Month: July 2021

3047-38-9, name is Cyclopent-1-enecarbonitrile, belongs to nitriles-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. name: Cyclopent-1-enecarbonitrile

Into a 5000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed 4-(benzyloxy)-lH-pyrazolo[4,3-c]pyridin-3-amine (1-1; 250 g, 1.04 mol), ethanol (3000 mL), cyclopent-l-ene-l-carbonitrile (300 g, 3.22 mol), and DBU (317 g, 2.08 mol). The resulting solution was heated to reflux and stirred overnight. The reaction mixture was cooled and concentrated in vacuo, and the resulting residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1 : 10-1 :2) to afford racemic-2-[3- amino-4-(benzyloxy)- lH-pyrazolo[4,3-c]pyridin- 1 -yljcyclopentane- 1 -carbonitrile. The racemic 2-[3-amino-4-(benzyloxy)- lH-pyrazolo[4,3-c]pyridin- 1 – yljcyclopentane- 1 -carbonitrile (100 g, 300 mmol) was purified using Chiral Prep-SFC with the following conditions: Column Used: Phenomenex Lux Cellulose-4, 2 x 25cm, 5 muiotaeta Mobile phase: C02 (80%), methanol with 0.1% DEA (20%) Wavelength: UV 254 nm. Peak A, 1-6: (lR,2R)-2-[3-amino-4-(benzyloxy)-lH-pyrazolo[4,3-c]pyridin-l-yl]cyclopentane- 1 -carbonitrile LRMS(ESI) calc’d for C19H20N5O [M+H] +: 334, found 334. 1H-NMR(300MHz, CDCI3): delta 7.86-6.84 (m, 7H), 5.55 (s, 2H), 4.94-4.86 (s, 2H), 4.49 (s, 1H), 3.34-3.26 (m, 1H), 2.39-2.01 (m, 6H). Peak B, 1-7: (llS’,2lS,)-2-[3-amino-4-(benzyloxy)-lH-pyrazolo[4,3-c]pyridin-l-yl]cyclopentane-l- carbonitrile LRMS(ESI) calc’d for C19H20N5O [M+H] +: 334, found 334. 1H-NMR(300MHz, CDCI3): delta 7.86-6.84 (m, 7H), 5.55 (s, 2H), 4.94-4.86 (s, 2H), 4.49 (s, 1H), 3.34-3.26 (m, 1H), 2.39-2.01 (m, 6H).

The synthetic route of 3047-38-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; CHILDERS, Matthew Lloyd; DINSMORE, Christopher; FULLER, Peter; GUERIN, David; KATZ, Jason David; PU, Qinglin; SCOTT, Mark E.; THOMPSON, Christopher F.; ZHANG, Hongjun; FALCONE, Danielle; TORRES, Luis; BRUBAKER, Jason; ZENG, Hongbo; CAI, Jiaqiang; DU, Xiaoxing; WANG, Chonggang; BAI, Yunfeng; KONG, Norman; LIU, Yumei; ZHENG, Zhixiang; WO2014/146490; (2014); A1;,
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Application of 3759-28-2, These common heterocyclic compound, 3759-28-2, name is 2-(Cyanomethyl)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.

100ml of water was added to the reaction vessel, 20mmol (o-cyanophenyl)acetonitrile, 40mmol of potassium (m-tolyl)trifluoroborate 0.4mmol palladium acetylacetonate, 0.8mmol nitrogen ligands L-1, and p-toluenesulfonic acid monohydrate 100mmol, in The reaction was stirred at 60 deg.] C for 30 hours.AntiAfter should be ended, the mixture was poured into ethyl acetate, sequentially with saturated NaHCO3solutionand brine, the aqueous layer was extracted with ethyl acetate, the organic layers combined (i.e., combined washedorganic layer and the extract obtained the organic layer), dried over anhydrous of Na2the SO4dried, vacuum is removed by evaporationof the solvent, the residue was purified by flash column chromatography (hexane / ethyl acetate, volume ratio of between1: 1) to give the target liquid product.The yield was 72.5%,% purity was 99.1(the HPLC).

The synthetic route of 3759-28-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wenzhou University; CHEN, JIUXI; LIU, MIAOCHANG; CHENG, TIANXING; WANG, XIAODONG; GAO, WENXIA; HUANG, XIAOBO; WU, HUAYUE; (14 pag.)CN104557701; (2016); B;,
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Adding a certain compound to certain chemical reactions, such as: 51762-67-5, name is 3-Nitrophthalonitrile, belongs to nitriles-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 51762-67-5, Safety of 3-Nitrophthalonitrile

3-Hydroxypthalonitrile was synthesized according to the literature method [22]. To a 50 mL round-bottom flask were added 3-nitropthalonitrile (2.0 g, 11.6 mmol), K2CO3 (1.8 g, 12.7 mmol) and NaNO2 (0.8g, 11.6 mmol) in DMSO (30 mL), and the reaction mixture was stirred under reflux for 30 min. After cooling to room temperature, the reaction mixture was diluted with water (90 mL) and subsequently acidified with 2M HCl to pH=3 to produce a precipitate. Then, the solid was collected by filtration and washed successively with water and methanol. The pure product was obtained by recrystallization in acetic acid as a brown crystal (0.8 g, 48%). Mp: 263-265C.

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; Chen, Wenqiang; Chen, Song; Zhou, Bingjiang; Wang, Hongbo; Song, Xiangzhi; Zhang, Hongyan; Dyes and Pigments; vol. 113; (2015); p. 596 – 601;,
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Application of 50846-36-1, 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. 50846-36-1, name is 2-Amino-2-methylpropanenitrile hydrochloride belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of 5-(6-ethoxy-2-(4-fluorophenyl)-3- (methylcarbamoyl)benzofuran-5-yl)-2-(methoxy-i)nicotinic acid (35 mg, 0.075 mmol) and 2-amino-2-methylpropanenitrile hydrochloride (9.03 mg, 0.075 mmol) in DMF (5.0 mL) at room temperature under a nitrogen atmosphere was added DIPEA (0.065 mL, 0.374 mmol). The mixture was cooled to 0C, and HATU (42.7 mg, 0.112 mmol) was added to the mixture. The reaction mixture was stirred at room temperature for 16 hr. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water, stirred for 5 min and the solid filtered. The crude product was purified by Prep HPLC to obtained the desired compound as a white solid. Yield: 11.50 mg, (28.79 %). PREPARATIVE HPLC: Column: Sunfire C-18(19* 150)mm*5um, Mobile Phase: 20mM Ammonium acetate pH 4.5 with acetic acid (A): MeCN (B), Flow: 18 ml/min, Rt: 10.74 min. NMR (400MHz, DMSO- de) delta ppm = 8.62 (s, 1 H), 8.50 (d, J= 2.4 Hz, 1 H), 8.44 (d, J= 4.6 Hz, 1 H), 8.23 (s, 1 H), 8.00 – 7.96 (m, 2 H), 7.58 (s, 1 H), 7.50 (s, 1 H), 7.41 – 7.36 (m, 2 H), 4.17 (q, J = 7.0 Hz, 2 H), 2.84 (d, J= 4.6 Hz, 3 H), 1.72 (s, 6 H), 1.32 (t, J= 6.9 Hz, 3 H). 19F NMR (376.6 MHz, DMSO-de) delta: -111.37. LCMS: (ES+) m/z = 534.4 (M+H)+, Column- Acentis Express C18 (50 x 2.1 mm; 2.7 um), Buffer : lOmM Ammonium Acetate pH-5 adjusted with HCOOH, Mobile phase A: Buffer : MeCN (95:5), Mobile phase B: Buffer : MeCN (5:95), Flow: 0.8 ml/min. Rt: 1.11 min, wavelength: 220nm. HPLC Method: SUNFIRE (150 X4.6mm) 3.5micron, Buffer: 0.05% TFA in water pH 2.5, Mobile Phase A: Buffer: MeCN (95:5), Mobile Phase B: MeCN: Buffer (95:5), Flow: 1.0 ml/min, Wavelength: 254 nm, Rt: 19.96 min, Wavelength: 220 nm, Rt: 19.96 min. HPLC Method: XBridge Phenyl (150 X4.6mm) 3.5micron SC/749, Buffer: 0.05% TFA in water pH 2.5, Mobile Phase A: Buffer: MeCN (95:5), Mobile Phase B: Buffer: MeCN (5:95), Flow: 1.0 ml/min, Wavelength: 254 nm, Rt: 16.94 min, Wavelength: 220 nm, Rt: 16.94 min.

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; YEUNG, Kap-Sun; KADOW, John F.; BORA, Rajesh Onkardas; ANJANAPPA, Prakash; GUPTA, Samayamunthula Venkata Satya Arun Kumar; (148 pag.)WO2016/137832; (2016); A1;,
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Application of 1735-53-1, 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. 1735-53-1 name is 4-Bromo-3-(trifluoromethyl)benzonitrile, 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.

The reaction was split into 4, using a quarter of the reagents in each: to a mixture of 4-bromo-3-(trifluoromethyl)benzonitrile (4 g, 16.00 mmol), phenylboronic acid (3.90 g, 32.0 mmol) and potassium carbonate (6.63 g, 48.0 mmol) in lambda/,lambda/-dimethylformamide (DMF) (64 ml) was added palladium tetrakistriphenylphosphine(O) (1.849 g, 1.600 mmol). Each reaction was heated in the microwave at 150 0C for 30 min. The combined reaction mixtures were filtered through celite, washed with ethyl acetate and the solvent removed in vacuo. The residue was partitioned between ethyl acetate (100 ml.) and water (100 ml.) and the organic phase washed with sodium bicarbonate solution (100 ml_). The organic phase was dried (MgSO4), filtered and the solvent removed in vacuo. The brown oil was triturated with dichloromethane and filtered to give a pale yellow solid, 2-(trifluoromethyl)-4-biphenylcarboxamide (2.47 g) which was used without further purification. To 2-(trifluoromethyl)-4- biphenylcarboxamide (2 g, 7.54 mmol) in ethanol (80 ml) was added potassium hydroxide (4.23 g, 75 mmol) and water and the mixture heated to 90 0C for 18 h. The reaction mixture was concentrated in vacuo and the residue partitioned between dichloromethane (100 ml.) and 2M HCI (100 ml_). The organic phase was isolated and dried (phase separator) and the solvent removed in vacuo to give the crude product. Purification using the Biotage Horizon, reverse phase cartridge, eluting 5- 100 % MeCN in water gave as an off-white solid the title compound (960 mg). MS (ES): C14H9F3O2 requires 266; found 265 (M-H+).

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

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/128951; (2008); A1;,
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Application of 52133-67-2,Some common heterocyclic compound, 52133-67-2, name is Ethyl 2-cyano-4,4-diethoxybutyrate, molecular formula is C11H19NO4, 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.

The compound (1) (30.0 g, 0.313 mol) was added to a suspension of sodium hydride (3.77 g, 0.617 mol) in dimethylformamide (100 ml) under nitrogen atmosphere below 20° C., and the mixture was stirred at room temperature for 30 min. To the resulting mixture was added 2-(3-chloropropyl)tetrahydro-2H-pyran (25.7 g, 0.144 mol) at the same temperature, then the mixture was stirred in an oil bath at 60° C. for 16 h. The reaction mixture is evaporated under reduced pressure to remove dimethylformamide, to the residue was added water and the mixture was extracted with toluene. After the toluene layer was washed with water, dried over magnesium sulfate, and evaporated to remove toluene, the excess of 2-(3-chloropropyl)tetrahydro-2H-pyran was distilled and removed in an oil bath at 150° C. under reduced pressure to give the compound (2) (41.5 g, 85.4percent). [00174] 1H NMR (CDCl3); 1.18 (3H, t, J=6.9 Hz), 1.21 (3H, t, J=6.9 Hz), 1.33 (3H, t, J=7.2 Hz), 1.52-2.04 (12H, m), 2.40 (1H, m), 3.39-3.86 (7H, m), 4.24 (2H, m), 4.57 (1H, m), 4.77 (1H, m).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Ethyl 2-cyano-4,4-diethoxybutyrate, its application will become more common.

Reference:
Patent; Shionogi & Co., Ltd.; US6756376; (2004); B1;,
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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. 69395-13-7, name is 4-(2-Hydroxyethyl)benzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 4-(2-Hydroxyethyl)benzonitrile

Preparation 5 Preparation of 4-carbamoylphenethyl bromide STR39 A solution of phosphorus tribromide (5 g) in carbon tetrachloride (10 ml) was added, dropwise, to a solution of 4-cyanophenethyl alcohol (8.06 g) in carbon tetrachloride (60 ml). The mixture was heated under reflux for 4 hours. On cooling to room temperature, the mixture was poured onto ice (200 g). The layers were separated and the organic layer was washed with 10% aqueous sodium carbonate (50 ml) and brine (50 ml), dried (MgSO4) and concentrated in vacuo to give a colourless oil which solidified on standing. The solid was chromatographed on silica eluding with ethyl acetate containing hexane (20%). The fractions containing the less polar (higher Rf) product were combined and concentrated in vacuo to give 4-cyanophenethyl bromide as a yellow oil which solidified on standing, yield 8.9 g. The fractions containing the more polar (lower Rf) product were combined and concentrated in vacuo to give the title compound as a colourless solid, yield 0.47 g, m.p. 152-153. 1 H N.m.r. (CDCl3)delta=7.85 (d, 2H); 7.35 (d, 2H); 6.20-5.70 (brd, 2H); 3.70-3.60 (m, 2H); 3.35-3.20 (m, 2H) ppm.

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 69395-13-7.

Reference:
Patent; Pfizer Inc; US5422358; (1995); A;,
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These common heterocyclic compound, 3672-47-7, name is 3-(4-Methoxyphenyl)-3-oxopropanenitrile, 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. Product Details of 3672-47-7

In a 15 mL reaction tube, add 1c (52.6 mg, 0.3 mmol), 1,2-dichloroethane (DCE, 1 mL), 2-methyl-4-phenyl-3-butyn-2-ol (2a , 72.1mg, 0.45mmol),Dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([RhCp * Cl2] 2, 13.0mg, 0.021mmol) and CsOAc (57.6mg, 0.3mmol) will react in the air atmosphere The tube was sealed and the reaction was stirred at 100 C for 24 h. After the reaction was completed, the reaction tube was cooled to room temperature, suction filtered, and the mother liquor was spin-dried with silica gel and separated through a silica gel column (petroleum ether / ethyl acetate = 10/1) to obtain 3c (61.8 mg, 65%) as a yellow solid.

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

Reference:
Patent; Henan Normal University; Fan Xuesen; Song Xia; Zhang Xinying; (24 pag.)CN110746319; (2020); A;,
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Some common heterocyclic compound, 6136-93-2, name is 2,2-Diethoxyacetonitrile, molecular formula is C6H11NO2, 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. Quality Control of 2,2-Diethoxyacetonitrile

Into a 100-mL round bottom flask was placed a solution of 2,2-diethoxyacetonitrile (5.00 g, 38.83 mmol) and sodium methylate(30% in methanol, 1 mL) in methanol (30 mL)at ambient temperature. The resulting mixture was degassed with nitrogen for3 times and stirred at room temperature for 42 hr. The reaction was quenched with solid CO2and evaporated under vacuum. The residue was diluted with water (100 mL) and extracted with dichloromethane (3 xlOO mL). The combined organics were washed with brine(200 mL),dried over anhydrous sodium sulfate and filtered. The solvent was evaporated under vacuum to yieldthe title compound:?H NMR (400 MHz, CD3C1): oe7.89 (s, 1H), 4.80 (s, 1H),3.81 (s, 3H), 3.60-3.52 (m, 4H), 1.29-1.22 (m, 6H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6136-93-2, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; BENNETT, Frank; JIANG, Jinlong; PASTERNAK, Alexander; DONG, Shuzhi; GU, Xin; SCOTT, Jack D.; TANG, Haiqun; ZHAO, Zhiqiang; HUANG, Yuhua; HUNTER, David; YANG, Dexi; ZHANG, Zhibo; FU, Jianmin; BAI, Yunfeng; ZHENG, Zhixiang; ZHANG, Xu; YOUNG, Katherine; XIAO, Li; (580 pag.)WO2016/206101; (2016); A1;,
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Application of 859855-53-1, 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. 859855-53-1 name is 3-Amino-4-fluorobenzonitrile, 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.

A solution of NaNO2 (380 mg, 5.51 mmol) in water (2 mL) was added to a suspension of 3-amino-4-fluorobenzonitrile (500 mg, 3.67 mmol) in concentrated HCl (5 mL) at 0 C over 5 mins., and the solution stirred for a further 30 mins. Meanwhile, AcOH (5 mL) was saturated with SO2, then CuCl2.2H2O (188 mg, 1.10 mmol) was added and SO2 bubbled through for a further 5 mins. The AcOH mixture was cooled to 5 C, then the diazonium solution added over 5 mins. The resulting mixture was stirred for a further 1h at 0 C then 1h at room temperature. The solution was diluted with water and extracted twice with CH2Cl2. The combined organic extracts were washed twice with water, dried (Na2SO4) and the solvent removed in vacuo. Chromatography (hexanes: EtOAc 19:1 to 9:1) gave the title compound as a yellow oil (569 mg, 71%). 1H NMR delta (400 MHz, CDCl3) 8.31 (dd, J 6.2, 2.1 Hz, 1H), 8.04 (ddd, J 8.7, 4.3, 2.1 Hz, 1H), 7.51 (t, J 8.7 Hz, 1H). LCMS (APCI-) 200 (M-Cl+O, 100%).

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

Reference:
Article; Kendall, Jackie D.; Giddens, Anna C.; Tsang, Kit Yee; Marshall, Elaine S.; Lill, Claire L.; Lee, Woo-Jeong; Kolekar, Sharada; Chao, Mindy; Malik, Alisha; Yu, Shuqiao; Chaussade, Claire; Buchanan, Christina; Jamieson, Stephen M.F.; Rewcastle, Gordon W.; Baguley, Bruce C.; Denny, William A.; Shepherd, Peter R.; Bioorganic and Medicinal Chemistry Letters; vol. 27; 2; (2017); p. 187 – 190;,
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