Month: December 2020

Related Products of 3939-09-1, 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. 3939-09-1 name is 2,4-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 mixture of 2,4-difluorobenzonitrile (10.0 g, 72 mmol) and 1,1-dioxo-1?6-[1,2]thiazin-2-ane (8.84 g, 65.4 mmol) in 1:1 tetrahydrofuran/dimethylformamide (40 mL) was added potassium carbonate (9.0 g, 65.4 mmol). The mixture was stirred at 90 C. for 18 h then filtered and concentrated. The residue was purified by flash chromatography (SiO2) eluting with 10%-50% ethyl acetate/hexanes followed by recrystallization from hot ethyl acetate/hexane to give the title compound as white needles (0.537 g, 3% yield). 1H NMR (500 MHz, CD3OD) ? ppm: 7.70 (1H, dd, J=8.8, 5.8 Hz), 7.30 (1H, dd, J=8.8, 2.4 Hz), 7.15-7.12 (1H, m), 3.27 (2H, t, J=5.3 Hz), 3.33 (2H, t, J=6.1 Hz), 2.40-2.35 (2H, m), 2.05-2.01 (2H, m). LCMS (M+H) calcd for C11H16N2OF: 255.06; found: 255.19.

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

Reference:
Patent; Naidu, B. Narasimhulu; Banville, Jacques; Beaulieu, Francis; Connolly, Timothy P.; Krystal, Mark R.; Matiskella, John D.; Ouellet, Carl; Plamondon, Serge; Remillard, Roger; Sorenson, Margaret E.; Ueda, Yasutsugu; Walker, Michael A.; US2005/267105; (2005); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 13388-75-5, A common heterocyclic compound, 13388-75-5, name is 2-(3,5-Dimethoxyphenyl)acetonitrile, molecular formula is C10H11NO2, 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 487 Preparation of the intermediate 5-bromo-3-(3,5- dimethoxy-phenyl)-pyrazolo[1 ,5-a]pyrimidineExample 487a Preparation of 2-(3,5-dimethoxy-phenyl)-3- dimethylamino-acrylonitrileA mixture of (3,5-dimethoxy-phenyl)-acetonitrile (19.9 g, 112 mmol), N,N,N’,N’-tetramethyl-ethane-1 ,2-diamine (2.86 mL, 19.09 mmol) and dimethyl formamide dimethyl acetal (72 mL) were heated at reflux for 4 h. On cooling, the reaction was partitioned between EtOAc and saturated aqueous ammonium chloride solution, and the mixture filtered, and the residue washed with EtOAc and dried to give 2-(3,5-dimethoxy-phenyl)-3- dimethylamino-acrylonitrile (7.1 g, 27%). The filtrates were combined, extracted and the combined organic phase washed with brine and concentrated in vacuo. The crude product was purified by chromatography on silica gel to give 2-(3,5-dimethoxy-phenyl)-3-dimethylamino-acrylonitrile (11.1 g, 43%). 1H-NMR (300 MHz, d6-DMSO): delta = 7.44 (1H, s), 6.42 (2H, d), 6.20 (1 H, t), 3.69 (6H, s), 3.15 (6H, s) ppm.

The synthetic route of 13388-75-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER SCHERING PHARMA AKTIENGESELLSCHAFT; WO2007/147647; (2007); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 7357-70-2, name is 2-Cyanothioacetamide belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 2-Cyanothioacetamide

To a suspension of 3-(l,2-dimethyl-lH-imidazol-5-yl)-l-(thiazol-2- yl)prop-2-en-l-one (0.31 mmol, 72 mg) and 2-cyanothioacetamide (0.93 mmol, 93 mg, 3.0 equiv.) in EtOH (1.5 mL), a few drops of piperidine were added. After being stirred at 80C for 2 h, EtOH was evaporated and crude product was redissolved in CH3CN. (0432) Butyl(chloromethyl)sulfane (0.62 mmol, 85.5 mg) and Et3N (0.93 mmol, 94.1 mg, 130 mu) were then added and the reaction mixture was stirred at 80C for 20 min. Once complete, the reaction was diluted with EtOAc and water. The organic phase was separated and aqueous layer was extracted twice with EtOAc. The combined extractions were washed with saturated NaCl solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography to give 99 mg of designed product (77%). H NMR (400 MHz, CDC13) delta 7.96 (d, / = 3.1 Hz, 1H), 7.85 (s, 1H), 7.56 (d, / = 3.1 Hz, 1H), 7.37 (s, 1H), 4.49 (s, 2H), 3.60 (s, 3H), 2.72 (t, / = 7.4 Hz, 2H), 2.48 (s, 3H), 1.62 (p, / = 7.3 Hz, 2H), 1.40 (h, / = 7.3 Hz, 2H), 0.90 (t, / = 7.3 Hz, 3H). ESI- MS (m/z): 416.6 [M+H]+.

The synthetic route of 7357-70-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CASE WESTERN RESERVE UNIVERSITY; MARKOWITZ, Sanford; GERSON, Stanton; DESAI, Amar; HO, Won Jin; (185 pag.)WO2016/144958; (2016); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 873697-68-8,Some common heterocyclic compound, 873697-68-8, name is 3-Amino-2-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.

To 3-amino-2- fluorobenzonitrile (0.5 g, 3.67 mmol) in DCM (10 mL) cooled to 0 C, was added pyridine (1 mL) and methyl chloroformate (0.313 mL, 4.04 mmol). After 24 h, the reaction was quenched with 0 (20 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with IN HC1 (20 mL), brine (20 mL) and dried (MgS04) to afford 0.7 g (98%) of 18A as brown solid. MS (ESI) m/z: 195.2 (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 3-Amino-2-fluorobenzonitrile, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; ORWAT, Michael J.; PINTO, Donald J.P.; SMITH II, Leon M.; SRIVASTAVA, Shefali; CORTE, James R.; WO2013/55984; (2013); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

154532-34-0, name is 3-(tert-Butyl)benzonitrile, 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. Product Details of 154532-34-0

A mixture of 0.84 g (5.1 mmol) 3-tert-butyl-benzonitrile, 1 mL (25% aq. NH3) and 0.1 g Raney-Nickel is hydrogenated at 40 C. After completion of reaction, the catalyst is filtered off and washed with MeOH. The solvent is removed in vacuo and the residue is purified by chromatography on silica gel (DCM/MeOH 90/10) to give 0.84 g of the desired product as a green oil.tR (HPLC, Nucleosil C18 column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, 100-20% CH3CN/H2O/0.5 min, flow: 1.0 ml/min): 2.81 min.Rf: (hexane/AcOEt=95/5): 0.26MS (ES+): 164=[M+H]+ 1H-NMR (400 MHz, CDCl3): 7.40-7.33 (m, 3H), 7.20-7.18 (m, 1H), 3.90 (s, 2H), 1.60 (bs, 2H), 1.39 (s, 9H).

The synthetic route of 154532-34-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Betschart, Claudia; Lerchner, Andreas; Machauer, Rainer; Rueger, Heinrich; Tintelnot-Blomley, Marina; Veenstra, Siem Jacob; US2008/132477; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 114897-91-5,Some common heterocyclic compound, 114897-91-5, name is 2-(4-Bromo-2-fluorophenyl)acetonitrile, molecular formula is C8H5BrFN, 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.

Step 1: 2- (4-BROMO-2-CHLORO-PHENYL)-2-METHYL-PROPIONITRILE (4-BROMO-2-FLUOROPHENYL) ACETONITRILE (1 g, 4.67 mmol) described in step 1 from Example A (97), benzyltriethylammonium chloride (0.02 g, 0.09 mmol) and 1,4-Dibromobutane (1.43 g, 0.79 mmol) were dissolved 50% aqueous NAOH (3 mL) and the resulting mixture was stirred for 3 hours at 50 C. Reaction was quenched with 4N HCI (50 mL extracted with EtOAc. The organic phase was dried over NA2SO4 and evaporated. The crude organic product was purified by flash column chromatography (5% EtOAc in hexanes) to give the product (1.25 g, 100%) as a clear OIL). H NMR (CDCI3) 5 : 1. 93-2. 17 (m, 4 H), 2.50-2. 55 (m, 2 H), 3.42-3. 46 (m, 2H), 7.26-7. 34 (m, 3 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(4-Bromo-2-fluorophenyl)acetonitrile, its application will become more common.

Reference:
Patent; PFIZER INC.; WO2004/74270; (2004); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 658-99-1, 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. 658-99-1, name is 2-(3,4-Difluorophenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Step A: Preparation of 2-(3,4-Difluorophenyl)-2- methylpropanenitrile; [0718] 2-(3,4-Difluorophenyl)acetonitrile (25.0 g, 163 mmol) and MeI(25.4 mL, 408 mmol) were dissolved in DMF (163 mL) and added dropwise to a suspension of sodium tert-butoxide (39.2 g, 408 mmol) in DMF at 0C. The resulting reaction mixture was stirred at 00C for 1 hour and then allowed to warm to ambient temperature for 1 hour. The reaction mixture was diluted with 400 mL of EtOAc, added to a separatory funnel, partitioned with water, washed 3 times with 200 mL of water, separated, dried over Na2SO4, and concentrated in vacuo to give the title compound (26.45 g) as a yellow oil.

The chemical industry reduces the impact on the environment during synthesis 2-(3,4-Difluorophenyl)acetonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AMGEN INC.; WO2008/76427; (2008); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 99066-80-5, 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. 99066-80-5 name is Methyl 3-cyano-5-nitrobenzoate, 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.

10%Pd/C (0.9 g) was added to the solution of methyl-3-cyano-5-nitrobenoate (25 mmol) in MeOH (200 mL) and THF (100 mL). Then the solution was stirred at room temperature for 4 hours. After filtration, it was concentrated to give methyl-3-amine-5-cyanobenoate in 95% yield.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-cyano-5-nitrobenzoate, and friends who are interested can also refer to it.

Reference:
Patent; Hutchison Medipharma Enterprises Limited; US2009/118292; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 151-18-8, name is 3-Aminopropanenitrile, A new synthetic method of this compound is introduced below., name: 3-Aminopropanenitrile

A solution of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid {3-(5-chloro-2-difluoromethoxy-phenyl)-1-[2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl]-1H-pyrazol-4-yl}-amide.dioxane (36 g, 57.0 mmol) in DCM (500 mL) was treated with 3-amino-propionitrile (5.0 mL, 68.4 mmol) and acetic acid (50 mL). The mixture was cooled in an ice bath before the addition of sodium triacetoxyborohydride (18.1 g, 85.4 mmol) portionwise. The reaction was allowed to warm to room temperature and stirred for 1.5 hours. The mixture was diluted with methanol and loaded onto a pad of Isolute SCX-2 which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. The basic fractions were combined and evaporated to afford pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (3-(5-chloro-2-difluoromethoxy-phenyl)-1-{2-[4-(2-cyano-ethylamino)-piperidin-1-yl]-2-oxo-ethyl}-1H-pyrazol-4-yl)-amide as a pale brown solid (31.1 g, 91%). LCMS (Method 3) [M+H]+=598.2, RT=2.25 min. 1H NMR (400 MHz, CDCl3) delta: (ppm) 9.84 (s, 1H), 8.78 (dd, 1H, J=1.6, 6.9 Hz), 8.69 (s, 1H), 8.58-8.55 (m, 1H), 8.40 (s, 1H), 7.68 (d, 1H, J=2.5 Hz), 7.41 (dd, 1H, J=2.7, 8.7 Hz), 7.28 (d, 1H, J=8.7 Hz), 7.28 (s, 1H), 7.00 (dd, 1H, J=4.2, 6.9 Hz), 6.50 (t, 1H, J=74.1 Hz), 5.08 (d, 1H, J=15.4 Hz), 5.02 (d, 1H, J=15.5 Hz), 4.37 (d, 1H, J=13.4 Hz), 3.88 (d, 1H, J=13.4 Hz), 3.22-3.12 (m, 1H), 3.02 (t, 1H, J=6.4 Hz), 2.98-2.86 (m, 2H), 2.82-2.72 (m, 1H), 2.52-2.46 (m, 2H), 1.96-1.83 (m, 2H), 1.36-1.20 (m, 2H).

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; Genentech, Inc.; Zak, Mark Edward; Ray, Nicholas Charles; Goodacre, Simon Charles; Mendonca, Rohan; Kellar, Terry; Cheng, Yun-Xing; Li, Wei; Yuen, Po-Wai; US2015/336962; (2015); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 874-97-5, 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. 874-97-5 name is 3-Cyanobenzyl alcohol, 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.

3-Cyanobenzyl alcohol (308 mg, 2.32 mmol), N-hydroxyphthalimide (416 mg, 2.55 mmol) and triphenylphosphine (668 mg, 2.55 mmol) were dissolved in THF (8 mL). Diethyl azodicarboxylate (DEAD) (0.40 mL, 2.55 mmol) was added dropwise while stirring to the solution and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was filtered and the residue washed with THF (4 mL) and dried under high vacuum. The crude product (1.24 g, 4.46 mmol) was dissolved in ethanol (8 mL) and hydrazine monohydrate (0.43 mL, 8.92 mmol) was added. The reaction was refluxed for 2 h and filtered. Ethanol was removed under reduced pressure and the residue suspended in ethyl ether. The ethyl ether layer was washed with 3% Na2CO3 (2*10 mL), brine (10 mL) and concentrated. The crude product (830 mg, 5.61 mmol) was dissolved in THF (15 mL) and cooled to 0 C. Lithium aluminum hydride (1 M in THF, 11.2 mL, 11.2 mmol) was added dropwise and the reaction was stirred overnight at room temperature. It was then quenched with methanol (10 mL) and water (2 mL). The mixture for stirred for a further 30 min. The salts were filtered off and the solvent removed by evaporation in vacuo. The crude product was purified by silica gel flash column chromatography using 20% MeOH/dichloromethane as eluent to afford the desired product as white solid (59 mg, 0.388 mmol, 17% over 3 steps). 1H NMR (CDCl3, 300 MHz): delta (ppm) 4.07 (s, 2H), 4.63 (s, 2H), 5.18 (s, 4H), 7.36-7.44 (m, 4H).

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

Reference:
Patent; NEWLINK GENETICS CORPORATION; Mautino, Mario; Jaipuri, Firoz; Marcinowicz-Flick, Agnieszka; Kesharwani, Tanay; Waldo, Jesse; (201 pag.)US10047066; (2018); B2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts