Author: Jessica.F

Synthetic Route of 64113-86-6, A common heterocyclic compound, 64113-86-6, name is 5-Methyl-2-nitrobenzonitrile, molecular formula is C8H6N2O2, 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.

5-Methyl-2-nitrobenzonitrile (1.92 g, 11.84 mmol) was added in portions to a stirred solution of SnCl2 (11.22 g, 59.2 mmol) in conc. HCl (12 mL) and EtOH (12 mL). The reaction temperature was maintained at 20-30 C. using an ice bath. The reaction mixture was then stirred at room temperature for 1 h and poured into an ice cold aqueous solution of NaOH (6N, app. 30 mL) to neutralize to pH7. The product was extracted into EtOAc, washed with brine, dried over MgSO4 and concentrated to provide the title product (1.56 g, 99%) as a yellow-brown solid. 1H NMR (400 MHz, DMSO-d6) delta 2.21 (s, 3H), 5.79 (bs, 2H), 6.68-6.71 (d, 1H), 7.10-7.13 (dd, 1H), 7.15 (s, 1H). 13C NMR (DMSO-d6) delta 20.13, 93.99, 116.12, 118.94, 125.38, 132.32, 135.76, 150.21. MS 133 (MH+).

The synthetic route of 64113-86-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SENOMYX, INC.; US2008/306053; (2008); A1;,
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Electric Literature of 17354-04-0, 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 17354-04-0 as follows.

General procedure: Piperidine (0.03 ml, 5 mol %) was added to a warm solution of the appropriate salicylaldehyde 5 (5 mmol) and 2-(4,5-dimethoxy-2-nitrophenyl)acetonitrile (1.12 g, 5 mmol) in EtOH (10 ml). The resulting solution was refluxed with stirring for 5 h. The mixture was treated with a solution of concentrated H2SO4 (0.55 ml) in EtOH (2 ml) and refluxed with stirring for 2 h. The obtained precipitate was filtered, washed with EtOH (10 ml), hot H2O (40 ml) and finally with EtOH (10 ml), and dried at 100 C.

According to the analysis of related databases, 17354-04-0, the application of this compound in the production field has become more and more popular.

Reference:
Article; Irgashev, Roman A.; Karmatsky, Arseny A.; Slepukhin, Pavel A.; Rusinov, Gennady L.; Charushin, Valery N.; Tetrahedron Letters; vol. 54; 42; (2013); p. 5734 – 5738;,
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Some common heterocyclic compound, 86770-80-1, name is 3,3-Difluorocyclobutanecarbonitrile, molecular formula is C5H5F2N, 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 86770-80-1

A solution of 3,3-difluorocyclobutane-l-carbonitrile (1 g, 8.54 mmol) in ethanol (15 mL) was treated with hydroxylamine (50% in water) (5.25 mL, 86.0 mmol) and stirred at 80 C for 3 h. The reaction mixture was allowed to cool and then concentrated in vacuo. The residue was partitioned between DCM (10 mL) and water (10 mL). The organic phase was separated, the aqueous phase was extracted with DCM (3 x 5 mL),. The product re-extracted with 1 : 1 IPA/CHCI3 (3 x 60 mL), organic separated and dried over sodium sulfate and concentrated in vacuo to afford the title compound as an orange gum (545 mg,42%). 1H NMR (500 MHz, DMSO-d6) delta 9.07 (s, 1H), 5.44 (s, 2H), 2.84 – 2.59 (m, 5H). LCMS (ES+) RT 0.25 min, 151.0 (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 86770-80-1, its application will become more common.

Reference:
Patent; UCB BIOPHARMA SPRL; ALEXANDER, Rikki, Peter; BRACE, Gareth, Neil; BROWN, Julien, Alistair; CALMIANO, Mark, Daniel; CHOVATIA, Praful, Tulshi; DELIGNY, Michael; GALLIMORE, Ellen, Olivia; HEER, Jag, Paul; JACKSON, Victoria, Elizabeth; KROEPLIEN, Boris; MAC COSS, Malcolm; QUINCEY, Joanna, Rachel; SABNIS, Yogesh, Anil; SWINNEN, Dominique, Louis, Leon; ZHU, Zhaoning; WO2015/86526; (2015); 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 138642-47-4 as follows. HPLC of Formula: C8H6BrNO

Step A: 1-(2-Bromo-5-methoxyphenyl)methanamine 2-Bromo-5-methoxybenzonitrile (10.0 g, 47.2 mmol) was dissolved in dry tetrahydrofuran (100 mL) in a flame-dried flask and cooled in an ice bath. A solution of borane in tetrahydrofuran (75 mL, 75 mmol, 1.0 M) was added dropwise over a period of 30 minutes. The reaction mixture was stirred overnight at rt, then quenched slowly with ice water and Na2CO3 (saturated aqueous solution). After removal of THF, the residue was extracted with large amounts of EtOAc three times. The combined organic layers were washed with water, dried, and concentrated to give the crude, which was purified by silica gel column chromatography to give the desired product as a white powder (3.65 g, 36%). LCMS for C8H10BrNO (M+H)+: m/z=216.9, 219.0.

According to the analysis of related databases, 138642-47-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INCYTE CORPORATION; US2010/190804; (2010); A1;,
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Synthetic Route of 38469-84-0,Some common heterocyclic compound, 38469-84-0, name is 5-Methoxy-2-nitrobenzonitrile, molecular formula is C8H6N2O3, 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.

2-Amino-5-methoxybenzonitrile: [0441] A 100 mL round bottom flask was charged with 5-methoxy-2- nitrobenzonitrile (1.7 g, 9.55 mmol), sodium dithionite (4.99 g, 29 mmol), water (15 mL) and EtOH (50 mL). The resulting mixture was heated at reflux for 1 h. Work-up: the reaction mixture was concentrated in vacuo to remove ethanol then extracted with EtOAc (50 mL). The organic layer was dried over anhydrous Na2S04 and concentrated in vacuo, to afford 1.4 g (quantitative) of the product as yellow oil. It was used in the next step without further purification.

The synthetic route of 38469-84-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KALYPSYS, INC.; BORCHARDT, Allen; DAVIS, Robert; BEAUREGARD, Clay; BECKER, Daniel; GAMACHE, Daniel; NOBLE, Stewart, A.; HELLBERG, Mark, R.; KLIMKO, Peter, G.; ZHIHAI, Qui; PAYNE, Joseph, E.; YANNI, John; WO2011/112731; (2011); A2;,
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874285-03-7, name is 3-Bromo-2-fluorophenylacetonitrile, 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. Safety of 3-Bromo-2-fluorophenylacetonitrile

1.17 g of (3-bromo-2-fluorophenyl)acetonitrile and 15 mLof anhydrous DMSO were placed under nitrogen in an oven-dried flask. 459 mg of sodium hydride (60% dispersion in oil) were added, and the mixture was stirred at room temperature for 1 hour. 0.86 g of 2-chloroethyl ether dissolved with 2 ml anhydrous DMSO was added, and the mixture was stirred at room temperature overnight. 0.65 ml_ of glacial acetic acid was added, and the reaction was diluted into ethyl acetate, extracted with water and 5% sodium chloride, dried over magnesium sulfate, filtered, concentrated, and purified by flash chromatography on silica. The product fractions were concentrated and vacuum dried to give 730 mg of product. GCMS (M) 283; 1 H NMR (400 MHz, DMSO-c/6) delta ppm 2.04 – 2.15 (m, 2 H) 2.17 – 2.25 (m, 2 H) 3.69 (td, J=12.08, 1.88 Hz, 2 H) 4.01 (dd, J=11.95, 2.82 Hz, 2 H) 7.27 (td, J=7.92, 1.07 Hz, 1 H) 7.47 – 7.55 (m, 1 H) 7.80 (ddd, J=8.12, 6.65, 1.61 Hz, 1 H).

The synthetic route of 874285-03-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; WO2009/69044; (2009); A1;,
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Synthetic Route of 64113-86-6, The chemical industry reduces the impact on the environment during synthesis 64113-86-6, name is 5-Methyl-2-nitrobenzonitrile, I believe this compound will play a more active role in future production and life.

A reaction product as prepared in Step 2 (84 g, 0.52 mol) was added to a solution of 4-methoxycarbonylbenzaldehyde (77.4 g, 0.47 mol) in tetrahydrofuran, and the mixture was stirred for 30 minutes at ambient temperature. 1,1,3,3-tetramethylguanidine (60.8 mL, 0.48 mol) was dissolved in THF (600 mL) and charged. The resulting mixture was stirred with heating at reflux for 4.5 days. The reaction was cooled to 25 C., and a mixture of AcOH (84 mL) and water (600 mL) was added drop-wise while stirring. The precipitate was filtered off and mixed with acetone (500 mL). the resulting solid was filtered off, washed with acetone, and dried to yield a yellow solid product (77.1 g, 53% yield). The overall reaction is shown below.

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, 5-Methyl-2-nitrobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Chelsea Therapeutics, Inc.; US2009/253719; (2009); 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. 175596-01-7, name is Methyl 4-cyano-2-fluorobenzoate, A new synthetic method of this compound is introduced below., SDS of cas: 175596-01-7

A mixture of methyl 4-cyano-2-fluorobenzoate (2) (1 .0 g, 5.6 mmol) and 50% (0607) aq. hydroxylamine (6.84 mL, 1 12 mmol) in EtOH (30 mL) was stirred at reflux for 18 h. The reaction mixture was cooled to RT, diluted with H20 (20 mL) and extracted with EtOAc (60 mL). The organic solution was washed with brine (100 mL), dried over MgS04, filtered and concentrated in vacuo to give methyl 2-fluoro-4-(//’- hydroxycarbamimidoyl) benzoate (3) (260 mg, 22%) as a 1 :1 mixture of methyl and ethyl esters that was progressed without purification: m/z 227, 213 [M+H]+ (ES+)

The synthetic route of 175596-01-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KING’S COLLEGE LONDON; BORTHWICK, Alan David; MILLS, Mark Trevor; BROWN, Jane Theresa; CORCORAN, Jonathan Patrick Thomas; DE CASTRO VASCONCELOS GONCALVES, Maria Beatriz; KALINDJIAN, Sarkis Barret; (161 pag.)WO2016/97004; (2016); A1;,
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57775-06-1, name is 2-(2-Bromophenyl)-2-methylpropanenitrile, 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. Recommanded Product: 2-(2-Bromophenyl)-2-methylpropanenitrile

To a solution of 2-(2- bromophenyl)-2-methylpropanenitrile (4.0 g, 17.8 mmol), in dry THF (40 mL) was added borane-dimethyl sulfide (5.08 mL, 53.5 mmol) at 0 °C and the reaction mixture was slowly brought to rt, stirred for 1 h and then, heated to reflux for 18 h. The solvent was removed and quenched with MeOH, and heated to reflux for 18 h. The reaction was concentrated and the residue was dissolved in EtOAc, washed with H2O, brine, dried (Na2SO4), flltered and concentrated to give 4.0 g of 103 A as a white solid. MS (ESI) m/z: 230.2 (M+H)+.

The synthetic route of 57775-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; ORWAT, Michael J.; PINTO, Donald J.P.; SMITH II, Leon M.; SRIVASTAVA, Shefali; WO2013/56034; (2013); A1;,
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Electric Literature of 133541-45-4, 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. 133541-45-4 name is 4-Bromo-2,5-difluorobenzonitrile, 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.

To a stirred suspension of 4-bromo-2,5-difluorobenzonitrile (91 g, 417 mmol) and potassium carbonate (173g, 1.25 mol) in N,N-dimethylformamide (910 ml) was added (S)-1,1,1-trifluoropropanol [CAS 3539-97-7] dropwise (52.4g, 460 mmol). The resulting mixture was heated at 70 C for for 15 hours and cooled to room temperature. The reactionwas concentrated and the residue was diluted with water. The aqueous solution was extracted with DCM (3x). Thecombined organic washes were washed with brine, dried over sodium sulfate, filtered, and concentrated under reducedpressure to give an oil (136.6 g). The residue was triturated with a mixture of hexanes and toluene (9:1, 200 mL) to givethe desired product as a white solid (90.3 g, 93% purity, 64% yield).LC-MS (Method A): Rt = 1.29 min; MS (ESIpos): m/z = 312.0 [M+H]+.1H-NMR (400 MHz, CHLOROFORM-d) delta [ppm]: 1.511 (4.41), 1.531 (15.64), 1.533 (16.00), 1.548 (15.84), 1.550 (15.83),4.566 (1.08), 4.581 (2.68), 4.597 (3.18), 4.612 (2.62), 4.626 (1.01), 7.194 (5.27), 7.207 (7.60), 7.220 (7.57).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-2,5-difluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; Bayer AG; Gradl, Stefan, Nikolaus; Niehues, Michael; Halfbrodt, Wolfgang; (43 pag.)EP3553052; (2019); A1;,
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