azepine, 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 32943-25-2, Product Details of 32943-25-2

A solution of 3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepine (5.00 g, 21.8 mmol) (The Journal of Biological Chemistry (2009) 285, 11, 8363-8374) in toluene (50.0 mL) was treated with chloropropionyl chloride (2.18 mL, 22.9 mmol) and heated to 100 C for 1 h. The mixture was cooled to 25 C, concentrated under N2 stream, dissolved in a minimal amount of toluene and purified by flash chromatography (SiO2, 5-20% ethyl acetate-hexanes) to afford the title compound as an off-white solid (4.74 g, 68%). 1H NMR (600 MHz, CDCl3) (mixture of rotamers) 7.38 (1H, s), 7.29 (2H, br m), 7.25 (1H, m), 7.20 (1H, m), 7.14 (1H, m), 7.06 (1H, d, J = 8.2 Hz), [2H, 3.82 (br m), 3.77 (br m)], [2H, 3.39(br m), 3.33 (br m), 3.29 (t, J = 4.7 Hz)], 2.81 (3H, m), [1H, 2.57(t, J = 6.7 Hz), 2.53 (t, J = 6.8 Hz), 2.50 (t, J = 6.6 Hz)]; LCMS m/z 320.4 ([M + H+], C17H15Cl2NO requires 320.1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Chloro-10,11-dihydro-5H-dibenzo[b,f]azepine, and friends who are interested can also refer to it.

Reference:
Article; Kastrinsky, David B.; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S.; Narla, Goutham; Ohlmeyer, Michael; Bioorganic and Medicinal Chemistry; vol. 23; 19; (2015); p. 6528 – 6534;,
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