Tag: M.W=100-200

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. 41429-22-5, name is 2-(2-(Difluoromethoxy)phenyl)acetonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Formula: C9H7F2NO

[0607] To a solution of [2-(difluoromethoxy)phenyl]acetonitrile (5.00 g, 27.3 mmol) in THF (25 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (16 ml, 33 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, a solution of tert-butyl 3-bromopropanoate (5.2 ml, 33 mmol) in THF (10 ml) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water and ethyl acetate (100 ml of each) were gradually added at about 0C. to the mixture, which was agitated. After phase separation, the aqueous phase was extracted once with ethyl acetate (100 ml). The combined organic phases were washed once with saturated aqueous sodium chloride solution (150 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (100 g silica gel Biotage Snap-Cartridge Ultra, cyclohexane/ethyl acetate gradient 93:7?7:3, Isolera One). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 3.85 g (83% purity, 38% of theory) of the title compound. [0608] LC-MS (Method 1): Rt=2.10 min; MS (ESIpos): m/z=312 [M+H]+

The synthetic route of 41429-22-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bayer Aktiengesellschaft; Bayer Pharma Aktiengeseiisehaft; BECK, Hartmut; KAST, Raimund; MEININGHAUS, Mark; DIETZ, Lisa; FUERSTNER, Chantal; STELLFELD, Timo; ANLAUF, Sonja; VON BUEHLER, Clemens-Jeremias; BAIRLEIN, Michaela; ANLAHR, Johanna; MUENSTER, Uwe; TERJUNG, Carsten; JOERISSEN, Hannah; HAUFF, Peter; MUELLER, Joerg; DROEBNER, Karoline; NAGEL, Jens; (220 pag.)US2020/31775; (2020); A1;,
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191014-55-8, name is 4-Fluoro-2-methoxybenzonitrile, 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. Computed Properties of C8H6FNO

Pyrazolospiroketone Preparation 11; 2-Methoxy-4-(3′-methyl-7′-oxo-6′.7′-dihvdro-2’H-spirorpiperidine-4,5′-pyranor3.2-clPyrazol1-2′-; To a solution of 4-fluoro-2-methoxybenzonitrile (100 g, 0.662 mol) in ethanol (0.66 L) was added hydrazine monohydrate (331 g, 0.321 L, 6.62 mol). The mixture was heated at reflux overnight. The reaction was cooled to room temperature, diluted with water (750 mL), stirred for 1.5 hours and the resulting solids were collected by filtration. The solids were rinsed with water (2 x 250 mL) and air dried for 3 hours. The solids were then dried in a vacuum oven at 45 QC. The material was dissolved in dioxane (2 L) and HCI gas was bubbled through for 30 minutes. The resulting solids were filtered and washed with methyl tert-butyl ether (2 x 1 L). The solids were air dried for 1 hour and the resulting solids were dried in a vacuum oven at 45 QC to provide -hydrazino-2-methoxybenzonitrile hydrochloride (115.6 g, 87.5%).

The synthetic route of 191014-55-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER, INC.; WO2009/144554; (2009); A1;,
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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. 180976-09-4, name is tert-Butyl (cyanomethyl)(methyl)carbamate, A new synthetic method of this compound is introduced below., SDS of cas: 180976-09-4

Preparation of tert-butyl (1-cyano-2-(4-fluorophenyl)ethyl)(methyl)carbamate 1-9 [0119] A mixture of tert-butyl (cyanomethyl)(methyl)carbamate (500 mg, 2.94 mmol) in THF (3 mL) was stirred at -78 oC under N2. LDA (2.203 ml, 4.41 mmol) and DMPU (1.417 ml, 11.75 mmol) were added dropwise at -78 oC. The reaction mixture was stirred at this temperature for 1 h. 1-8 (833 mg, 4.41 mmol) was added dropwise at -78 oC. The mixture was stirred at -78 oC for 1 h. The mixture was diluted with EtOAc (100 mL), washed with aq. NH4Cl (100 mL), dried over Na2SO4, filtered and the solvent was evaporated under reduced pressure. The residue was purified by prep-TLC (PE: EA = 10:1) to give 1-9. [0120] 1H NMR (CDCl3, 400 MHz) delta 7.177.02 (m, 2H), 7.006.98 (m, 2H), 5.355.02 (m, 1H), 3.112.90 (m, 5H), 1.561.42 (m, 9H).

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; MERCK SHARP & DOHME CORP.; ROECKER, Anthony, J.; LAYTON, Mark, E.; GRESHOCK, Thomas, J.; PERO, Joseph, E.; KELLY, Michael, J., III; ZHANG, Ting; (75 pag.)WO2017/165204; (2017); A1;,
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Application of 13726-21-1, 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. 13726-21-1, name is 2-(4-Chloro-3-methoxyphenyl)acetonitrile, This compound has unique chemical properties. The synthetic route is as follows.

KOtBu (370 g, 3.3 mol) was dissolved in THF (1.7 L) and stirred at -20 C. After 30 min, to the reaction mixture was added 2-(4-chloro-3-methoxyphenyl)acetonitrile (13) (240 g, 1.32 mol) in THF (0.5 L) and then the resulting mixture was stirred for additional 30 min at the same temperature. CH3I (563 g, 3.96 mol) was added and the mixture was slowly warm to room temperature over 2 h with mechanical stirring. The reaction mixture was quenched with water in ice-bath and extracted with EtOAc (1.5 L x 2). The combined organic layers were washed with brine (3 L), dried over anhydrous MgS04, filtered and concentrated under reduced pressure to give 2-(4-chloro-3-methoxyphenyl)-2-methylpropanenitrile (14) as a amber liquid (269 g, 97%). 1H NMR (400MHz, CDC13): delta 7.35-7.37 (d, 1H), 7.05 (s, 1H), 6.95-6.97 (d, 1H), 3.94 (s, 3H), 1.72 (s, 6H).

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

Reference:
Patent; EXELIXIS, INC.; BOLLU, Venkataiah; BOREN, Brant, Clayton; DALGARD, Jackline; FLATT, Brenton, T.; HAQ, Nadia; HUDSON, Sarah; MOHAN, Raju; MORRISSEY, Michael; PRATT, Benjamin; WO2011/71565; (2011); A1;,
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Related Products of 86770-80-1, 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. 86770-80-1, name is 3,3-Difluorocyclobutanecarbonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 125C 3,3-difluoro-1-(4-(trifluoromethyl)pyridin-2-yl)cyclobutanecarbonitrile Example 125B and 2-fluoro-4-(trifluoromethyl)pyridine (0.900 mL, 7.39 mmol) were dissolved in toluene (2.4 mL), cooled to <5 C. and added KHMDS (29.6 mL, 14.78 mmol) dropwise, allowed to warm slowly to room temperature and stirred for 90 minutes. The mixture was diluted with MTBE and washed with water (2*). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was chromatographed on silica gel (0-25% EtOAc/hexanes) to provide Example 125C (1.22 g, 4.65 mmol, 63.0% yield). 1H NMR (300 MHz, DMSO-d6) delta 9.00-8.94 (m, 1H), 8.04-7.99 (m, 1H), 7.88 (ddd, J=5.1, 1.6, 0.8 Hz, 1H), 3.68-3.48 (m, 5H). The synthetic route of 3,3-Difluorocyclobutanecarbonitrile 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.; Dart, Michael J.; Gfesser, Gregory A.; Gomtsyan, Arthur; Kort, Michael E.; Kym, Philip R.; Schmidt, Robert G.; Voight, Eric A.; US2014/80803; (2014); A1;,
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Reference of 251570-03-3, 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. 251570-03-3 name is 2-(4-Chloro-3-fluorophenyl)acetonitrile, 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.

A mixture of the product of example 22 (7.8g, 0.046 mol), water (7.5 ml), concentrated sulfuric acid (7.5ml) and acetic acid (7.5ml) was heated at reflux for 2 hours . After being cooled to room temperature, the mixture was poured into ice-water. The resulting solids were collected by filtration and washed by diethyl ether to give the titled product (6.8g, 79%)1H NMR (300 MHz, DMSO-/) 3.64 (s, 2H), 7.14 (ddd, J= 0.6, 2.1, 8.2 Hz, IH), 7.34 (dd, J= 2.1, 10.6 Hz, IH), 7.52 (t, J=8.1 Hz, IH).MS (ESI”) m/z 187 (M-I)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(4-Chloro-3-fluorophenyl)acetonitrile, and friends who are interested can also refer to it.

Reference:
Patent; AVEXA LIMITED; DEADMAN, John, Joseph; JONES, Eric, Dale; LE, Giang, Thanh; RHODES, David, Ian; THIENTHONG, Neeranat; VAN DE GRAFF, Nicholas, Andrew; WINFIELD, Lisa, Jane; WO2010/31; (2010); A1;,
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Electric Literature of 72635-78-0,Some common heterocyclic compound, 72635-78-0, name is 3-Amino-4-bromobenzonitrile, molecular formula is C7H5BrN2, 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.

4-Bromo-3-chlorobenzonitrile (60c). Aniline 56 (5.19 g, 26.4 mmol) was added to conc. HCl maintained below 0 C. A solution of sodium nitrite (3.67 g, 53.2 mmol) in water (10 mL) was added dropwise such that the temperature of the reaction mixture did not exceed 5 C. The mixture was maintained for 1 h, then was added to a solution of CuCl (6.55 g, 66.2 mmol) in conc. HCl (20 mL). Toluene (200 mL) was added, and the biphasic mixture was stirred at 60-80 C for 1 h. Layers were separated, and the aqueous layer was extracted into toluene to afford a white solid (4.67 g, 82%); mp 80-81 C (hexane); 1H NMR delta 9.55 (d, J = 1.8 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 and 1.9 Hz, 1 H); HPLC (Method B) tR 3.96 min (100 area % at 265 nm). Anal. (C7H3BrClN) C, H, N, Br, Cl.; Reagents and conditions: (a) fuming HNO3, H2SO4; (b) Fe, AcOH, EtOH; (c) NaNO2, aq. HCl, then CuCl; (d) NalO4, l2, AcOH, AC2O, H2SO4; (e) NH2OH HCl, Py, EtOH (f) Ac2O; (g) TMSA, Pd2Cl2(PPh3)2, Cul, Et3N; (h) TMSA, PPh3, Pd(PPh3)4, Cul, piperidine; (j) 2-methyl-3-butyn-2-ol, Pd2Cl2(PPh3)2, Cul, Et3N; (k) 2-methyl-3-butyn-2-ol, 10% Pd/C, PPh3, Cul, aq. K2CO3/DME; (I) Cs2CO3, aq. CH3CN or MeOH; (m) NaH, toluene.; A second general method is depicted in Scheme 2 immediately hereinabove and comprises the cycloaddition of cyanophenylacetylenes 51 and benzaldehyde chlorooximes 52 in the presence of bis(tributyltin) oxide, see Moriya, O., et al., J. Chem. Soc., Perkin Trans., 1, 413-417 (1994); Moriya, O., et al., J. Chem. Soc., Chem. Commun., 17-18 (1991), or triethylamine, see Thomsen, l., et al., Acta Chem. Scand. (B), 319-313 (1988), in nonpolar solvents to give isoxazole dinitriles 53a-h,k-s and bromonitrile 53i. The latter was treated with copper(I) cyanide to give dinitrile 53j. See Friedman. L., et al., J. Org. Chem., 26, 2522-2524 (1961). This method also afforded alternate routes to dinitriles 50a,b,g, k prepared by the first method as provided in Scheme 1. The phenylacetylene synthons 51a-g were prepared as shown in Scheme 3 below. Starting materials 60a,e,g were commercially available. Nitration of 60a gave 60b. See Borsche, W., L., et al., Chem. Ber., 49, 2222-2243 (1916). The latter was reduced to aniline 56, see Blanksma, J. J., et al., Recl. Trav. Chim. Pays-Bas, 66, 365-373 (1947), which underwent diazotization followed by treatment with copper(l) chloride to give chlorobenzene 60c. Triflate 60d was prepared by treatment of 4-bromo-3-hydroxybenzonitrile with triflic anhydride. The preparation of aryl iodide 60f began with the known transformation of aldehyde 57 to iodo derivative 58. See Lulinski, P., et al., Bull. Chem. Soc. Jpn., 73(4), 951-956 (2000). Treatment of 58 with hydroxylamine hydrochloride gave aldoxime 59, which was dehydrated to give nitrile 60f using acetic anhydride. The aryl halides or triflates 60a-g were treated with (trimethylsilyl)acetylene, see Roesch. K. R., et al., J. Org. Chem., 66, 412-420 (2001), or with 2-methyl-3-butyn-2-ol, see Bleicher, L. S., et al., J. Org. Chem., 63, 1109-1118 (1998), to give intermediates 61a-f or 62a-f, respectively, of which 61a,d and 62a have been reported previously. See Dirk. S. M., et al., Tetrahedron, 59(3), 287-293 (2003); Bleicher, L. S., et al., J. Org. Chem., 63, 1109-1118 (1998). The acetylenes 51 (of which 51a,e were known previously), see Blackburn, B. K., et al., J. Med. Chem., 40(5), 717-729 (1997); Dulog, L., et al., Liebigs Ann. Chem., 9, 1663-1671 (1995), were obtained by the treatment of intermediates 61 or 62 with cesium carbonate in acetonitrile or sodium hydride in toluene, respectively. See Bleicher, L. S., et al., J. Org. Chem., 63, 1109-1118 (1998). The use of cesium carbonate in acetonitrile was introduced for the deprotection of intermediates 61 after the treatment of compound 61b with potassium carbonate in methanol, see Blackburn, B. K., et al., J. Med. Chem., 40(5), 717-729 (1997), failed to give product 51b. The pathway using 2-methyl-3-butyn-2-ol provided more economical preparations of all phenylacetylenes 51 except nitro analog 51b.

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-4-bromobenzonitrile, its application will become more common.

Reference:
Patent; THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL; EP1719767; (2006); A1;,
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Adding a certain compound to certain chemical reactions, such as: 500912-18-5, name is 2-(2-Fluoro-6-methoxyphenyl)acetonitrile, 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 500912-18-5, name: 2-(2-Fluoro-6-methoxyphenyl)acetonitrile

[0428] Under argon and at -78C., a mixture of 2.5 M butyllithium solution in hexane (13 ml, 33 mmol) and THF (50 ml) was added slowly to a solution of N,N-diisopropylethylamine (5.8 ml, 33 mmol) in THF (75 ml). The reaction mixture was allowed to warm to 0C., stirred at 0C. for 5 min and cooled back down again to -78C. A solution of (2-fluoro-6-methoxyphenyl)acetonitrile (5.00 g, 30.3 mmol, CAS-RN 500912-18-5, commercially available) in THF (25 ml) was then added slowly. The reaction mixture was once more allowed to warm to 0C., stirred at 0C. for 5 min and cooled back down again to -78C. A solution of iodomethane (2.0 ml, 31.79 mmol) in THF (25 ml) was then added slowly. The mixture was stirred overnight, with the temperature gradually rising to RT. At 0C., saturated ammonium chloride solution and water (50 ml each) were then added and the mixture was shaken and extracted twice with ethyl acetate (150 ml each). The combined organic phases were washed once with saturated aqueous sodium chloride solution (200 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (400 g of silica gel Buchi Snap-Cartridge KP-Sil, cyclohexane/ ethyl acetate 9:1). The combined target fractions were concentrated, and the residue was (briefly) dried under reduced pressure. This gave 3.33 g (100% purity, 61% of theory) of the title compound. [0429] GC-MS (Method 12): Rt=4.31 min; MS (ESIpos): m/z=179 [M]+ [0430] 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 1.492 (15.85), 1.509 (16.00), 3.314 (9.13), 3.887 (0.90), 4.452 (0.69), 4.455 (0.70), 4.470 (2.12), 4.473 (2.10), 4.488 (2.11), 4.491 (2.05), 4.505 (0.69), 4.508 (0.65), 6.861 (1.62), 6.863 (1.60), 6.884 (2.45), 6.907 (1.81), 6.909 (1.81), 6.943 (3.36), 6.964 (3.72), 7.353 (1.56), 7.370 (1.87), 7.374 (2.99), 7.391 (3.02), 7.395 (1.60), 7.412 (1.36). [0431] 1H-NMR (400 MHz, DMSO-d6): 5 [ppm]=7.44-7.30 (m, 1H), 6.95 (d, 1H), 6.92-6.85 (m, 1H), 4.48 (qd, 1H), 3.88 (s, 3H), 1.50 (d,3H).

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, 2-(2-Fluoro-6-methoxyphenyl)acetonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Bayer Aktiengesellschaft; Bayer Pharma Aktiengeseiisehaft; BECK, Hartmut; KAST, Raimund; MEININGHAUS, Mark; DIETZ, Lisa; FUERSTNER, Chantal; STELLFELD, Timo; ANLAUF, Sonja; VON BUEHLER, Clemens-Jeremias; BAIRLEIN, Michaela; ANLAHR, Johanna; MUENSTER, Uwe; TERJUNG, Carsten; JOERISSEN, Hannah; HAUFF, Peter; MUELLER, Joerg; DROEBNER, Karoline; NAGEL, Jens; (220 pag.)US2020/31775; (2020); A1;,
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Related Products of 13726-21-1, These common heterocyclic compound, 13726-21-1, name is 2-(4-Chloro-3-methoxyphenyl)acetonitrile, 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.

BBr3 (17 g, 66 mmol) was slowly added to a solution of 2-(4-chloro-3-methoxyphenyl)acetonitrile (12 g, 66 mmol) in dichloromethane (120 mL) at -78 C. under N2. The reaction temperature was slowly increased to room temperature. The reaction mixture was stirred overnight and then poured into ice and water. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (40 mL*3). The combined organic layers were washed with water, brine, dried over Na2SO4, and concentrated under vacuum to give (4-chloro-3-hydroxy-phenyl)-acetonitrile (9.3 g, 85%). 1H NMR (300 MHz, CDCl3) delta 7.34 (d, J=8.4 Hz, 1H), 7.02 (d, J=2.1 Hz, 1H), 6.87 (dd, J=2.1, 8.4 Hz, 1H), 5.15 (brs, 1H), 3.72 (s, 2H).

Statistics shows that 2-(4-Chloro-3-methoxyphenyl)acetonitrile is playing an increasingly important role. we look forward to future research findings about 13726-21-1.

Reference:
Patent; Vertex Pharmaceuticals Incorporated; Van Goor, Fredrick F.; Burton, William Lawrence; US2015/231142; (2015); A1;,
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Synthetic Route of 36764-94-0, 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 36764-94-0 as follows.

General procedure: A solution of 2,4,6-trisubstitutedphenylamine (10, 0.8 mmol) in pyridine (10 mL) was added to the flask containingt he crude acyl chloride 8 (0.8 mmol) which was prepared from the procedure described above, and the mixture was refluxed for 3-5 h. After cooling down, the mixture was poured into water (50 mL) and extracted with ethyl acetate (3× 15 mL). The extracts were combined and washed with hydrochloric acid (2 × 10 mL) and brine, successively. The organic phase was dried over anhydrous Na2SO4. After solvent removal, the residue was further purified by recrystallization from ethanol to afford the title compound 12(a-c) as a solid.

According to the analysis of related databases, 36764-94-0, the application of this compound in the production field has become more and more popular.

Reference:
Article; Wang, Baolei; Wang, Hongxue; Liu, Hang; Xiong, Lixia; Yang, Na; Zhang, Yan; Li, Zhengming; Chinese Chemical Letters; vol. 31; 3; (2020); p. 739 – 745;,
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