Month: July 2021

623-00-7, name is 4-Bromobenzonitrile, 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. Application In Synthesis of 4-Bromobenzonitrile

Example 1 4-Bromo-3-nitrobenzonitrile To a solution of 4-bromobenzonitrile (4.0 g, 22 mmol) in conc. H2SO4 (10 mL) was added dropwise at 0 C. nitric acid (6 mL). The reaction mixture was stirred at 0 C. for 30 min, and then at room temperature for 2.5 h. The resulting solution was poured into ice-water. The white precipitate was collected via filtration and washed with water until the washings were neutral. The solid was recrystallized from an ethanol/water mixture (1:1, 20 mL) twice to afford 4-bromo-3-nitrobenzonitrile as a white crystalline solid (2.8 g, 56%). 1H NMR (300 MHz, DMSO-d6) delta 8.54 (s, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.99 (d, J=8.4 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) delta 150.4, 137.4, 136.6, 129.6, 119.6, 117.0, 112.6; HPLC ret. time 1.96 min, 10-100% CH3CN, 5 min gradient; ESI-MS 227.1 m/z (MH+).

The synthetic route of 623-00-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Vertex Pharmaceuticals Incorported; US2011/98311; (2011); A1;,
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Synthetic Route of 159847-81-1, 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. 159847-81-1, name is Methyl 2-amino-5-cyanobenzoate belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Methyl 2,4-dichloro-6-cyanoquinoline-3-carboxylate, 13 [00167] To a solution of methyl 2-amino-5-cyanobenzoate (5.68 mmol) in DCM (lOmL) was added triethyamine (8.52 mmol) followed by methyl 3-chloro-3-oxopropionate (7.38 mmol). The resulting reaction mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between EtOAc and 1M HCl and the layers then separated. The organic layer washed sequentially with saturated aqueous NaHC03 followed by brine. The organic layer was dried over Na2S04, filtered, and concentrated in vacuo. The resulting residue was carried on without further purification. [00168] The residue from above was treated with 0.5M NaOMe in MeOH (6.83 mmol). The heterogenous mixture was stirred at ambient temperature for 30 min. Diethyl ether was then added to the reaction mixture and the solid was collected via vacuum filtration, washing with ether. The obtained solid was carried on without further purification. [00169] To a flask containing the solid from above cooled to 0 C was added POCI3 (15 mL). The mixture became warm and bubbled. The resulting reaction mixture was heated to 90C for 3 h. Cooled the dark reaction mixture to ambient temperature and poured it very slowly into stirring saturated aqueous NaHC03 cooled to 0 C. Solid NaHC03 was then added until the solution was basic. The aqueous solution was extracted with EtOAc (3x). The combined organic layers were dried over Na2S04, filtered, and concentrated in vacuo. The obtained residue was purified via flash column chromatography, eluting with 9: l/hexanes:EtOAc, to yield the intermediate 13 (29% over 3 steps). M S ESI (tn/z) 281 Cvl Pi } . FontWeight=”Bold” FontSize=”10″ B NMR (300 MHz, CDCK) delta 8.63 (d, I B, J l .K Hz), 8.16 (d, 1H, J=8.4 Hz), 8.00 (dd, 1H, J=L8, J2=SA Hz), 4.08 (s, 3H); 13C NMR (CDCI3, 75MHz) 6 163.4, 148.9, 148.1 , 141 .8, 133.3, 1 30.8, 130.6, 128.8, 124.3, 1 1 7.7, 1 12.8, 54.1 .

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

Reference:
Patent; THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK; LANDRY, Donald, W.; DENG, Shixian; FIORITO, Jole; ARANCIO, Ottavio; WASMUTH, Andrew; WO2015/9930; (2015); A2;,
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1897-41-2, name is 2,3,5,6-Tetrachloroterephthalonitrile, 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. name: 2,3,5,6-Tetrachloroterephthalonitrile

Comparative Example 3 Preparation of 2,3,5,6-tetrachloro-1,4-benzenedicarboxylic acid (compound 2) from 2,3,5,6-tetrachloro-1,4-benzenedicarbonitrile (compound 3) 5.32 g (0.02 mol) of 2,3,5,6-tetrachloro-1,4-benzenedicarbonitrile and 17.65 g of 90.0percent sulfuric acid were charged into a reactor, and a hydrolysis of 2,3,5,6-tetrachloro-1,4-benzenedicarbonitrile was performed under atmospheric pressure. The temperature and reaction time were as specified in Table 1. After the completion of the reaction, the same processing as in Example 1 was conducted. As a result, 2,3,5,6-tetrachloro-1,4-benzenedicarboxylic acid was obtained. Yield: 5.9 g (isolation yield 97percent), and IR (KBr):

The synthetic route of 1897-41-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SDS Biotech K.K.; US2001/25121; (2001); A1;,
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Application of 453565-55-4, The chemical industry reduces the impact on the environment during synthesis 453565-55-4, name is 5-Fluoroisophthalonitrile, I believe this compound will play a more active role in future production and life.

3.00 g (9.03 mmol) of 3,3′-9H-biscarbazole and 4.98 g (36.0 mmol) of potassium carbonate were placed in a 200 ml three-necked flask, and the flask was purged with nitrogen. N, N-Dimethylformamide (78.0 ml) was added to the mixture, and the mixture was stirred at room temperature for 2 hours under a nitrogen stream. After adding 2.93 g (18.0 mmol) of 5-fluoroisophthalonitrile into this mixture, the mixture was stirred at 70 C for 20 hours under a nitrogen atmosphere. After the stirring, the solvent in the mixture was removed by distillation under reduced pressure. After removal, 100 ml of chloroform and 50 ml of water were added to this mixture and stirred. After stirring, the mixture was subjected to suction filtration to obtain a filtrate. The obtained aqueous layer of the filtrate and the organic layer were separated, and the organic layer was washed with water. After washing, magnesium sulfate was added to the organic layer and dried. After drying, the mixture was subjected to suction filtration to obtain a filtrate. The obtained filtrate was concentrated and purified by silica gel column chromatography. As the developing solvent, a mixed solvent of chloroform: ethyl acetate = 10: 1 was used first. The resulting fraction was concentrated, and the resulting solid was recrystallized from a mixed solvent of chloroform and methanol to obtain 0.700 g of a pale orange powdery solid as a target product in a yield of 13.3%.

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

Reference:
Patent; KokuritsuDaigakuHojinKyushuDaigaku; Nippon Steel & Sumikin Kagaku Corporation; Li, Bo; Orita, Akihiro; Miyazaki, Hiroshi; Ohterra, Junjo; Nomura, Hiroko; Adachi, Jihaya; (38 pag.)KR2016/34335; (2016); A;,
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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. 4426-11-3, name is Cyclobutanecarbonitrile, A new synthetic method of this compound is introduced below., name: Cyclobutanecarbonitrile

l-[5-(trifluoromethyl)pyridin-2-yl]cyclobutanecarbonitrile[187] 2-Fluoro-5-(trifluoromethyl)pyridine (0.603 mL, 5 mmol) and cyclobutane- carbonitrile (0.514 mL, 5.50 mmol) were dissolved in toluene (20 mL). 1M NaHMDS (5.50 mL, 5.50 mmol) in THF was added, and the reaction stirred at ambient temperature for 3 days. The reaction mixture was quenched with water and extracted three times with diethyl ether. The combined organic layers were washed with brine, dried with MgS04, filtered, and concentrated. The residue was chromatographed on an AnaLogix SF25-60 g column and eluted with 5% EtOAc in hexanes to give Example 115A (0.36 g, 1.592 mmol, 31.8% yield). MS (DCI+): m/z 244.0 (M+NH4). XH NMR (300 MHz, DMSO-d6) ? 9.09 – 9.02 (m, 1H), 8.33 (dd, J= 8.3, 2.2 Hz, 1H), 7.85 (d, J= 8.3 Hz, 1H), 2.89 – 2.69 (m, 4H), 2.39 – 2.21 (m, 1H), 2.16 – 2.00 (m, 1H).

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

Reference:
Patent; ABBVIE INC.; BAYBURT, Erol K.; CLAPHAM, Bruce; COX, Phil B.; DAANEN, Jerome F.; GOMTSYAN, Arthur; KORT, Michael E.; KYM, Philip R.; VOIGHT, Eric A.; SCHMIDT, Robert G.; DART, Michael J.; GFESSER, Gregory; WO2013/62966; (2013); A2;,
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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 185836-35-5 as follows. Recommanded Product: 4-(Benzyloxy)-2-fluorobenzonitrile

Step 2: Production of 4-benzyloxy-2-fluoro-N-hydroxybenzamidine To a suspension of 4-benzyloxy-2-fluorobenzonitrile (15.0 g, 66 mmol) in water (150 ml) and ethanol (150 ml) were added hydroxylamine hydrochloride (6.42 g, 92.4 mmol) and sodium carbonate (10.5 g, 99.0 mmol), and the mixture was heated under reflux for 18 hr. The reaction mixture was appropriately evaporated under reduced pressure and the residue was extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the obtained solid was washed with a mixed solvent of n-hexane:ethyl acetate=1:1 to give 4-benzyloxy-2-fluoro-N-hydroxybenzamidine (14.7 g, yield 86%). 1H-NMR(400MHz, deltappm, DMSO-d6): 9.51(1H, s), 7.31-7.45 (6H, m), 6.92(1H, dd, J=12.8, 2.0Hz), 6.85(1H, dd, J=8.8, 2.8Hz), 5.71(2H, s), 5.14(2H, s).

According to the analysis of related databases, 185836-35-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Japan Tobacco Inc.; EP1688420; (2006); A1;,
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Electric Literature of 213598-11-9, 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 213598-11-9 as follows.

To a solution of methyl 3-cyano-4-hydroxybenzoate (82 g, 463 mmol; J. Med. Chem, 2002,45, 5769) in dimethylfonnamide (800 mL) was added 2-iodopropane (93 mL, 926 mmol) and potassium carbonate (190 g, 1.4 mol). The resulting mixture was heated at 50 C for 16 h, at which time it was allowed to cool to room temperature. The reaction was filtered and the mother liquor diluted with 0.5 N sodium hydroxide (1 L). The resulting mixture was extracted with ether (2 x I L) and the organics washed with 1 N HCI (1 L) and brine (700 mL), dried (MgSO4) and concentrated to give 100 g (-100%) of methyl 3-cyano-4- [(1-methylethyl) oxy]benzoate as a yellow solid. 3-Cyano-4-[(1-methylethyl)oxy]benzoic acid: [00392] To a cooled (0 C) solution of methyl 3-cyano-4-[(1-methylethyl)oxyJbenzoate (100 g, 463 mmol) in tetrahydrofuran (500 mL) was added 10% potassium hydroxide (500 mL). The resulting solution was allowed to warm to room temperature and maintained for 16 h, at which time it was concentrated to remove the tetrahydrofuran. The residue was diluted with water (500 mL) and washed with ether (2 x 500 mL). The aqueous layer was then acidified with 3 N HCI and stood for 2 h. The solids were collected by filtration and washed several times with water, then dissolved in methylene chloride (1 L). The mostly homogeneous mixture was filtered through Celite and concentrated to a minimal volume of methylene chloride. Collection ofthe solids by filtration gave 82 g (87%) of 3-cyano-4-[(1- methylethyl)oxy]benzoic acid as a white solid. Scheme B: Reagents and Conditions: a) 4N HCI/dioxane, rt; b) HBTU, i-Pr2NEt, DMF, rt; c) 1- ethoxyvinyltn-n-butyltin, PdCh(PPh3)2, dioxane, 100 C; d) NBS, THF/HzO (3:1), rt; e) 2- amino-3-picoline, NaHC03, i-PrOH, 80 C . (3tS)-3-Amino-4-(4-bromophenyl)-1 -butane. hydrochloride. [00393] 1,1-Dimethylethyl {(I S)-l-[( 4-bromophenyl)methyl]-3- hydroxypropyl}carbamate (4.4 g, 12.8 mmol) was dissolved in 4N HCl/dioxane (20 mL). After 2 h, the reaction mixture was concentrated in vacuo to give 3.69 g (94%) of the title compound as a white solid. LC/MS (ES) m/e 244.0 (M + H)+. N- {( 1 S)- I -[ (4-Bromophenyl)methyl]-3-hydroxypropyl }-3-cyano-4-[(1- methylethyl)oxy]benzamide. [00394] To a suspension of (3S)-3-Amino-4-(4-bromophenyl)-1-butanol hydrochloride (1.80 g, 6.42 mmol) in dry DMF (32 mL) was added N, N-diisopropylethyl amine (2.49 g, 19.3 mmol) and the resultant clear solution was stirred for 3 min. 3-Cyano-4-[(1- methylethyl) oxy]benzoic acid (1.45 g, 7.06 mmol) and HBTU (2.68 g, 7.06 mmol) were added and the reaction was stirred at rt under nitrogen. After 1.5 h, the reaction mixture was quenched with water (50 mL) and extracted with EtOAc (3 X 30 mL). The extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (75% EtOAc/hexanes) to give 2.18 g (78%) of the title compound as a white solid. LC/MS (ES) m/e 431.2 (M + H)+. N-«(1S)-I- {[ 4-(Bromoacetyl)phenyl]methyl }-3-hydroxypropyl)-3-cyano-4-[(1- methylethyl) oxy]benzamide. [00395] A flask, dried with a heat gun under argon purge, was charged with N-{(1S)-1- [(4-bromophenyl)methyl]-3-hydrox5propyl}-3-cyano-4-[(1-methylethyl)oxy]benzamide (1.0 g, 2.32 mol). dichlorobis(triphenylphosphine)-palladium(II) (81 mg, 0.116 mol), tributyl(1- ethoxyvinyl) tin (1.68 g, 4.64 mmol), and 1,4-dioxane (15 mL). The mixture was stirred at 100 C for 2 hours under argon. Upon completion, as monitored by LCMS, the reaction was concentrated under reduced pressure and the residue was purified immediately on deactivated silica gel (65% EtOAc/hexanes with 5% triethylamine) to give 720 mg (1.70 mmol) of enol ether intennediate as a colorless foam which was immediately dissolved in THF:H20 (3: 1, 18 mL) and treated with N-bromosuccinimide (3 IS mg, 1.79 mmol). After 15 min at rt, the reaction mixture was concentrated under reduced pressure and the crude residue was diluted with EtOAc (30 mL), washed with biine (10 mL) and water (10 mL) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (80% EtOAc/hexanes) to give 651 mg (59%) of N-«(lS)-I- {[ 4-(bromoacetyJ)phenyl)methyl}-3- hydroxypropyl)-3-cyano-4-[(l -methylethyl)oxy]benzamide as a white tacky solid. LC/MS (ES) m/e 473.2 (M + H)+. 3-Cyano-N ((1S'(at)-3-hydroxy-1-{[(at)4-(8-methylimidazo[1,2-a]p(at)a-idin-2- yl)phenyl ] methj/I ) propyl)-4-[ ( 1 -methyl ethyl)oxy]benzamide. [00396] To a solution of N-( (1 S)-l- {[ 4-(bromoacetyl)phenyl]methyl }-3- hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (300 mg, 0.634 mmol) in i-PrOH (6 mL) was added 2-amino-3-picoline (Aldrich, 69 mg, 0.634 mmol) followed by solid NaHCO3 (64 mg, 0.761 mmol). The resultant suspension was heated to 80 C. After 7 h, a majority of the i-PrOH was removed under reduced pressure and the residue was dissolved in 3% MeOH/EtOAc (30 mL) and washed with water (10 mL) and brine (10 mL). The combined aqueous layers were extracted with 3% MeO…

According to the analysis of related databases, 213598-11-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CYTOKINETICS, INC.; SMITHKLINE BEECHAM CORPORATION; WO2005/107762; (2005); A2;,
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Adding a certain compound to certain chemical reactions, such as: 19472-74-3, name is 2-Bromophenylacetonitrile, 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 19472-74-3, Application In Synthesis of 2-Bromophenylacetonitrile

Step 1. Paraformaldehyde (2.17 ml, 14.8 mmol) and K2CO3 (1.37 g, 9.9 mmol) are added to a solution of commercially available 2-bromophenylacetonitrile (1.32 mL, 9.9 mmol) in DMF (60 mL). The reaction is stirred at 80C for 1 night. After cooling to r.t., water (100 mL) is added and the aqueous layer is extracted with EtOAc (150 mL, 50 mL). The combined organic extracts are washed with brine, dried over MgSC>4, filtered and evaporated. The crude compound is purified by prep. HPLC (Prep-HPLC-3 conditions) to give 2-(2- bromophenyl)acrylonitrile ( 561 mg, 27% yield) as an orange oil. 1H NMR (400 MHz, DMSO) <5: 7.77-7.74 (m, 1 H), 7.53-7.48 (m, 2 H), 7.42 (ddd, J1 = 2.9 Hz, J2 = 6.3 Hz, J3 = 8.0 Hz, 1 H), 6.61 (s, 1 H), 6.36 (s, 1 H). 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; IDORSIA PHARMACEUTICALS LTD; BOLLI, Martin; BROTSCHI, Christine; LESCOP, Cyrille; WILLIAMS, Jodi T.; (0 pag.)WO2019/234115; (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. 19924-43-7, name is 2-(3-Methoxyphenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C9H9NO

In a 10 mL single-neck round bottom flask under argon protection,A suspension of sodium dispersion in toluene (28.7% by weight, 5.00 mmol) was added followed by anhydrous tetrahydrofuran (1.0 mL),Dibenzo-18-crown-6 (5.00 mmol) was added at 0 C and stirred vigorously for 5 min. A solution of 1e (73.6 mg, 0.5 mmol) in anhydrous tetrahydrofuran (2.0 mL) was added, and the mixture was stirred vigorously at 0 C for 20 minutes. Then n-PrOH (5.00 mmol) was added. The reaction mixture was stirred vigorously at 0 C for 1 hour, and the reaction was quenched with a saturated aqueous sodium bicarbonate solution (2.0 mL). Anhydrous ether was added and the mixture was extracted with saturated sodium chloride solution. The organic phase was dried, concentrated, and separated by column chromatography to obtain 47.7 mg of the target compound 2e in a yield of 78%.

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 19924-43-7.

Reference:
Patent; China Agricultural University; An Jie; Luo Shihui; Ding Yuxuan; (13 pag.)CN110734414; (2020); A;,
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Synthetic Route of 13531-48-1, These common heterocyclic compound, 13531-48-1, name is Methyl 3-cyanobenzoate, 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.

To a solution of 3-Cyanobenzoic acid methyl ester (5Og, 310 mmol) in ethanol(500 mL) was added 50% aqueous hydroxylamine (41 mL, 620 mmol) at room temperature. The reaction mixture was stirred for 1 h at 100 0C and the solvents were removed under reduced pressure. The oily residue was dissolved in 20/80 ethanol/toluene (50 mL x 2) and then concentrated again. The desired ester (6 Ig, quan. yield) was obtained as a white powder with 98% purity (LC/UV). 1H-NMR (CDCl3) delta 9.76 (IH), 8.24 (IH), 7.82 (2H), 7.51 (IH), 5.92 (2H), 3.82 (3H).

The synthetic route of 13531-48-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PTC THERAPEUTICS, INC.; WO2008/45566; (2008); A1;,
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