Author: Jessica.F

Reference of 41789-95-1, A common heterocyclic compound, 41789-95-1, name is 1-(3-Methoxyphenyl)-N-methylmethanamine, molecular formula is C9H13NO, 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.

General procedure: A mixture of Pd(OAc)2 (6.7 mg, 0.030 mmol, 10 mmol%), Cu(OAc)2 (54.45 mg, 0.30 mmol, 1 equiv.), 1a (32.1 mg, 0.30 mmol, 1equiv.), CsF (136.7 mg, 0.90 mmol, 3 equiv.) was dissolved in a solvent of acetonitrile (3 mL) followed by addition of 2a (179 mg,0.60 mmol, 2 equiv.). The reaction mixture was stirred at 120 C for 24 h and progress of the reaction was monitored continuously byTLC with ethyl acetate: hexane eluent system. Upon completion of reaction the mixture was cooled to room temperature, poured into brine, and extracted with EtOAc. The combined extracts were dried over MgSO4 and filtered through pad of Celite eluting with ethylacetate. The filtrate was concentrated under reduced pressure and was purified by column chromatography (EtOAc/hexane) on silicagel to afford the 5,6-dihydrophenanthridine 3a. Compound 1i was synthesized in accordance with reported literature [25]. Characterization data of compounds 3a, 3c, and 3e were found exactly similar as reported in the literature (References of above compounds are mentioned in Supplementary data).

The synthetic route of 41789-95-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Asamdi, Manjoorahmed; Chauhan, Prakashsingh M.; Patel, Janki J.; Chikhalia, Kishor H.; Tetrahedron; vol. 75; 25; (2019); p. 3485 – 3494;,
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Electric Literature of 1758-46-9, 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. 1758-46-9, name is 2-Phenoxyethylamine, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of intermediate compound (prepared ac- cording to teachings in WO99/58530 of which the content is included herein) (0.025 mol) and 2-phenoxyethanamine (0.036 mol) in THF (300 ml) was hydrogenated at 140 °C for 16 hours with Pd/C 10 percent (3 g) as a catalyst in the presence of thiophene solution (3ml). After uptake of H2 (1 equivalent), the catalyst was filtered off and the filtrate was evaporated. The residue was triturated in 2-propanol. The precipitate was filtered off and dried. Yielding: 12.4 g of final compound 7 (94 percent).

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

Reference:
Patent; JANSSEN PHARMACEUTICA N.V.; WO2006/67139; (2006); A1;,
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Synthetic Route of 74654-07-2, 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. 74654-07-2 name is 2-(2-(2-Methoxyethoxy)ethoxy)ethanamine, 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.

Step a):Under inert atmosphere,5.00 g of 4-bromo-1,8-naphthalic anhydride was added to 100 mL of anhydrous methanol,1.96 g of 3,6,9-trioxa-1-aminodecane was further injected, and the mixture was refluxed for 10 hours.After the reaction was completed, overnight needle-like crystals were precipitated, filtered, washed with cold ethanol three times,The intermediate N-3,6,9-trioxadecyl-4-bromo-1,8-naphthalimide was obtained4.90 g (96% yield).

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

Reference:
Patent; Zhejiang Sci-Tech University; Han Yifeng; Chen Bo; Wei Ting; (13 pag.)CN105542756; (2017); B;,
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Reference of 31804-36-1, 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. 31804-36-1, name is 1-Bromo-3-methoxy-2-methylbenzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 4-bromo-l-methoxy-2-(3-methoxypropoxy)benzene (11.0 g, 54.7 mmol) in THF (120 mL) was added l-(2-thienyl)ethanone (8.97 g, 71.1 mmol), i-BuONa (7.89 g, 82.1 mmol), Pd2(dba)3 (1 g, 1.09 mmol) and Xantphos (633 mg, 1.09 mmol ) under nitrogen atmosphere. The mixture was heated at 50 C for 4 hrs, and then concentrated under reduced pressure. The residue was diluted with DCM (600 mL). The resulting organic mixture was washed with water and brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The residue was purified by column chromatography to afford 2-(3-methoxy-2-methyl- phenyl)-l-(2-thienyl)ethanone (13.0 g) as a brown oil.

The synthetic route of 1-Bromo-3-methoxy-2-methylbenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; HAN, Xingchun; JIANG, Min; YANG, Song; (109 pag.)WO2016/128335; (2016); A1;,
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Reference of 41864-45-3, These common heterocyclic compound, 41864-45-3, name is 4,5-Dimethoxy-2-methylaniline, 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.

The compound 63 (100 mg, 0.33 mmol) was dissolved in propionic acid (1 mL). 4,5-dimethoxy-2-methylaniline (223 mg, 1.33 mmol) was added to the solution. The mixture was stirred at 150C for 30 minutes. The reaction mixture was poured into ice water, and neutralized with the aqueous solution of sodium hydrogen carbonate. The mixture was extracted with ethyl acetate. The organic layer was washed by water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained oil was purified by silica-gel column chromatography (hexane-ethyl acetate). The obtained residue was solidified with ethyl acetate-hexane to give the compound 5 (66 mg, yield 47%). 1H-NMR (CDCl3) delta: 1.91 (s, 3H), 2.20 (s, 3H), 3.81 (s, 3H), 3.85 (s, 3H), 5.24 (br s, 2H), 5.38 (s, 1H), 6.26 (s, 1H), 6.70 (s, 1H), 6.50-6.85 (m, 2H), 7.52 (br s, 1H).

Statistics shows that 4,5-Dimethoxy-2-methylaniline is playing an increasingly important role. we look forward to future research findings about 41864-45-3.

Reference:
Patent; Shionogi & Co., Ltd; TANAKA, Satoru; OGAWA, Tomoyuki; KAI, Hiroyuki; OGATA, Yuki; HIRAI, Keiichiro; KUROSE, Noriyuki; FUJII, Yasuhiko; (438 pag.)EP3287443; (2018); A1;,
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Reference of 873980-68-8, 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 873980-68-8 as follows.

Preparation of 6-bromo-5-methybenzoxazole (43): To a suspension of 4-bromo-6-methoxy-3-methylaniline (41) (500 mg, 2.3 mmol) in 6 ml DCM was added 1 M BBr3 in DCM (4.6 ml, 4.6 mmol). The reaction mixture was stirred at r.t. for 2 h, which turned to a brown solution and back to a brown suspension. After quenched with aq. sodium bicarbonate solution, the mixture was extracted with EA. The org. phase was washed with brine, dried over sodium sulfate, concentrated to dryness to give 581 mg 2-amino-5-bromo-4-methylphenol as dark oil.A mixture of 2-amino-5-bromo-4-methylphenol (42) (290 mg), trifluoromethanesulfonic acidYtterbium (III) salt (20 mg) and trimethyl orthoformate (185 mul, 1.5 eq.) in 2 ml EtOH was heated at 90 C. for 2 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine, dried over Na2SO4, concentrated to dryness. The resulting brown solid was dissolved in DCM and subjected to silica gel column purification using 0-60% B (A: hexane; B: 50% EA in hexane) to furnish 91.9 mg 6-bromo-5-methylbenzoxazole (43) as yellow solid (yield: 38%)

According to the analysis of related databases, 873980-68-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CalciMedica, Inc.; US2011/263612; (2011); A1;,
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Some common heterocyclic compound, 19500-02-8, name is 3-Methoxy-2-methylaniline, molecular formula is C8H11NO, 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. SDS of cas: 19500-02-8

2-Methoxy-4-bromotoluene; Crude 2-methoxy-6-amino-toluene (max. 120 mmol) was suspended in HBr (48%, 48 ml) and water (120 ml) and cooled to 0C in an ice bath. Sodium nitrite (9.2 g) in water (24 ml) was added dropwise to the cold mixture, which turned yellow then brown. After 10 min, excess nitrite was destroyed by addition of urea (0.08 g) and the mixture was rapidly filtered into cold (0C) acetone (480 ml) to give a bright yellow solution. CuBr (99.999%, 18.89,131 mmol) was then added portionwise and the resulting mixture stirred at 0C for 3h. Gas evolution was observed. The mixture was allowed to warm to ambient temperature, and then concentrated in vacuo. Dichloromethane was then added and the mixture washed with sat. aq. sodium bicarbonate solution. The organic layer was separated, dried over magnesium sulphate and concentrated in vacuo to give the product (23.1 g, 96%) as a red oil. No.H (CDCl3; 250MHz) 7.18-6.77 (3H, m, aromatics), 3.83 (3H, s, OCH3), 2.32 (3H, s, CH3).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19500-02-8, its application will become more common.

Reference:
Patent; ARAKIS LTD.; WO2005/103019; (2005); A1;,
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22236-08-4, name is 3-(Difluoromethoxy)aniline, belongs to ethers-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. SDS of cas: 22236-08-4

To a solution of 3- (difluoromethoxy) aniline (318 mg, 2.0 iranol) and pyridine (633 mg, 8.0 iranol) in N-methylpyrrolidone (2 mL) was added phenyl chloroformate (251 muL, 2.0 mmol) under ice-cooling, and the mixture was stirred at room temperature for 2 hr. 2-chloro-4- [ (5-methyl-5H-pyrrolo [3, 2-d]pyrimidin-4- yl) oxy] aniline (275 mg, 1.0 mmol) was added to the reaction mixture, and the mixture was stirred at 800C for 8 hr. The reaction mixture was diluted with water, basified with IN aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane/ethyl acetate=80/20->0/100) , and then silica gel column chromatography (hexane/ethyl acetate=80/20-»0/100) and recrystallized from diisopropyl ether to give the title compound (229 mg, 50%) as a white solid. 1H-NMR (DMSO-de, 300 MHz) delta 4.11 (3H, s) , 6.61 (IH, d, J = 3.0 Hz), 6.81 (IH, dd, J = 8.0, 2.1 Hz), 7.19 – 7.23 (IH, m) , 7.22 (IH, t, J = 74.1 Hz), 7.31 (IH, dd, J = 9.0, 2.7 Hz), 7.35 (IH, t, J = 8.0 Hz), 7.49 (IH, t, J = 2.1 Hz), 7.56 (IH, d, J = 2.7 Hz), 7.80 (IH, d, J = 3.0 Hz), 8.17 (IH, d, J = 9.0 Hz), 8.30 (IH, s), 8.43 (IH, br s) , 9.60 (IH, br s) .

The synthetic route of 22236-08-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2007/4749; (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. 6781-17-5, name is 2-(2-Ethoxyphenoxy)ethanamine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 6781-17-5

EXAMPLE 1 A mixture of 1.9 g of 1-chloro-3-(4-fluorophenoxy)-propane, l.8 g of 2-(2-ethoxyphenoxy)ethylamine, 0.53 g of sodium carbonate and 60 ml of dimethylformamide was heated at 80-90 C for 15 hours. After cooling, the reaction mixture was poured into water and extracted with benzene. The extract was washed with water and dried over sodium sulfate and evaporated under reduced pressure. The oily residue was dissolved in ether and treated with ethanolic hydrogen chloride under cooling. The precipitate was collected by filtration and dried to give N-{2-(2-ethoxyphenoxy)ethyl}-3-(4-fluorophenoxy)propylamine hydrochloride, M.P. 78-82 C. Recrystallization from ethanol-benzene gave white crystals, M.P. 84-86 C.

According to the analysis of related databases, 6781-17-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sumitomo Chemical Company, Limited; US4010280; (1977); A;,
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Application of 393-15-7, A common heterocyclic compound, 393-15-7, name is 4-Methoxy-3-(trifluoromethyl)aniline, molecular formula is C8H8F3NO, 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.

General procedure: To a solution of N-[4-[5-(3-aminophenyl)-1,2,4-oxadiazol-3-yl]-3-chlorophenyl]-3-pyridinecarboxamide (VIc)(0.2 g, 0.51 mmol, 1 equiv) in THF (20 ml) was added phosgene(15wt % in toluene, 1.7 ml, 2.55 mmol, 5.0 equiv) and the reactionmixture was refluxed under N2 for 4 h. Upon the reactioncompletion as indicated by TLC the solution was concentratedunder reduced pressure, flushed with dry toluene. To theresulting residuewas added THF (20 ml), the appropriate aniline(0.77 mmol, 1.5 equiv) and DIPEA (0.132 g, 178 ml, 1.02 mmol, 2equiv) and the reaction mixture was refluxed under N2 overnight.Upon completion of the reaction as indicated by TLC, thesolution was concentrated, and the residue was purified bychromatography to give the desired final products (25-50).

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:
Article; Dokla, Eman M.E.; Fang, Chun-Sheng; Abouzid, Khaled A.M.; Chen, Ching S.; European Journal of Medicinal Chemistry; vol. 182; (2019);,
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