Category: nitriles-buliding-blocks

19472-74-3, A common heterocyclic compound, 19472-74-3, name is 2-Bromophenylacetonitrile, molecular formula is C8H6BrN, 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.

Example 33A A round bottom flask was charged under inert atmosphere with copper iodide (760 mg, 4 mmol), cesium carbonate (3.91 g, 12 mmol) then dimethylformamide (20 mL), previously degassed, was added followed by 2-Bromophenylacetonitrile (519 muL, 4 mmol), 3-Methylpyrazole (3.32 mL, 40 mmol) and N-N’-dimethylethylenediamine (425.86 muL, 4 mmol). The reaction mixture was heated to 120 C. for 2.5 hours. After cooling the reaction mixture was filtered through a Celite pad that was rinsed with dimethylformamide. The volume was reduced under reduced pressure, saturated ammonium chloride aqueous solution was added and extracted with ethyl acetate. The organic phase was washed with saturated aqueous NH4Cl solution, brine then dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography on SiO2 using cyclohexane/ethyl acetate mixture of increasing polarity (from 100% cyclohexane to 100% ethyl acetate) as eluant. The oil obtained was further purified by SPE cartridge Stratosphere ?PL-THIOL MP? to remove copper salts. 300 mg of the title compound (38%) were obtained.GC-MS (Method 3A.1): Rt: 10.47 minMS: 197 [M]+.

The synthetic route of 19472-74-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2012/115863; (2012); A1;,
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Adding some certain compound to certain chemical reactions, such as: 94087-40-8, name is 3-Chloro-2-fluorobenzonitrile, 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 94087-40-8. 94087-40-8

General procedure: An oven-dried round bottomed flask (50 mL capacity) equipped with a magnetic stir bar was evacuated and purged with argon. 2-Aminopyridine (1 mmol, 1 euiv), 2-fluorobenzonitrile (1.2 mmol, 1.2 euiv), KtOBu (4 mmol, 4 euiv) and DMSO (5 mL) were added successivelyat room temperature and the reaction mixture was allowed to stir at room temperature for 12 h. Water (10 mL) was added to the reaction mixture and the organic layer was extracted with ethyl acetate (2¡Á20 mL). The combined organic phases were washed with brine and dried over sodium sulfate. The solvent was removed and the residue was purified by column chromatography on silica gel using hexanes/ethyl acetate as an eluent.

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 3-Chloro-2-fluorobenzonitrile.

Reference:
Article; Sen, Tejosmita; Neog, Kashmiri; Sarma, Sangita; Manna, Prasenjit; Deka Boruah, Hari Prasanna; Gogoi, Pranjal; Singh, Anil Kumar; Bioorganic and Medicinal Chemistry; vol. 26; 17; (2018); p. 4942 – 4951;,
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78473-00-4,Some common heterocyclic compound, 78473-00-4, name is 4-Amino-3,5-dichlorobenzonitrile, molecular formula is C7H4Cl2N2, 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.

1-(3,5-difluoropyridin-4-yl)but-2-yn-1-one (7.86 g, 43.4 mmol) and 4-amino-3,5-dichlorobenzonitrile (9.74 g, 52.1 mmol) were dissolved in DCM (174 ml) and the mixture was treated with BF3*OEt2 (16.50 ml, 130 mmol). The reaction mixture was stirred at 50 C. overnight. The next day it was quenched via a slow addition to a saturated. NaHCO3 solution. Some MeOH was used for complete dissolution and transfer of the reaction mixture. The mixture was extracted with DCM (3*). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (10-100% EtOAc in heptane) to give the title compound (10.05 g, 55.7% yield). ESI-MS m/z: 368.0 [M+H]+ (Rt=1.43 min, LC-method 2)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Amino-3,5-dichlorobenzonitrile, its application will become more common.

Reference:
Patent; NOVARTIS AG; BARBE, Guillaume; BEBERNITZ, Gregory Raymond; GENG, Sicong; GULGEZE EFTHYMIOU, Hatice Belgin; LIAO, Lv; MA, Fupeng; MO, Ruowei; PARKER, David Thomas; PENG, Yunshan; PEUKERT, Stefan; YAMADA, Ken; YASOSHIMA, Kayo; (78 pag.)US2018/111932; (2018); A1;,
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16532-79-9, Adding some certain compound to certain chemical reactions, such as: 16532-79-9, name is 4-Bromophenylacetonitrile, 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 16532-79-9.

Under nitrogen atmosphere, a mixture of (4-(diphenylamino)phenyl)boronic acid (1.74 g, 6 mmol), 2-(4-bromophenyl)acetonitrile (0.98 g, 5mmol), Pd(PPh3)4 (0.065 g, 0.06 mmol), Na2CO3 (2.0 M, 3.0 mL), and toluene (50 mL)/THF (30 mL) was stirred at 90 C for 24 h. After it was cooled to room temperature, CHCl3 (100 mL) was added to the mixture. The organic portion was separated and washed with brine before dried over anhydrous MgSO4. The solvent was evaporated off, and the solid residues were purified by column chromatography to afford 1.26 g of 2 (green powder) with a yield of 69.9%. FTIR (KBr): upsilon = 2949 cm-1, 2230cm-1, 1595 cm-1, 1523 cm-1, 1490 cm-1, 1080 cm-1 1H NMR (500MHz, CDCl3): delta (ppm) 7.60 (2H, d, J = 8.5 Hz, H in phenyl), 7.47 (2H, d, J = 8.5 Hz, H in phenyl), 7.40 (2H, d, J = 8.0 Hz, H in phenyl), 7.30 (4H, t, J = 7.5 Hz, H in phenyl), 7.16 (6H, d, J = 8.5 Hz, H in phenyl), 7.07 (2H, t, J = 7.5 Hz, H in phenyl), 3.80 (2H, s, H in methylene). 13C NMR(125 MHz, CDCl3): delta (ppm) 147.59, 140.59, 133.89, 129.32, 128.34, 128.25, 127.68, 127.27, 124.56, 123.71, 123.11, 117.82, 23.31. HRMS m/z: Found 361.1695 [M+H]+; molecular formula C26H21N2 requires361.1699 [M+H]+.

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 16532-79-9.

Reference:
Article; Cao, Feng; Li, Chengjian; Lv, Chunyan; Ouyang, Mi; Pan, Guoxiang; Sun, Jingwei; Yang, Shengchen; Zhang, Cheng; Zhang, Yujian; Zhuo, Chaozheng; Dyes and Pigments; vol. 180; (2020);,
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Adding a certain compound to certain chemical reactions, such as: 2032-34-0, name is 3,3-Diethoxypropanenitrile, 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 2032-34-0, 2032-34-0

a) 7-bromoquinoline-3 -carbonitrileA mixture of 3,3-diethoxypropanenitrile (1.801 mL, 12.00 mmol),2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol) and p-toluenesulfonic acid monohydrate (0.380 g, 2.000 mmol) in toluene (30 mL) was heated under reflux using Dean-Starkapparatus for 3 h. The reaction was cooled, evaporated under reduced pressure, and the residue was dissolved in a small amount of DMF, diluted with chloroform, and washed with aq. NaHCO3 solution. The aqueous layer was extracted with chloroform, and the combined extracts were washed with brine, dried (Na2504), and concentrated in vacuo. Purification by flash chromatography (0-3% methanol in dichloromethane) followed by trituration in diethylether provided the title compound (1.75 g, 75%). ?H NMR (400 MHz, DMSO-d6) oe ppm7.95 (dd, J8.72, 1.89 Hz, 1 H) 8.08 (d, J8.84 Hz, 1 H) 8.38 (d, J2.02 Hz, 1 H) 9.13 (d, J1.52 Hz, 1 H) 9.21 (d, 1 H).

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, 3,3-Diethoxypropanenitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXOSMITHKLINE LLC; ADAMS, Nicholas, David; KIESOW, Terence, John; WIGGALL, Kenneth; WO2013/177253; (2013); A2;,
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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. 67515-59-7, name is 4-Fluoro-3-(trifluoromethyl)benzonitrile, A new synthetic method of this compound is introduced below., 67515-59-7

4-fluoro-3-(trifluoromethyl)benzonitrile (1 equiv) and the alcohol (1 equiv) were added to a microwave vial and cooled in an ice bath, then 0.5M potassium tert- butoxide in tetrahydrofuran (1.1 equiv) was carefully added and allowed to warm to room temperature. The contents were then heated to 115 C for 1 minute in the microwave. After cooling, celite was added and the solvent was removed under reduced pressure. The resulting powder was subjected to flash chromatography on silica gel.

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; LYNCH, Kevin; SANTOS, Webster; (353 pag.)WO2016/54261; (2016); A1;,
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The chemical industry reduces the impact on the environment during synthesis 52133-67-2, name is Ethyl 2-cyano-4,4-diethoxybutyrate, I believe this compound will play a more active role in future production and life. 52133-67-2

To the 250 mL round bottomed flask containing 14.2 g (61.8 mmol) of ethyl 2,2-diethoxy cyanoacetate was added 110 mL of absolute ethanol followed by 28 mL of sodium ethoxide (21percent, 75.0 mmol). Thiourea (5.7 g, 74.5 mmol) was added all at once and the mixture was heated to 95¡ãC and refluxed overnight. The mixture was then cooled to room temperature and concentrated. Water (250 mL) was added and the aqueous layer was washed with diethyl ether (3 x 250 mL). The aqueous layer was then neutralized with acetic acid (1 eq.) and the precipitate was filtered. The yellow solid was dried under vacuum over P2O5 overnight to give 9.2 g (35.5 mmol, 57percent) of crude product. 1H-NMR (DMSO, 600 MHz): sigma 1.07 (t, 6H, J = 7.2 Hz), 2.43 (d, 2H, J = 5.4 Hz), 3.37 – 3.43 (m, 6H), 3.56 – 3.61 (m, 2H), 4.50 (t, 1H, J = 5.4 Hz), 6.07 (s, 2H), 11.5 (br s, 1H), 11.7 (br s, 1H). 13C-NMR (DMSO, 150 Mz): sigma 15.4, 27.9, 61.9, 85.7, 101.7, 151.9, 161.8, 172.9. HRMS (FAB): expected for C10H18N3O3S (M+H)+: 260.10634. Found: 260.10640. IR(neat): vmax 3342, 3219, 2973, 2879, 1563 cm-1.

The chemical industry reduces the impact on the environment during synthesis 52133-67-2. I believe this compound will play a more active role in future production and life.

Reference:
Article; Kim, Jiae; Wang, Ligong; Li, Yongfeng; Becnel, Kimberlynne D.; Frey, Kathleen M.; Garforth, Scott J.; Prasad, Vinayaka R.; Schinazi, Raymond F.; Liotta, Dennis C.; Anderson, Karen S.; Bioorganic and Medicinal Chemistry Letters; vol. 22; 12; (2012); p. 4064 – 4067;,
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Some common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, molecular formula is C20H23FN2O2, 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. 103146-25-4

Oxalate [(+-)-Diol Oxalate Salt] (+-)-Diol compound (VI) (7 g, 0.0205 mol) and oxalic acid dihydrate (2.83 g, 0.0225 ml) were added to isopropyl alcohol (77 ml) and heated the contents to 75-80 C. to obtain a clear solution. The obtained solution was cooled to 10-15 C. and stirred for 2 h to complete the crystallization. The product was filtered, and thereafter dried at 50-60 C. under reduced pressure for 6 h to give 8.6 g of diol oxalate salt (VIa), with HPLC purity of 99.94%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 103146-25-4, its application will become more common.

Reference:
Patent; Kaushik, Vipin Kumar; Mohammed, Umar Khan; Meenakshisunderam, Sivakumaran; US2009/99375; (2009); A1;,
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These common heterocyclic compound, 134521-16-7, name is 4,4′-Dicyanobenzhydrol, 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. 134521-16-7

EXAMPLE 1 This example demonstrates a method for preparing bromo-bis-(4-cyanophenyl)-methane. A three-necked round-bottom flask equipped with a mechanical stirrer, a nitrogen inlet and a Dean Stark apparatus was charged with bis-(4-cyanophenyl)-methanol (60 g, 0.256 mole) and toluene (360 ml) and the reaction mixture was heated to 60 C. HBr (48%, 54 ml, 1.8 eq.) was added in one portion and the reaction mixture was refluxed for two hours, during which time water was removed by azeotropic distillation. The reaction mixture was cooled to 70 C., water was added (250 ml), and stirring was maintained for 5 minutes. The two resulting layers were separated, the aqueous phase was washed with toluene (50 ml), and the organic layers were combined and washed with an aqueous solution of 5% potassium carbonate (200 ml), then with water (250 ml). Toluene was distilled off under reduced pressure (about 290 ml) and the solution was cooled to 40 C. Hexane was added (240 ml) and the mixture was cooled to room temperature and stirring was maintained for about 18 hours. The crude solid product was obtained by filtration (70.3 g) in 92% yield, having a purity of 99% (by HPLC).

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 134521-16-7.

Reference:
Patent; CHEMAGIS LTD.; US2007/112202; (2007); A1;,
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19179-31-8, 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 19179-31-8 as follows.

Synthesis of Intermediate (1)(1 )Molecular Weight: 163.17 Molecular Weight: 197.3[00378] In a 3-neck 100 mL round-bottomed flask, 3,5-dimethoxy benzonitrile (10.0 g, 1 eq.), NaSH H20 (9.43 g, 2.0 eq.) and MgCl26H20 (12.43 g, 1.0 eq.) were dissolved in DMF (100 mL, 10 Vol.). The reaction mixture was stirred at room temperature for 2 h. Reaction completion was monitored on TLC using ethyl acetate: n-hexane (2:8)as mobile phase. Reaction mixture was brought to room temperature and quenched into the ice-water slurry (100 mL) and compound was extracted in the ethyl acetate (50 mL x 3). Organic layer was washed with brine solution (50 mL x 3) followed by drying using anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure to afford 2.5 g of crude compound, yield (20.68 %). Mass/LCMS: 197.0 NMR: Confirmed.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 19179-31-8, and friends who are interested can also refer to it.

Reference:
Patent; KARYOPHARM THERAPEUTICS, INC.; SHECHTER, Sharon; KAUFFMAN, Michael; SANDANYAKA, Vincent, P.; SHACHAM, Sharon; WO2011/109799; (2011); A1;,
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