Month: March 2021

Application of 7357-70-2,Some common heterocyclic compound, 7357-70-2, name is 2-Cyanothioacetamide, molecular formula is C3H4N2S, 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.

Preparation 8 Synthesis of 2-cyano-3-oxo-thiobutyramide To a stirring solution of 2-cyano-thioacetamide, (1016 g, 9.84 mol) in pyridine (2.60 L), chilled to 0 C., add acetyl chloride over 2 hours (785 mL, 11.03 mol) keeping reaction temperature below 20 C. Warm to room temperature over 1 hour, add water (4 L) and stir until dissolution of all solids. Add an aqueous 12 M solution of hydrochloric acid (HCl, 250 mL) until acidic (pH=1) to give a red-brown precipitate. Stir for 1 hour at 0 C., filter, dry the collected solid under vacuum to give the title compound as an orange solid (926 g, 66%). A second crop can be harvested from the mother liquors by adding 12 M aqueous (500 mL) to give the title compound (353 g, 25%).

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

Reference:
Patent; Britton, Thomas Charles; Dehlinger, Veronique; Fivush, Adam Michael; Hollinshead, Sean Patrick; Vokits, Benjamin Paul; US2009/253750; (2009); A1;,
Nitrile – Wikipedia,
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These common heterocyclic compound, 40497-11-8, name is Ethyl 2,3-dicyanopropanoate, 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. Computed Properties of C7H8N2O2

Add 0.01 mol of 3-fluoroaniline and a small amount of ethanol to a 250 mL round bottom three-necked flask.Under ice bath, 3.0 mL (0.035 mol) of concentrated hydrochloric acid was added dropwise with stirring.Dissolve 0.018 mol of sodium nitrite in 10 mL of water.Slowly drip into the flask, and after the completion of the dropwise addition, the reaction was carried out for 0.5 h to obtain a yellow diazonium salt solution.Add 0.01 mol of ethyl 2,3-dicyanopropionate to a three-necked flask.The prepared diazonium salt solution was dropped into the flask, and the reaction was added dropwise for 2 hours.Ammonia water was added, the pH was adjusted to 9-10, and the reaction was carried out for 2 h at room temperature.After the reaction was completed, it was extracted with 40 mL of dichloromethane, and the organic layer was washed with water (2¡Á30 mL).Wash with saturated sodium chloride solution (1¡Á40 mL), dry over anhydrous magnesium sulfate.The solvent was crystallized under reduced pressure to give the product 1.18 g,yield: 58.3%,

The synthetic route of Ethyl 2,3-dicyanopropanoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nanjing Tech University; Wan Rong; Chen Fuli; Han Zhenyu; Fu Xiaohuan; Jiang Peng; (17 pag.)CN108203450; (2018); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 1187-42-4,Some common heterocyclic compound, 1187-42-4, name is Diaminomaleonitrile, molecular formula is C4H4N4, 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.

General procedure: AlCl3 (15 molpercent) was added to a solution of DAMN (1 mmol), ketone (1 mmol) and isocyanide (1 mmol), in 5 ml of CH3CN. The resulting mixture was stirred for an appropriate time at room temperature. After completion of the reaction, as indicated by thin-layer chromatography (TLC; ethyl acetate=n-hexane 3=1), the product was precipitated by addition of 10 ml of water. The precipitate was filtered off, washed with water, and then recrystallized from acetone. In the case of aromatic aldehyde, precipitate after filtration was loaded on column chromatography with 20percent ethyl acetate?hexane as an eluent system to furnish the product.

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

Reference:
Article; Bhosale, Shrikar M.; Naik, Nilesh H.; Kusurkar, Radhika S.; Synthetic Communications; vol. 43; 23; (2013); p. 3163 – 3169;,
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Electric Literature of 52133-67-2, 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. 52133-67-2, name is Ethyl 2-cyano-4,4-diethoxybutyrate belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

4-Hydroxybenzamidine hydrochloride (15.2 g) was dissolved in absolute ethanol (520 ml.) and a part of the ethanol (370 ml.) was subsequently distilled off again. More absolute ethanol (370 ml.) was added to this receiving solution, together with DBU (30 ml_), 2-cyano-4,4-diethoxy-butyric acid ethyl ester (40.0 g) and triethyl amine (26 ml_). The resulting mixture was heated until reflux and further refluxed for 45 hours (“hrs”). Most of the solvent (430 ml.) was then distilled off while the remainder was allowed to cool to 50 0C. An aqueous solution of hydrochloric acid (2.3 M, 229 ml.) was added dropwise, then the reaction mixture was allowed to cool to ambient temperature and stirring was continued for 1 hr. The resulting precipitate was filtered off, washed with water (3 x 100 ml.) and dried in vacuo at 40 0C to yield 16.0 g 2-(4-hydroxy-phenyl)-7/-/-pyrrolo[2,3-d]pyrimidin-4-ol

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, Ethyl 2-cyano-4,4-diethoxybutyrate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SOLVAY PHARMACEUTICALS GMBH; WO2009/153261; (2009); A1;,
Nitrile – Wikipedia,
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Electric Literature of 127946-77-4, These common heterocyclic compound, 127946-77-4, name is 1-Amino-1-cyclopropanecarbonitrile hydrochloride, 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.

Step 5To a solution of 3-(morpholin-4-sulfonyl)-2(i?)-[2,2,2-trifluoro-l(5}-(4-fluorophenyl)- EPO ethylamino] -propionic acid (0.034 g, 0.082 mmol) and the HCl salt of 1-aminocyclopropane- carbonitrile (OmegaChem, 0.013 g, 0.107 mmol) in DMF (1 mL) at rt was added solid HATU (PacificChem, 0.041 g, 0.107 mmol) in one portion followed by DIPEA (Aldrich, 0.043 mL, 0.246 mmol) to produce a bright yellow, clear solution. After stirring at rt for 1 h, the reaction was diluted in EtOAc and quenched with 10% aqueous NaHCO3. Water was added to dissolve precipitated solids. The aqueous layer was separated and extracted with EtOAc. The combined organics were washed with brine and dried over anhydrous Na2SO4. Following concentration in vacuo, the crude product was purified by column chromatography on SiO2 (2/1 EtOAc/Hex). Following concentration in vacuo, 0.020 g (51%) of N-(l-cyanocyclopropyl)-3-(morpholin-4- sulfonyl)-2(R)-[2,2,2-trifluoro- 1 (5)-(4-fluorophenyl)ethylamino]propionamide was obtained as?a white foamy solid with repeated concentration from CH2Cl2. LC/MS: 501.4 (M+Nua)+; 479.3 (M+H)+; 477.2 (M-H)”.

The synthetic route of 127946-77-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AXYS PHARMACEUTICALS, INC.; WO2006/60810; (2006); A1;,
Nitrile – Wikipedia,
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Electric Literature of 57381-37-0, 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. 57381-37-0 name is 2-Bromo-5-chlorobenzonitrile, 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.

Example 50 : (R)-4 ‘-( 4-Amino-8-methyl-5-oxo-7,8-dihvdropyrimido [5,4- f| [ 1 ,41 oxazepin-6( 5H)-yl)-4-chloro-2 ‘-fluor obiphenyl-2-carbonitrile; (i~)-4-Amino-6-(3-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)-8- methyl-7,8-dihydropyrimido[5,4-f][l ,4]oxazepin-5(6H)-one (Intermediate 51 ; 290 mg, 0.70 mmol), PdCl2(dppf)-DCM adduct (28.6 mg, 0.04 mmol), potassium phosphate (0.07 mL, 0.84 mmol) and 2-bromo-5-chlorobenzonitrile (182 mg, 0.84 mmol) were suspended in DME (3 mL), ethanol (1.5 mL) and water (0.75 mL) and sealed into a microwave tube, degassed under vacuum and the atmosphere replaced with nitrogen. The reaction was heated to 130 C for 90 minutes in the microwave reactor and cooled to RT. The reaction mixture was evaporated to dryness and redissolved in methyl THF (25 mL), and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried over Na2SC”4, filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep CI 8 OBD column, 5mu silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (74.0 mg, 24.94 %) as a white solid. 1H NMR (400 MHz, CDC13, 30C) 2.61 (3H, s), 3.89 – 4.00 (2H, m), 4.86 – 5.08 (1H, m), 5.51 – 5.74 (1H, m), 7.22 (1H, d), 7.49 (2H, dd), 7.66 (1H, dd), 7.78 (1H, d), 7.82 – 8.07 (1H, m), 8.33 (1H, s). m/z (ES+), (M+H)+ = 424

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

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BIRCH, Alan, Martin; GOLDBERG, Frederick, Woolf; LEACH, Andrew; WO2011/121350; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 90357-53-2, A common heterocyclic compound, 90357-53-2, name is N-(4-Cyano-3-(trifluoromethyl)phenyl)methacrylamide, molecular formula is C12H9F3N2O, 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 29; S-r¡ã-Fluoro-phenvO-S-methYl-S^-dihydro-SigmaH-pyrazole-S-carboxylic acidM-cvano-S-trifluoromethyl-PhenvD-amide and S-r¡ã-Fluoro-phenvO-S-methvM.S-dihvdro-SH-pyrazole-S-carboxylic acid r¡ã-cvano-S-trifluoromethyl-phenvQ-amide; Compound No.1 and Compound No.64; 2-[(1 E)-(4fluorophenyl)methylidene] toluenesulfonylhydrazone, prepared according to the procedure described in Example 29 (600 mg, 2.1 mmol) in THF (20 ml) was treated by NaH (60%, 120 mg, 3 mmol) at 0C for 20 min, followed by the addition of N-(4-cyano-3-trifluoromethyl-phenyl)-2-methyl- acrylamide (500 mg, 2.0 mmol). The reaction mixture was then heated to 55C overnight, then quenched by NaHCO3, and extracted by ethyl acetate. The organic layer was combined, washed with brine, dried over Na2SO4 and concentrated to yield crude product as a mixture. Purification of the crude product on a column yielded the title compound as separate products, as a white solids.5-(4-Fluorophihenyl)-3-methyl-3,4-dhydro-2H-pyrazole-3-carboxylic acid (4-cyano-3-trifluoromethyl-phenyl)-amide (Hexane: ethyl acetate, 2:1 , Rf= 0.45, 475 mg, 61 %)5-(4-Fluoro-phenyl)-3-methyl-4,5-dihydro-3H-pyrazole-3-carboxylic acid (4-cyano-3-trifluoromethyl-phenyl)-amide(Hexane: ethyl acetate: 2:1 , Rf=0.6, 100 mg, 13%): MS (m/z): MH+ (391) EPO 1H NMR (CDCI3) delta 8.50 (s, 1 H), 8.10 (s, 1 H), 7.90 (del, J=1.5 Hz, 0.2 Hz, 1 H), 7.75 (d, J=1.5 Hz, 1 H), 7.20 (m, 2H), 7.10 (m, 2H), 5.60 (t, J=0.9 Hz, 1 H), 3.00 (dd, J=1.0 Hz, 0.8 Hz, 1 H), 1.87 (s, 3H), 1.55 (t, J=1.1 Hz, 0.6 Hz, 1 H).

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; JANSSEN PHARMACEUTICA N.V.; WO2006/55184; (2006); A2;,
Nitrile – Wikipedia,
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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. 57381-49-4, name is 2-Bromo-4-chlorobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., category: nitriles-buliding-blocks

Step 1 4-chloro-2-(2,5-dimethoxypyridin-4-yl)benzonitrile 185b 2-Bromo-4-chloro-benzonitrile 185a (5.92 g, 27.33 mmol, prepared by a known method disclosed in “”) was dissolved in 180 mL 1,4-dioxane, then compound 1d (5 g, 27.33 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (2.03 g, 2.73 mmol) and potassium carbonate (11.33 g, 81.98 mmol) were added. Under an argon atmosphere, the reaction solution was warmed up to 110C, and stirred for 16 hours. The reaction solution was naturally cooled to room temperature, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column with elution system B to obtain the title compound 185b (6.5 g, yield: 86.59%).

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 57381-49-4.

Reference:
Patent; Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co., Ltd.; YANG, Fanglong; WANG, Weimin; LI, Xiaodong; CHEN, Gang; HE, Feng; TAO, Weikang; (198 pag.)EP3486242; (2019); A1;,
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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. 1000339-52-5, name is 3-Fluoro-2-nitrobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 1000339-52-5

Synthesis of 2-nitro-3-(phenylamino)benzonitrile Aniline (2.75 mL, 30.1 mmol) was added into THF (60 mL). Sodium hydride (0.867 g, 36.1 mmol) was added and stirred for 1 hour. 3-Fluoro-2-nitrobenzonitrile (5 g, 30.1 mmol) was added and stirred for about 16 hours at room temperature. Water (2 mL) was added to quench the unreacted sodium hydride. The solvent was then evaporated and the residue was then purified by column chromatography using THF:hexane (1:4, v/v) as the eluent. 6.0 g (83% yield) of a red solid was obtained.

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 1000339-52-5.

Reference:
Patent; Universal Display Corporation; KWONG, Raymond; LAM, Sze Kui; LAM, Siu Tung; TSANG, Kit Yee; LEE, Chi Hang; SZIGETHY, Geza; (159 pag.)US2016/218303; (2016); A1;,
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Application of 19924-43-7, 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. 19924-43-7, name is 2-(3-Methoxyphenyl)acetonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To a stirring suspension of KOtBu (2.0 mmol) in 1,4-dioxane (5 mL) at 0C, corresponding (het)arylacetonitrile (1a-f, 10a-c) (1.0 mmol) in 1,4-dioxane (2 mL) was added dropwise. After further stirring for 10 minutes, a solution of respective Dithioester (2a-i) (1.0 mmol) in 1,4-dioxane (2 mL) was added to the reaction mixture at 0C, followed by further stirring for 1 h at ambient temperature (monitored by TLC). Iodine (506 mg, 2.0 mmol) was added and the reaction mixture was heated at 90C with continuous stirring (monitored by TLC). It was then diluted with 10% aq. Na2S2O3 solution (50 mL) and extracted with EtOAc (3×25 mL), and the combined organic layer was washed with water (3×25 mL) and brine (1×25 mL), dried (anhyd. Na2SO4), and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography using EtOAc/hexane as eluent.

The synthetic route of 2-(3-Methoxyphenyl)acetonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Article; Bonagiri, Saraiah; Acharya, Anand; Pasha, Mohamed A.; Hiriyakkanavar, Ila; Tetrahedron Letters; vol. 58; 49; (2017); p. 4577 – 4582;,
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