Tag: M.W=100-200

Application of 53312-82-6, A common heterocyclic compound, 53312-82-6, name is 4-Amino-2-bromobenzonitrile, molecular formula is C7H5BrN2, 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.

To a stirred mixture of 4-amino-2-bromobenzonitrile (2.00 g, 10.2 mmol), cyclopropyl boronic acid (1,18 g, 13.7 mmol) and K3PO4 (3.23 g, 15.2 mmol) in the mixed solvents of EtOH/H2O/toluene (2 mL/2 mL/12 mL) under nitrogen was added PdCl2(PPh3)2 (0.72 g, 1.03 mmol). This mixture was heated at 800C for 19 h and cooled to room temperature. Next, the mixture was diluted with 150 mL of EtOAc and filtered through a pad of silica gel topped with a layer of celite. This pad was further rinsed with EtOAc (2 x 100 mL). The filtrate was washed with 25 mL of brine, dried over MgSO4, filtered and concentrated in vacuo to give the crude amine. The crude amine was purified by an ISCO auto flash chromatographer using 12O g silica gel column, eluted with hexanes/CH2Cl2 solvents in a 25 min 50% to 100% gradient elution to give 0.75 g of Preparation 4OA as a white solid in 47% yield. [00428] HPLC: 1.55 min (RT) (Chromolith SpeedROD column 4.6 x 50 mm, 10- 90% aqueous MeOH over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z=159 [M+H]+. 1H NMR of 4-amino-2- cyclopropyl-benzonitrile (400 MHz, CDCl3) delta ppm 7.34 (d, J=8.31 Hz, 1 H) 6.44 (dd, J=8.31, 2.27 Hz, 1 H) 6.12 (d, J=2.01 Hz, 1 H) 4.01 (s, 2 H) 2.13-2.24 (m, 1 H) 1.02- 1.12 (m, 2 H) 0.68-0.76 (m, 2 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; BRISTOL-MYERS SQUIBB COMPANY; WO2009/3077; (2008); A1;,
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Reference of 4421-09-4, 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. 4421-09-4, name is 3,4-(Methylenedioxy)benzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Synthesis of 5-substituted-1H-tetrazoles (general procedure): To a solution of aryliodide (1 mmol) in DMF (5 ml) was added sodium cyanide (1.2 mmol), catalyst(10 mol %) and the reaction mixture was stirred under heating at 100 C for appropriate time to obtain nitrile compound (see Table 1). To the nitrile compound generated in situ was added sodium azide (1.5 mmol) and the reaction was continued till the complete conversion of nitrile to tetrazole. After the completion of the reaction, the catalyst from the reaction mixture was easily separated out by centrifuging the reaction mixture. After the separation of the catalyst the crude material was then taken into ethyl acetate and washed with 5 N HCl and the layers separated. The organic layer was then washed with water, dried over anhyd sodium sulfate and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography using appropriate solvent mixtures to obtain the pure products (see Tables 1 and 2). Detailed experimental conditions and spectroscopic data were given insupplementary data.

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

Reference:
Article; Yapuri, Umanadh; Palle, Sadanandam; Gudaparthi, Omprakash; Narahari, Srinivasa Reddy; Rawat, Dhwajbahadur K.; Mukkanti, Khagga; Vantikommu, Jyothi; Tetrahedron Letters; vol. 54; 35; (2013); p. 4732 – 4734;,
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Some common heterocyclic compound, 6393-40-4, name is 4-Amino-3-nitrobenzonitrile, molecular formula is C7H5N3O2, 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: nitriles-buliding-blocks

3-Nitro-4-aminobenzonitrile (3.00 g) was dissolved in ethanol (300 ml) and added with stannous chloride dihydrate (20.7 g) and the whole was heated to 60C. Sodium borohydride (348 mg) was gradually added thereto and the whole was stirred overnight at 60C. After completion of the reaction, the resultant was added with water (300 ml) and neutralized with a 5 mol/l sodium hydroxide aqueous solution. After ethanol was distilled off under reduced pressure, the aqueous layer was added with ethyl acetate for extraction. The organic layer was washed with a saturated saline solution and then dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was recrystallized, thereby obtaining the subject compound (1.11 g) as a brown crystal. MS(EI):m/z=133[M]+ 1H-NMR(500MHz,CDCl3):delta=6.68(1H,d,J=8,1Hz),6.95(1H,s),7.05(1H,d,J=8.1Hz).3-Nitro-4-amino-benzonitrile (4.38 g) was dissolved in ethanol (600 ml) and added with stannous chloride dihydrate (34.6 g) and the whole was heated to 60C. Sodium borohydride (366 mg) was gradually added thereto and the whole was stirred overnight at 60C. After completion of the reaction, the resultant was filtrated through Celite and the filtrate was subjected to distillation of the solvent under reduced pressure. The residue was dissolved in chloroform, washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, and then dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was allowed to recrystallize (hexane/ethyl acetate), thereby obtaining the subject compound (2.56 g) as a brown crystal. MS (EI) :m/z=133[M]+ 1H-NMR(500MHz,CDCl3):delta=6.68(1H,d,J=8.1Hz),6.95(1H,s),7.05(1H, d,J=8.1Hz).An ethanol solution (300 ml) containing 4-amino-3-nitrobenzonitrile (3.00 g) was added with stannous chloride dihydrate (20.7 g) and then added with sodium borohydride (348 mg) . The whole was stirred overnight at 60C. After that, the resultant was subjected to distillation until the amount of the solution became about 100 ml. The resultant was added with water (100 ml) and a large amount of solid component was generated. The resultant was added with a 5 mol/l sodium hydroxide aqueous solution (42 ml) to adjust to pH 7. The solvent was distilled off. The solid component was filtrated out through Celite and washed with methanol and ethyl acetate in the stated order. The filtrate was again filtrated through Celite and only organic solvent was distilled off under reduced pressure. The remaining aqueous layer was subjected to extraction with ethyl acetate and dried with anhydrous magnesium sulfate , and the solvent was distilled off, thereby obtaining the subject compound (2.29 g) as a khaki crystal.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6393-40-4, its application will become more common.

Reference:
Patent; Kureha Corporation; EP1724263; (2006); A1;,
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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 159847-81-1 as follows. category: nitriles-buliding-blocks

2-amino-5-cyanobenzoic acid. To a solution of methyl 2-amino-5- cyanobenzoate (0.120 g, 0.68 mmol) in THF (3.5 ml), was added a solution of lithium hydroxide (0.033 g, 1.36 mol, 2.0 eq) in H20 (3.5 ml). After stirring at rt for 3h, the reaction mixture was concentrated. The residue was diluted with H20 (5 ml) and acidified to pH~3 using 1M HCl. The precipitate was collected by filtration, washed with H20 and dried under air. 2-amino-5-cyanobenzoic acid (0.11 g, 95%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-de) delta 8.04 (d, J= 2.1 Hz, 1H), 7.70-7.33 (m, 3H), 6.86 (d, J= 8.8 Hz, 1H).

According to the analysis of related databases, 159847-81-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITY OF KANSAS; UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.; SOUTHERN RESEARCH INSTITUTE; GOLDEN, Jennifer; AUBE, Jeffrey; CHUNG, Donghoon; SCHROEDER, Chad; YAO, Tuanli; WHITE, E. Lucile; TOWER, Nichole A.; WO2014/93869; (2014); A1;,
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Related Products of 60702-69-4, 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. 60702-69-4, name is 2-Chloro-4-fluorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

1. Synthesis of tert-butyl N-[(1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamate Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl N-[(1r,3r)-3-hydroxy-2,2,4,4-tetramethylcyclobutyl]carbamate (600.0 mg, 2.47 mmol, 1.00 equiv) in N,N-dimethylformamide (10.0 mL). This was followed by the addition of sodium hydride (198.0 mg, 8.25 mmol, 2.00 equiv), in portions at 0 C. After 30 minutes, to this was added 2-chloro-4-fluorobenzonitrile (459.0 mg, 2.95 mmol, 1.20 equiv). The resulting solution was stirred for 1 hour at 70 C. The reaction mixture was cooled to room temperature with a water bath. The reaction was then quenched by the addition of water (20 mL). The resulting solution was extracted with ethyl acetate (20 mL*3) and the organic layers combined. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/5). This resulted in 100.0 mg (11%) of tert-butyl N-[(1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamate as colorless oil. LC-MS (ES+): m/z 279.10 [MH-100]+, tR=1.20 min (2.5 minute run).

The chemical industry reduces the impact on the environment during synthesis 2-Chloro-4-fluorobenzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Arvinas, Inc.; Crew, Andrew P.; Hornberger, Keith R.; Snyder, Lawrence B.; Zimmermann, Kurt; Wang, Jing; Berlin, Michael; Crews, Craig M.; Dong, Hanqing; (605 pag.)US2018/99940; (2018); A1;,
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Some common heterocyclic compound, 63069-50-1, name is 4-Amino-3-fluorobenzonitrile, molecular formula is C7H5FN2, 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. HPLC of Formula: C7H5FN2

Add in a 100mL two-necked flask4-chloro-7-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.5 g, 5.8 mmol),2-Fluoro-4-cyanoaniline (0.86 g, 6.3 mmol) and 20 mL of tetrahydrofuran, protected with nitrogen,The reaction flask was cooled to 0 C and 60% sodium hydride (0.46 g, 11.5 mmol) was slowly added.The reaction was then warmed to 65 C and stirred overnight.The reaction solution was extracted twice with ethyl acetate and twice with saturated sodium chloride.Dry over anhydrous sodium sulfate and evaporated to dryness under reduced vacuo.Purified by silica gel column chromatography(petroleum ether (PE): ethyl acetate (EA) = 1:1)0.7 g of a yellow solid was obtained in a yield of 35%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 63069-50-1, its application will become more common.

Reference:
Patent; Jiangxi University of Traditional Chinese Medicine; Yang Zunhua; Fang Yuanying; Jin Yi; Wang Qi; Ouyang Hui; Feng Yulin; (33 pag.)CN110256420; (2019); A;,
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Reference of 50397-74-5, 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 50397-74-5 as follows.

General procedure: Aniline 1 (0.5 mmol), H2O (5 mL), KOH (1 mmol, 2 equiv), and the CTAB (0.05 mmol, 10% mmol) were added to the reaction vessel stirring for 5 min. Allyl bromide (1 mmol, 2 equiv) was added, while maintaining the temperature at 80 C for 10 min under microwave irradiation (850 W). After completion of the reaction, the mixture was extracted with CH2Cl2 (3 × 15 mL). The combined organic layer was washed with brine (20 mL), dried over Na2SO4, and evaporated. The residue was purified by column chromatography (petroleum ether/ethyl acetate) to afford N-allylaniline 2a-j.

According to the analysis of related databases, 50397-74-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Liu, Meiyu; Wang, Xie; Sun, Xiaoliang; He, Wei; Tetrahedron Letters; vol. 55; 16; (2014); p. 2711 – 2714;,
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Synthetic Route of 222978-02-1, These common heterocyclic compound, 222978-02-1, name is 2-Fluoro-4-(hydroxymethyl)benzonitrile, 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.

To a solution of 2-fluoro-4-(hydroxymethyl)benzonitrile (400 mg, 2.65 mmol) and TEA (0.738 mL, 5.29 mmol) in DCM (10 mL) was added methanesulfonyl chloride ( 1.27 g, 11.1 mmol) at 0 C, and the reaction mixture was stirred for 16 h at 16 C. The reaction mixture was concentrated in vacuo to give 4-cyano-3-fluorobenzyl methanesulfonate as an oil. ESI-MS m/z [M + H]+: low ionization.

The synthetic route of 222978-02-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WALJI, Abbas; BERGER, Richard; STUMP, Craig, A.; SCHLEGEL, Kelly Ann, S.; MULHEARN, James, J.; GRESHOCK, Thomas, J.; WANG, Deping; FRALEY, Mark, E.; JONES, Kristen, G.; (273 pag.)WO2017/222951; (2017); A1;,
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Electric Literature of 654-70-6, 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. 654-70-6, name is 4-Cyano-3-trifluoromethylaniline, This compound has unique chemical properties. The synthetic route is as follows.

4-Amino-2-trifluoromethylbenzonitrile, (2.23 g, 12 mmol) was added portionwise over15 minutes into the well-stirred heterogeneous mixture of thiophosgene (1 ml, 13 mmol) in water (22 ml) at room temperature. Stirring was continued for an additional 1 h. The reaction medium was extracted with chloroform (3 x 15 ml). The combined organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure to yield desired product, 4-isothiocyanato-2-trifluoromethylbenzonitrile, (Ia), as brownish solid and was used as such for the next step (2.72 g, 11.9 mmol, 99%).

The chemical industry reduces the impact on the environment during synthesis 4-Cyano-3-trifluoromethylaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; WO2006/124118; (2006); A1;,
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Synthetic Route of 6393-40-4, 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. 6393-40-4 name is 4-Amino-3-nitrobenzonitrile, 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.

General procedure: A 100-mL round-bottomed single-neck flask equipped with a condenser and a magnetic stir bar was charged with appropriated 4-substituted-2-nitroaniline (25.0mmol), 2,5-dimethoxytetrahydofurane (25.0mmol) and 40mL of glacial acetic acid. The flask was refluxed until disappearance of starting material (ca. 2 h). After the reaction mixture was cooled to rt, removal of the volatiles under reduced pressure gave the crude product which was purified by column-chromatography (Petroleum Ether/EtOAc=9:1 then 7:3) to give the desired 1-(4-substituted-2-nitrophenyl)-1H-pyrrole.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Amino-3-nitrobenzonitrile, and friends who are interested can also refer to it.

Reference:
Article; Primas, Nicolas; Suzanne, Peggy; Verhaeghe, Pierre; Hutter, Sebastien; Kieffer, Charline; Laget, Michele; Cohen, Anita; Broggi, Julie; Lancelot, Jean-Charles; Lesnard, Aurelien; Dallemagne, Patrick; Rathelot, Pascal; Rault, Sylvain; Vanelle, Patrice; Azas, Nadine; European Journal of Medicinal Chemistry; vol. 83; (2014); p. 26 – 35;,
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