Month: August 2021

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. 20925-27-3, name is 4-Amino-2-chlorobenzonitrile, A new synthetic method of this compound is introduced below., Computed Properties of C7H5ClN2

EXAMPLE 54A 2-chloro-4-iodobenzonitrile A solution of 4-amino-2-chlorobenzonitrile (30.5 g, 0.2 mol) in 1:1 diethyl ether/3M HCl (600 mL) at 0 C. was treated dropwise over 15 minutes with a solution of sodium nitrite (18 g, 0.26 mol) in water (100 mL), stirred 15 minutes, then treated with a solution of potassium iodide (50 g, 0.3 mol) in water (50 mL) dropwise over 45 minutes, warmed to room temperature, and stirred for 1.5 hours. The organic phase was washed with water (3*100 mL) and the combined aqueous layers were extracted with diethyl ether. The combined organic layers were combined, washed sequentially with saturated NaHCO3, 25% Na2S2O3, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 19:1/hexanes:ethyl acetate, triturated in hexanes, filtered, and dried to provide the desired product.

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; Claiborne, Akiyo K.; Gwaltney, II, Stephen L.; Hasvold, Lisa A.; Li, Qun; Li, Tongmei; Lin, Nan-Horng; Mantei, Robert A.; Rockway, Todd W.; Sham, Hing L.; Sullivan, Gerard M.; Tong, Yunsong; Wang, Gary; Wang, Le; Wang, Xilu; Wang, Wei-Bo; US2002/115640; (2002); A1;; ; Patent; Claiborne, Akiyo K.; Gwaltney II, Stephen L.; Hasvold, Lisa A.; Li, Qun; Li, Tongmei; Lin, Nan-Horng; Mantei, Robert A.; Rockway, Todd W.; Sham, Hing L.; Sullivan, Gerard M.; Tong, Yunsong; Wang, Gary; Wang, Le; Wang, Xilu; Wang, Wei-Bo; US2003/87940; (2003); A1;,
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Electric Literature of 55984-93-5, A common heterocyclic compound, 55984-93-5, name is 2-Methylterephthalonitrile, molecular formula is C9H6N2, 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.

Into a 250-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-methylbenzene-l,4-dicarbonitrile (4 g, 28.14 mmol, 1.00 equiv), [(tert-butoxy)(dimethylamino)methyl]dimethylamine (9.8 g, 56.23 mmol, 2.00 equiv) in N,N-dimethylformamide (50 mL). The resulting solution was stirred overnight at 75 °C, and then concentrated under vacuum. The resulting mixture was washed with 50 mL of hexane. The solids were collected by filtration. This provided 5.3 g (95percent) of 2-[(E)-2- (dimethylamino)ethenyl]benzene-l,4-dicarbonitrile as a yellow solid.

The synthetic route of 55984-93-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLOBAL BLOOD THERAPEUTICS, INC.; LI, Zhe; YU, Chul; YEE, Calvin W.; XU, Qing; GWALTNEY, II, Stephen L.; METCALF, Brian W.; LARDY, Matthew A.; RICHARDS, Steven; WO2015/171526; (2015); A2;,
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Synthetic Route of 14447-18-8, A common heterocyclic compound, 14447-18-8, name is Benzyl cyanoacetate, molecular formula is C10H9NO2, 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.

2-Cyano-4,4, 8-trimethyl-non-2-enoic acid benzyl ester. To a mixture of 2,2, 6-Trimethyl-heptanal (1.05 g, 6.73 mmol), piperidine (0.19 mL, 2.01 mmol) and benzyl cyanoacetate (1.29 g, 7.4 MMOL) in toluene (50 mL) was added glacial acetic acid (0.72 g, 12.1 mmol). The flask was fitted with a Dean-Stark trap, and the mixture was heated at reflux for 18. The mixture was cooled, treated with dilute HCI, and the layers were separated. The organics were washed with a saturated sodium bicarbonate solution followed by brine, and dried (MGS04), filtered and concentrated. The residual oil was purified by silica gel chromatography (98/2 hexane/EtOAc) to give 1.3 g of 2-Cyano-4, 4, 8-TRIMETHYL-NON-2-ENOIC acid benzyl ester M/Z 314 (M+).

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; WARNER-LAMBERT COMPANY LLC; WO2005/30184; (2005); A2;,
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Electric Literature of 98730-77-9, 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. 98730-77-9 name is 1-(Hydroxymethyl)cyclopropanecarbonitrile, 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.

1 -(Hydroxymethyl)cyclopropanecarbonitrile (1 .1 g, 1 1 .3 mmol), TBDPSCI (2.66 mL, 1 1 .3 mmol, 1 eq.), imidazole (926 mg, 13.6 mmol, 1 .2 eq.) and DMAP (69 mg, 0.57 mmol, 0.05 eq.) were combined in DCM (15 mL) and stirred at r.t. for 18 h. The mixture was partitioned between EtOAc (2 chi 20 mL) and water (20 mL), washed with brine, dried (MgS04) and solvent removed in vacuo. The residue was purified by MPLC on silica with gradient elution from 2-40% EtOAc/petrol to give the title compound as a clear oil (2.05 g, 54%); HRMS calc for CziHa NzSi 353.2044, found 353.2034.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(Hydroxymethyl)cyclopropanecarbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; CANCER RESEARCH TECHNOLOGY LIMITED; CHESSARI, Gianni; HOWARD, Steven; BUCK, Ildiko Maria; CONS, Benjamin David; JOHNSON, Christopher Norbert; HOLVEY, Rhian Sara; REES, David Charles; ST. DENIS, Jeffrey David; TAMANINI, Emiliano; GOLDING, Bernard Thomas; HARDCASTLE, Ian Robert; CANO, Celine Florence; MILLER, Duncan Charles; CULLY, Sarah; NOBLE, Martin Edward Maentylae; OSBORNE, James Daniel; PEACH, Joanne; LEWIS, Arwel; HIRST, Kim Louise; WHITTAKER, Benjamin Paul; WATSON, David Wyn; MITCHELL, Dale Robert; (293 pag.)WO2017/55860; (2017); 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. 6629-04-5, name is N-Cyanoacetylurethane, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: N-Cyanoacetylurethane

A suspension of 5-dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenylamine (24) (134 mg, 0.42 mmol) in water (5.6 mL) was treated with concentrated hydrochloric acid (2.8 mL). The reaction mixture was cooled to 00C and then was treated with a solution of sodium nitrate (36.5 mg, 0.529 mmol) in water (0.2 mL) under the surface of the reaction mixture followed by a water (0.2 mL) rinse. The reaction mixture was stirred at 00C for 30 min, and a solution formed. In a separate flask, equipped with a magnetic stirrer, was added N-cyanoacetylurethane (73 mg, 0.46 mol), water (9.4 mL) and pyridine (2.8 mL). This reaction mixture was cooled to 00C and the solution from the first reaction was quickly filtered and poured into the second reaction mixture. An orange precipitate formed and the suspension was stirred at 00C for 30 min. The solid was filtered and rinsed with water followed by petroleum ether. The solid was dried in a vacuum oven overnight at 800C to afford 2-cyano-2-{ [3,5-dichloro-4-(5-isopropyl-6-oxo-l,6-dihydro-pyridazin-3-yloxy)- phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester (30) (156 mg, 76%) as an orange solid; EI(+)-HRMS m/z calcd for Ci9Hi8Cl2N6O5 (M+H) 481.0789, found 481.0790. Molecular Weight =481.2985; Exact Mass =480.0716

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 6629-04-5.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2007/9913; (2007); 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. 1009-35-4, name is 4-Fluoro-3-nitrobenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 1009-35-4

Step A3-amino-4-fluorobenzonitrileUsing 4-fluoro-3-nitrobenzonitrile (13.64 g, 82.11 mmol) and according to the method of Reference Example 68, step A, the title compound (10.16 g, yield 91percent) was obtained as a pale-yellow solid.1H-NMR (300 MHz, CDCl3); delta(ppm) 3.94 (brs, 2H), 7.00-7.09 (m, 3H).

According to the analysis of related databases, 1009-35-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MITSUBISHI TANABE PHARMA CORPORATION; US2012/196824; (2012); A1;,
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Electric Literature of 19472-74-3, 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. 19472-74-3, name is 2-Bromophenylacetonitrile, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: A flask was equipped with a magnetic stir bar and charged with 1Hpyrrole-2-carbaldehyde (2a; 19.0 mg, 0.2 mmol, 1.0 equiv), 2-bromophenylacetonitrile(1a; 39.2 mg, 0.2 mmol, 1.0 equiv), and K3PO4(63.6 mg, 0.3 mmol, 1.5 equiv). The flask was evacuated and filledwith N2, and then anhydrous DMSO (2.0 mL) was introduced via a syringe.The flask was heated in a 130 C oil bath for 24 h, at which timeTLC analysis [petroleum ether (bp 60-90 C)-EtOAc, 10:1] indicatedcomplete consumption of 2a and 1a. The reaction mixture was cooledto r.t. and added to a sat. solution of NaCl (20 mL) and extracted withEtOAc (3 × 10 mL). The combined organic layers were dried (Na2SO4)and filtered. The filtrate was concentrated, and the residue was purified by column chromatography on SiO2 [petroleum ether (bp 60-90C)-EtOAc, 10:1 to 30:1] to give 3aa; yield: 32.9 mg (86%); tan yellowsolid; mp 155.6-156.3 C.

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

Reference:
Article; Jiang, Zeng-Qiang; Miao, Da-Zhuang; Tong, Yao; Pan, Qiang; Li, Xiao-Tong; Hu, Ren-He; Han, Shi-Qing; Synthesis; vol. 47; 13; (2015); p. 1913 – 1921;,
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Reference of 10406-25-4, The chemical industry reduces the impact on the environment during synthesis 10406-25-4, name is 4-(Aminomethyl)benzonitrile, I believe this compound will play a more active role in future production and life.

Precipitated crystals were collected through filtration, washed with water, and dried, to thereby obtain 11.9 g of p-cyanobenzoic acid (yield 90%, based on p-cyanobenzylamine). The p-cyanobenzoic acid obtained had a purity of 96%.

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-(Aminomethyl)benzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Showa Denko Kabushiki Kaisha; US6433211; (2002); B1;,
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Some common heterocyclic compound, 143879-80-5, name is 2,3,4-Trifluorobenzonitrile, molecular formula is C7H2F3N, 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. name: 2,3,4-Trifluorobenzonitrile

Scheme 21[0368] To 2,3,4-trifluorobenzonitrile (265 mg, 1.68 mmol) in a flask, a solution of D- leucine amide hydrochloride (282 mg, 1.68 mmol) and DIEA (0.880 mL, 5.06 mmol) in DMSO (5 mL) was added. After being stirred at room temperature for 68 h, water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2S04, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 0-70% EtOAc in hexane to give (R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamide (113 mg).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 143879-80-5, its application will become more common.

Reference:
Patent; PORTOLA PHARMACEUTICALS, INC.; JIA, Zhaozhong, J.; SONG, Yonghong; XU, Qing; KANE, Brian; BAUER, Shawn, M.; PANDEY, Anjali; WO2012/61418; (2012); A2;,
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Synthetic Route of 103146-25-4, These common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, 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.

10.0g of 4-(4-fluoro-benzoyl)-3-hydroxymethyl-benzonitrile (MW: 255.25, assay: 96.7%; 37.9mmol) are dissolved in 14OmL of toluene. 7.77g of (S)-2-lambda/,lambda/-dimethylaminophenylethanol (MW: 165.24, 47.0mmol, 1.24 eq.) and 2.51g of methylboronic acid (MW: 59.86, assay: 98%, 41.1mmol, 1.08eq.) are added. The solution becomes slightly turbid and drops of water are rapidly formed. The mixture is heated to 500C. At reduced pressure (~60-70mbar) -10OmL of toluene / water are carefully removed. 10OmL of toluene are added and -10OmL of toluene / water are removed. 12OmL of toluene are added and about -2OmL of toluene / water are removed to get a solution of mixed boronate (~80mmol) in about 25OmL of solvent. The water content is below 0.1% as determined by a Karl Fischer titration. The reaction is cooled to – 65C. Within about 10-20 minutes 38.OmL of a -2M solution of dimethylaminopropyl magnesiumchloride in THF (-2 eq.) are added. Thereby, the temperature does not exceed -500C. The solution is stirred for another 30 minutes. Reaction control is performed with HPLC (ee = 90%). After complete conversion (area% 4-(4-fluoro-benzoyl)-3-hydroxymethyl-benzonitrile <2%) the reaction is worked up.2OmL of water are and 35mL of 2M aqueous H2SO4 (70mmol) are added to get a pH of -1.5 in the aqueous layer. After phase separation, the organic layer is washed once with 2OmL water, adjusted to pH 1 with 2M aqueous H2SO4. 15OmL of CH2CI2 are added to the combined aqueous layers. 7M aqueous NH3 is now added (29mL) until a pH of -9.0 is reached. After phase separation the aqueous layer is washed twice with 25mL of MED (at pH 9.0). The combined CH2CI2 layers are washed with 15mL of water. 7OmL of H2O are added. 10.7mL of 2M aqueous H2SO4 are added to adjust the pH to 6.4. After stirring for 10 minutes the layers are separated (pH 6.4). 35mL of water are added to the CH2CI2 layer. Addition of 1.5mL of 2M aqueous H2SO4 gives a pH of 6.4. After stirring for 10 minutes the layers are separated. 8OmL of CH2CI2 are added to the combined aqueous layers. Addition of 2mL of 7M aqueous RG/G-50021-BCK9987NH3 gives a pH of 6.4 (after equilibration). The layers are separated. The combined organic layers are washed with 2OmL of water. The layers are separated. The combined CH2CI2 layer contains the enantiomerically enriched diol. The combined aqueous layer contains -90% of the chiral auxiliary. 20OmL of CH2Cl2 are removed. 6OmL of 2-propanol are added. 3OmL of 2-propanol / CH2CI2 are removed under reduced pressure. 3OmL of 2-propanol are added to obtain -13g of CIT-DIOL in 6OmL of ISO. To this solution 6.59g of (+)-ditoluoyl tartaric acid (MW: 386.36; assay: 99%; 17.1mmol, 0.45eq.), dissolved in 42mL of 2-propanol and 8mL of CH2CI2, are added. The product starts to crystallize after 5 minutes (or immediately after seeding). The mixture is stirred for 90 minutes at 35C, for 10 minutes at 600C and than slowly cooled down to room temperature (within ~5hours) and crystallized without stirring for 10 hours. The product is isolated by filtration to give 17.2g of S-CIT-DIOLlambda’ (+)-DTTA.lambda1 ISO.lambda1 H2O (yield: 81.0%; ee: 99.0%, assay: 61.0%) after drying for IOhours at 400C and 20mbar.

Statistics shows that 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile is playing an increasingly important role. we look forward to future research findings about 103146-25-4.

Reference:
Patent; SANDOZ AG; WO2007/82771; (2007); A1;,
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