Month: June 2021

Reference of 4426-11-3, These common heterocyclic compound, 4426-11-3, name is Cyclobutanecarbonitrile, 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.

[00140] To a mixture of cyclobutanecarbonitrile (0.70 g, 8.6 mmol) and 2-chloro-6- fluorobenzoic acid (0.5 g, 2.9 mmol) in THF (9.6 mL) at 0 C was added KHMDS (0.5M in toluene, 12.6 mL, 6.3 mmol). The resulting mixture was heated at 70 C for 3h, then cooled down, concentrated in vacuo. The residue was taken up in 20mL H20, and extracted with Et^O for three times. The aqueous layer was acidified with 2N HC1, and extracted with CHCI3/1- PrOH (3: 1). The combined organics were dried over Na2SC>4, concentrated. The crude residue was used directly. MS: 236 (M+l). XH NMR (600 MHz, DMSO-d6): delta 12.9-13.1 (brs, 1H), 7.51 (dd, 1H, J= 8.4, 1.2Hz), 7.46 (t, lH, J= 8.4 Hz), 7.30 (dd, 1H, J= 8.4, 1.2 Hz), 2.56- 2.68(m, 4H), 2.22-2.32 (m, 1H), 1.84-1.90 (m, 1H).

The synthetic route of 4426-11-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LAPOINTE, Blair, T.; FULLER, Peter, H.; GUNAYDIN, Hakan; LIU, Kun; SCOTT, Mark, E.; TROTTER, B., Wesley; ZHANG, Hongjun; (211 pag.)WO2017/75182; (2017); 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. 96784-54-2, name is 3-Methyl-4-nitrobenzonitrile, A new synthetic method of this compound is introduced below., name: 3-Methyl-4-nitrobenzonitrile

C. To a stirred, 25 C. solution of 3-methyl-4-nitrobenzonitrile (24 g, 0.148 mol) in acetic acid (250 mL) under nitrogen was added dropwise a solution of SnCl2.2H2 O (133.57 g., 0.592 mol) in concentrated HCl (250 mL). After stirring for 3 hours, the reaction mixture was added carefully to excess cold ammonium hydroxide. The reaction mixture was extracted several times with ethyl ether. The organic extracts were then combined, dried (Na2 SO4) and evaporated under reduced pressure to afford 12 g (61%) of the title compound, 4-cyano-2-methylaniline, as a white solid; m.p. 64-66 C.

The synthetic route of 96784-54-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Syntex (U.S.A.) Inc.; US5034410; (1991); A;,
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Adding a certain compound to certain chemical reactions, such as: 118431-88-2, name is 3-Cyclopropyl-3-oxopropanenitrile, 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 118431-88-2, Application In Synthesis of 3-Cyclopropyl-3-oxopropanenitrile

COMPOUND 613: 2-cyano-1-cyclopropyl-3-[2-(ethylsulphonyl)phenyl]propan-1,3-dione, m.p. 169 C., starting from 3-cyclopropyl-3-oxopropanonitrile and 2-(ethylsulphonyl)benzoyl chloride.

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:
Patent; Rhone-Poulenc Agriculture Limited; US5804532; (1998); A;,
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Electric Literature of 154532-34-0,Some common heterocyclic compound, 154532-34-0, name is 3-(tert-Butyl)benzonitrile, molecular formula is C11H13N, 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 3-te/t-butylbenzonitrile (400 mg) in MeOH (5 mL), aqueous ammonium hydroxide (ImL) and Raney Nickel (catalytic) were added and the reaction mixture was hydrogenated at 50psi for 2h. Then the reaction mixture was filtered and solvent evaporated. (3-te/t-butylphenyl)methanamine was used without any purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-(tert-Butyl)benzonitrile, its application will become more common.

Reference:
Patent; COMENTIS, INC.; PURDUE RESEARCH FOUNDATION; WO2009/42694; (2009); A1;,
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Reference of 2469-99-0, 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. 2469-99-0 name is 3-Oxobutanenitrile, 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.

Step 1. 2-(2-Chlorobenzyl)-3-oxobutanenitrile Into a 250-mL 3-necked round-bottom flask, was placed ethanol (100 mL). This was followed by the addition of Na (1.72 g, 74.78 mmol, 1.50 equiv) in several batches. The reaction was refluxed until the Na dissolved. To this was added a solution of 3-oxobutanenitrile (4.15 g, 50.00 mmol, 1.00 equiv) in ethanol (20 mL) dropwise with stirring, while the temperature was maintained at reflux. The reaction was refluxed for 1 h. Then, a solution of 1-(bromomethyl)-2-chlorobenzene (10.25 g, 50.00 mmol, 1.00 equiv) in ethanol (20 mL) was added dropwise with stirring, while the temperature was maintained at reflux. Refluxing continued for 2 hrs. Then the reaction was cooled to room temperature, concentrated to dryness and then suspended between water and ether. The aqueous layer was separated and extracted with ether. The aqueous layer was acidified with 3N HCl to pH<6 and extracted with EA. The organic layer was dried over Na2SO4, filtered and concentrated to dryness. The residue was chromatographed (PE:EA=1:50) to get 2.9 g (27%) of 2-(2-chlorobenzyl)-3-oxobutanenitrile as a colorless oil. At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Oxobutanenitrile, and friends who are interested can also refer to it. Reference:
Patent; BIOENERGENIX; US2012/277224; (2012); A1;,
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Some common heterocyclic compound, 124289-21-0, name is 3-Bromo-5-methylbenzonitrile, molecular formula is C8H6BrN, 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. COA of Formula: C8H6BrN

In a vial fitted with a stir bar was placed 3-bromo-5-methyl-benzonitrile (266 mg, 1.357 mmol), 1-(3,5-difluorophenyl)-1,2,4-triazol-3-amine (205 mg, 1.045 mmol), sodium tert-butoxide (106 mg, 1.103 mmol), and chloro(2-di-t- butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl)[2-(2- aminoethyl)phenyl]palladium(II) (t-BuXPhos Palladacycle) (30 mg, 0.04607 mmol). tert-Butanol (5 mL) was added and the vial was sealed and purged with nitrogen. The mixture was heated to 80 C overnight. The reaction was extracted with ethyl acetate and washed with water. The organics were treated with MP-TMT (ca 100 mg) and refluxed for 4 hours, to capture residual palladium. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure to give crude 3-[[1-(3,5-difluorophenyl)-1,2,4-triazol-3-yl]amino]-5-methyl-benzonitrile (0.35 g of 90% purity, 97%). A small sample of crude material was crystalized from acetonitrile to give analytically pure 3-[[1-(3,5-difluorophenyl)-1,2,4-triazol-3-yl]amino]-5-methyl-benzonitrile. MR (300 MHz, DMSO-d6) delta 9.94 (s, 1H), 9.21 (s, 1H), 7.84 (s, 1H), 7.76 – 7.52 (m, 3H), 7.38 – 7.20 (m, 1H), 7.15 (s, 1H), 2.35 (s, 3H) ppm. ESI- MS m/z calc. 31 1.09827, found 312.15 (M+l)+; Retention time: 0.95 minutes

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 124289-21-0, its application will become more common.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; BETHIEL, Randy Scott; CAO, Jingrong; COLLIER, Philip, N.; DAVIES, Robert J.; DOYLE, Elisabeth; FRANTZ, James Daniel; GOLDMAN, Brian Anthony; GREY, Ronald Lee; GRILLOT, Anne-laure; GU, Wenxin; KOLPAK, Adrianne Lynne; KRAUSS, Paul Eduardo; LIAO, Yusheng; MAGAVI, Sanjay Shivayogi; MESSERSMITH, David; PEROLA, Emanuele; RYU, Elizabeth, Jin-Sun; SYKEN, Joshua; WANG, Jian; (491 pag.)WO2018/106646; (2018); A1;,
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Synthetic Route of 873-74-5, The chemical industry reduces the impact on the environment during synthesis 873-74-5, name is 4-Aminobenzonitrile, I believe this compound will play a more active role in future production and life.

Step 1: To a stirred solution of 4-aminobenzonitrile (10.0 g, 84.7 mmol) in MeCN (100 mL) at 90 C was slowlyadded N-chlorosuccinimide (12.4 g, 93 mmol). After the addition of N-chlorosuccinimide, the reaction mixture was stirredat 90 C for 2 h. The reaction mixture was then cooled to rt and concentrated under reduced pressure. The residue wasdissolved in 500 mL of CH2Cl2 and washed with 5% aq NaOH. The organic layer was dried over MgSO4 and concentratedunder reduced pressure to give 4-amino-3-chlorobenzonitrile as a tan solid (12.2 g, 95%). 1H NMR (300 MHz, CDCl3)delta 7.54 (d, J= 1.7 Hz, 1H), 7.35 (dd, J= 1.8, 8.4 Hz, 1H), 6.77 (d, J = 8.5 Hz, 1H), 4.63 (br s, 2H).

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, 4-Aminobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Ambit Biosciences Corporation; HADD, Michael J.; HOCKER, Michael D.; HOLLADAY, Mark W.; LIU, Gang; ROWBOTTOM, Martin W.; XU, Shimin; (299 pag.)EP2766359; (2016); B1;,
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Related Products of 50846-36-1,Some common heterocyclic compound, 50846-36-1, name is 2-Amino-2-methylpropanenitrile hydrochloride, molecular formula is C4H9ClN2, 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 M Lithium hydroxide (175 mL, 350 mmol, 10 equiv) was added to a solution of compound 27 (17.1 g, 35 mmol, 1 equiv) in THF (350 mL). The reaction mixture was stirred overnight at room temperature, at which point LC/MS indicated all the starting (0509) material was consumed. In addition to the desired product, ~20% of compound 28(b) (loss of benzenesulfonyl group) was also present. The reaction was poured into 1N HCl (0.5 L) and extracted with ethyl acetate (1 L). The organic layer was separated and concentrated under reduced pressure to give a crude mixture of compound 28(b) and compound 28(a), which were used subsequently. [0250] Step 5 – N-(2-Cyanopropan-2-yl)-6-(2-(6-fluoropyridin-3-yl)-1-(phenylsulfonyl)- 1H-pyrrolo[2,3-b]pyridin-5-yl)picolinamide (30): N,N’-diisopropylethylamine (14.1 mL, 81 mmol, 4 equiv) was added to a solution of the ~1 to 4 mixture of compound 28(b) and compound 28(a) (9.6 g, 20.23 mmol, 1 equiv) in DMF (135 mL). 2-Amino-2- methylpropanenitrile hydrochloride (3.7 g, 30.4 mmol, 1.5 equiv) was added and the reaction was stirred for ~30 minutes at room temperature. Propylphosphonic anhydride (T3P, 50 wt% in ethyl acetate) (23.8 mL, 40.5 mmol, 2 equiv) was added dropwise, with the internal temperature gradually increasing from 20 to 30 C during the addition. After stirring overnight, LC/MS indicated ~50% conversion of starting material. Stirring an additional 24 hours resulted in no further conversion. The reaction mixture was poured into water (1 L) and extracted with ethyl acetate (500 mL). The organic layer was separated, washed with saturated brine (500 mL) and concentrated under reduced pressure. The crude solid was dissolved in THF, dry-loaded onto silica gel and purified on an AnaLogix column (80 g), eluting with a gradient of 0 to 50% ethyl acetate in dichloromethane. The resulting solid was triturated with MTBE (15 mL) to give N-(2- cyanopropan-2-yl)-6-(2-(6-fluoropyridin-3-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5- yl)picolinamide.

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

Reference:
Patent; PLEXXIKON INC.; ZHANG, Chao; WU, Guoxian; SPEVAK, Wayne; GUO, Zuojun; ZHANG, Ying; (138 pag.)WO2018/226846; (2018); A1;,
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Adding a certain compound to certain chemical reactions, such as: 2698-41-1, name is 2-(2-Chlorobenzylidene)malononitrile, 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 2698-41-1, Safety of 2-(2-Chlorobenzylidene)malononitrile

General procedure: A mixture of 1,3-indandione (0.153 g, 1.05 mmol), 2 (1 mmol), iodine (0.304 g, 1.2 mmol) and DMAP (0.366 g, 3 mmol) was stirred in CH3CN at 40 C. After stirring until conversion was completed, the reaction mixture was partioned between water and ethyl acetate. The aqueous layer was extracted three times with ethyl acetate (3 x 15 mL). The resulting organic layer was washed with 10% NaHSO3 (2 x 15 mL) and then dried over sodium sulfate. After concentration, the crude products 3a – 3n were purified by flash column chromatography

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(2-Chlorobenzylidene)malononitrile, and friends who are interested can also refer to it.

Reference:
Article; Huang, Jiamin; Liu, Wenli; Wang, Changqing; Yang, Liu; Cao, Xiaohua; Tetrahedron Letters; vol. 61; 4; (2020);,
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Application of 34916-10-4, A common heterocyclic compound, 34916-10-4, name is 4-Oxo-cyclohexanecarbonitrile, molecular formula is C7H9NO, 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.

A mixture of 4-cyano-cyclohexanone (0.48 g, 3.9 mmol) and phenylhydrazine hydrochloride (0.42 g, 3.9 mmol) in glacial acetic acid (5 ml) is stirred at reflux for 1 h. The solvent is evaporated and the residue chromatographed on silica gel (heptane / EtOAc 2:1) to deliver the title compound as a brownish solid (158 mg) in 50% yield. tR (LC-5) 0.91 min; ESI-MS (positive ion): m/z 197.10 [M+H]+ (calcd 196.25 for C13Hi2N2). 1H-NMR (CDCl3): 2.25 (m, 2H); 2.96 (m, 5H); 7.14 (m, 2H); 7.30 (d, J=7.7 Hz, IH); 7.45 (d, J=7.1 Hz, IH); 7.79 (br s, IH).

The synthetic route of 34916-10-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ACTELION PHARMACEUTICALS LTD; WO2006/70325; (2006); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts