Month: March 2021

Reference of 54535-22-7,Some common heterocyclic compound, 54535-22-7, name is Diethyl 2-((phenylamino)methylene)malonate, molecular formula is C14H17NO4, 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 I L three-necked flask fitted with a mechanical stirrer was charged with 2- phenylaminomethylene-malonic acid diethyl ester (26.3 g, 0.100 mol), polyphosphoric acid (270 g) and phosphoryl chloride (750 g). The mixture was heated to 70 C and stirred for 4 h. The mixture was cooled to room temperature and filtered. The residue was treated with aqueous Na2C03 solution, filtered, washed with water and dried. 4- Hydroxyquinoline-3-carboxylic acid ethyl ester was obtained as a pale brown solid (15.2 g, 70%). The crude product was used in next step without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Diethyl 2-((phenylamino)methylene)malonate, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; HASELTINE, Eric L.; MOSKOWITZ, Samuel; ROBERTSON, Sarah; WALTZ, David; (167 pag.)WO2018/227049; (2018); A1;,
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Adding a certain compound to certain chemical reactions, such as: 46004-37-9, name is Methyl 4-amino-2-chlorobenzoate, belongs to esters-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 46004-37-9, Product Details of 46004-37-9

Methyl-2-chloro-4-(methylsulfonamido) benzoate (101).; To a stirred solution of methyl-2-chloro-4-amino benzoate 100 (0.457 g, 2.45 mmol) in DCM cooled to 0 0C was added pyridine (2 mL) followed by dropwise addition of methanesulphonyl choride (0.2 mL, 2.5 mmol). After addition was complete, the reaction was allowed to warm to room temperature and stirred for 2 h. After completion, the reaction mixture was concentrated in vacuo. 1 N HCl (5 mL) was added to the residue and the mixture extracted with EtOAc (10 mL). The organic phase was dried over Na2SO4 and concentrated under high vacuum. The crude compound was purified by column chromatography to afford the title intermediate 101 as a solid (0.54 g, 84% yield).

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, Methyl 4-amino-2-chlorobenzoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EXELIXIS, INC.; CANNE BANNEN, Lynne; CHAN, Diva Sze-ming; GU, Xiao-hui; MAC, Morrison, B.; NG, Stephanie; WANG, Tie-lin; WANG, Yong; XU, Wei; WO2010/65760; (2010); A1;,
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924-99-2, name is Ethyl 3-(dimethylamino)acrylate, belongs to esters-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. Safety of Ethyl 3-(dimethylamino)acrylate

220g of toluene, 95g of triethylamine, 200g acid chloride sequentially into the acylation reactor, open stirring, cooling to 13 ;Preparation of the first 98g N, N-dimethylamino ethyl acrylate added to the dropping device, keeping the reaction kettle temperature 12 open stirring dropping,25 minutes to complete all the dropwise addition is completed, slowly heated to 75 C and incubated for 6 hours; step is completed, cooled to20 C, into 60g L-aminopropanol, slowly heated to 45 C, incubated for 3 hours, was added 200g saturated brine,Slowly add dropwise adjust PH5.5, stirring for 20 minutes, retest PH value after stopping stirring Stirred stratification, toluene layer decompression recovery of tolueneNo toluene solution into the reactor, pumped DMF200g stirring dissolved into the ring reactor high tank to be used; to the reaction within the reactorInto DMF1500g, start stirring, cast KF130g, temperature and pressure before recovery fraction to the reactor temperature 160 . Add amineThe reaction solution was heated to maintain refluxing heat 4 hours; end of the insulation, cooling to below 100 , DMF was recovered under reduced pressureWill be dry. After the end of the recovery of high pure water 1200g, stirred for 40 minutes, filtered, washed with water, finally rinsed with methanol, dried, too176g product, 96.8% molar yield.

The synthetic route of 924-99-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Yancheng Xin’an Zhou Pharmaceutical Co., Ltd.; Chen Chengle; Zhang Wenbiao; (6 pag.)CN106565745; (2017); A;,
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Related Products of 952285-52-8, A common heterocyclic compound, 952285-52-8, name is Methyl 4-amino-2,5-difluorobenzoate, molecular formula is C8H7F2NO2, 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) Synthesis of methyl 2,5-difluoro-4-[(4-nitrophenyl)sulfonylamino]benzoate A 4-nitro benzene sulfonyl chloride (8.9 g, 40.1 mmol) was added to a pyridine solution (30 ml) of methyl 4-amino-2,5-difluoro-benzoate (3.0 g, 16.0 mmol), followed by stirring at 50?C for 18 hours. The resultant mixture was concentrated under reduced pressure, and the residue was slurry washed using acetonitrile to obtain methyl 4-[bis[(4-nitrophenyl)sulfonyl]amino]-2,5-difluoro-benzoate (11.6 g).

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; EA Pharma Co., Ltd.; TOKUMASU Munetaka; NOGUCHI Masatsugu; KAWAHIRA Mizuki; IWASAKI Kana; HAYAKAWA Nobuhiko; MIYANAGA Wataru; SAITOU Yuki; YAMAURA Yui; ANDO Ayatoshi; TSURUTA Atsushi; NOGUCHI Misato; (127 pag.)EP3412660; (2018); A1;,
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Application of 40876-98-0, These common heterocyclic compound, 40876-98-0, name is Sodium 1,4-diethoxy-1,4-dioxobut-2-en-2-olate, 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: A mixture of malononitrile (3) (0.01 mol), isatin (4) (0.01 mol) and Et3N (1mL) in EtOH (10 mL) was stirred at room temperature for 0.5 h. Next, a mixture of diethyl oxalacetate sodium salt (1) (0.01 mol) and hydrazine hydrate (4) (0.01 mol) in AcOH (10 mL) was added. After reaction completion, the resulting precipitate was collected by filtration and the crude product was recrystallized from EtOH.

The synthetic route of 40876-98-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Gein, Vladimir L.; Zamaraeva, Tatiana M.; Slepukhin, Pavel A.; Tetrahedron Letters; vol. 58; 2; (2017); p. 134 – 136;,
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Synthetic Route of 33689-29-1,Some common heterocyclic compound, 33689-29-1, name is Methyl 1-hydroxycyclopropanecarboxylate, molecular formula is C5H8O3, 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.

Compound 1-8A mixture of Inter mediate-2 (15 mg, 1 equiv.) and methyl 1-hydroxycyclopropanecarboxylate (14 mg, 3 equiv.) in THF was cooled to -78 C. Contents were treate with sodium hydride (5.3 mg, 60% suspension in mineral oil, 3 equiv.) and warmed to 23 C and stirred for 18 h. The contents were concentrated in vacuo, and the residue was purified via silica gel chromatography utilizing a 0-30% ethyl acetate/hexanes gradient to deliver the desired compound (16 mg, 84%>) as a white solid. 1H-NMR (500 MHz, CDCb) delta 8.47 (s, 2 H), 7.23-7.17 (m, 1 H), 7.16 (s, 1 H), 7.02 (t, 1 H), 6.98 (t, 1 H), 6.93-6.88 (m, 1 H), 6.58 (s, 1 H), 5.95 (s, 2 H), 3.70 (s, 3 H), 1.76-1.71 (m, 2 H), 1.45-1.40 (m, 2 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 1-hydroxycyclopropanecarboxylate, its application will become more common.

Reference:
Patent; IRONWOOD PHARMACEUTICALS, INC.; RENNIE, Glen Robert; PERL, Nicholas; LEE, Thomas Wai-Ho; RENHOWE, Paul Allan; NAKAI, Takashi; MERMERIAN, Ara; IM, G-Yoon Jamie; (235 pag.)WO2016/44445; (2016); A2;,
Ester – Wikipedia,
Ester – 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. 46064-79-3, name is Methyl 3-amino-4-bromobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Computed Properties of C8H8BrNO2

A mixture of methyl 2-hydroxy-5,5-dimethylcyclohex-1-enecarboxylate (26 g, 0.141 mol), methyl 3-amino-4-bromobenzoate (25 g, 0.109 mol), polyphosphoric acid (220 g) and dioxane (220 mL) was heated at 130 C for 5 hours. After cooling, the mixture was diluted with water. The resulting precipitate was collected by filtration and dried. The solid was suspended in methanol (400 mL), and TMSCl (90 mL) was added. The mixture was stirred at reflux for 5 hours, concentrated and treated with water (80 mL), extracted with ethyl acetate (250 mL). The organic layer was separated, concentrated and recrystallized with methanol to afford desired compound (10.6 g, 27%).

The synthetic route of 46064-79-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BEIGENE, LTD.; ZHOU, Changyou; REN, Bo; WANG, Hexiang; WO2013/97226; (2013); A1;,
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Electric Literature of 1000342-11-9, A common heterocyclic compound, 1000342-11-9, name is Methyl 3-amino-5-bromo-2-methylbenzoate, molecular formula is C9H10BrNO2, 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.

Methyl 5-bromo-2-methyl-3-((tetrahydro-2H-pyran-4-yl) amino) benzoate (2) A reactor was charged with methyl 3-amino-5-bromo-2-methylbenzoate (455.8 g, 1.87 mol), 1,2- Dichloroethane (4.56 L), and acetic acid (535 ml, 9.34 mol). To the mixture were added dihydro-2H-pyran-4(3H)-one (280 g, 2.80 mol) and sodium triacetoxyborohydride (594 g, 2.80 mol) maintaining the internal temperature below 40 C. The mixture was stirred at 25 C for 2.5 h and then the reaction was quenched with a solution of sodium hydroxide (448 g, 11.20 mol) in water (5.61 L). After stirring for 20 minutes at ambient temperature, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (3.65 L). The organic layers were combined, washed with brine (1.5 L), and concentrated under vacuum. The residue was treated with ethyl acetate (1.8 L) and heated to 65-70 C. The mixture was stirred at 65-70 C for 15 minutes to give a clear solution and then treated with n-heptane (7.3 L) maintaining the temperature between 60-70 C. Once the heptane was completely added to the solution, the mixture was held at 65-70 C for 15 minutes and then allowed to cool to 18- 22 C over 3 h. The resulting suspension was stirred at 18-22 C for 4 h, cooled to 0-5 C over 1 h, and held at 0-5 C for 2 h. The precipitate was filtered, washed twice with n-heptane (1.4 L), and dried under vacuum to give the title compound (540 g, 88%). The XRPD pattern of this compound is shown in Figure 17.

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; EPIZYME, INC.; EISAI R&D MANAGEMENT CO.LTD.; KUNTZ, Kevin, Wayne; HUANG, Kuan-chun; CHOI, Hyeong, Wook; SANDERS, Kristen; MATHIEU, Steven; CHANDA, Arani; FANG, Frank; WO2013/155317; (2013); A1;,
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Related Products of 924-99-2, A common heterocyclic compound, 924-99-2, name is Ethyl 3-(dimethylamino)acrylate, molecular formula is C7H13NO2, 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: All microwave reactions were carried out in a capped (10 mL) microwave-vessel (Borosilicate glass vial sealed) that was placed in a microwave cavity. The pressure was set at 17 bar (average of an effective pressure = 4 bar) with power 75 W. DIEA (3.4 g, 3.4 mmol) was added to a solution of either 2,5-difluoro-4-(pyrrolidin-1-yl) benzoylchloride 12 (0.83 g, 3.4 mmol) or 2,5-difluoro-4-(pyrrolidin-1-yl)benzothioyl chloride 13 (0.88 g, 3.4 mmol) and ethyl-3-(diethylamino)acrylate 14 (0.45 g, 3.1 mmol) in acetonitrile (5 mL). The mixture reaction was held at 100 C for 20 min. After the reaction vessel was cooled to room temperature, the crude product was diluted with water (10 mL) and extracted with ethyl acetate(3 ¡Á 10 mL). The organic layers were combined, dried over Na2SO4, filtered, evaporated and purified by a flash column chromatography (eluent n-hexane: acetone, 3:1)to give the titled compounds.

The synthetic route of 924-99-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Almashal, Faeza A.; Alshawi, Jasim M.; Dhumad, Adil M.; Jassem, Ahmed M.; Medicinal Chemistry Research; (2020);,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 176694-36-3, These common heterocyclic compound, 176694-36-3, name is Methyl 4-fluoro-3-(trifluoromethyl)benzoate, 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.

b N-tert-butoxycarbonyl-4-([4-methoxycarbonyl-2-methylsulfonyl)phenoxy]-phenylalanine benzyl ester 2.8 g of N-tert-butoxycarbonyl-tyrosine benzyl ester, 2.2 g of 4-fluoro-3-trifluoromethylbenzoic acid methyl ester and 4.0 g of K2 CO3 are stirred in 100 ml of DMF (anhydrous) at 110 C. for 45 minutes. The reaction mixture is poured into 500 ml of water, the pH is brought to 2 with NaHSO4 and the mixture is extracted 3 times with 200 ml of EA each time. The extract is dried over Na2 SO4 and the solvent is removed in vacuo. 4.2 g of a colorless oil. Rf (DIP)=0.12 MS (ES): 584 (M+H)+

Statistics shows that Methyl 4-fluoro-3-(trifluoromethyl)benzoate is playing an increasingly important role. we look forward to future research findings about 176694-36-3.

Reference:
Patent; Hoechst Aktiengesellschaft; US5631293; (1997); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics