Month: June 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. 80936-82-9, name is 4-(Methoxymethyl)aniline, A new synthetic method of this compound is introduced below., Quality Control of 4-(Methoxymethyl)aniline

Example 82 Synthesis of 4-amino-1-(4,4-difluorocyclohexyl)-N-(4-(methoxymethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide 33 mg of methyl-4-amino-1-(4,4-difluorocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylate obtained in step 2 of Reference Example 10 was dissolved in 2 mL of methanol. 0.05 mL of a 5M aqueous sodium hydroxide solution was added thereto at room temperature, and the mixture was stirred at 60 C. for 1 hour. After cooling, 0.2 mL of a 5M aqueous hydrochloric acid solution was added, and the mixture was concentrated under reduced pressure. The obtained solid was suspended in 2 mL of DMF, and 17 mg of 4-(methoxymethyl)aniline, 60 mg of HATU, and 0.055 mL of N,N-diisopropylethylamine were added thereto at room temperature, followed by stirring at the same temperature for 1 hour. The reaction solution was diluted with ethyl acetate, and washed with water and a saturated aqueous sodium chloride solution. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The obtained residue was suspended in methanol, and filtered, followed by drying at 60 C. under reduced pressure, thereby obtaining 29 mg of the title compound.

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; TAIHO PHARMACEUTICAL CO., LTD.; MIYAZAKI, Isao; SHIMAMURA, Tadashi; KATO, Masanori; FUJITA, Hidenori; IGUCHI, Satoru; (161 pag.)US2018/9818; (2018); A1;,
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Reference of 645-36-3, A common heterocyclic compound, 645-36-3, name is 2,2-Diethoxyethanamine, molecular formula is C6H15NO2, 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 suspension of the appropriate quinolonecarboxylic acid (1mmol) in 6mL of dry THF at 25C, HOBt (1.5mmol), WSC (1.5mmol) and the appropriate aminoalcohol (1.5mmol) were added sequentially. The mixture was stirred at room temperature under nitrogen, then the solvent was evaporated, water was added and the solid formed filtered. The crude product was purified by flash chromatography.

The synthetic route of 645-36-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Cincinelli, Raffaella; Musso, Loana; Beretta, Giangiacomo; Dallavalle, Sabrina; Tetrahedron; vol. 70; 52; (2014); p. 9797 – 9804;,
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Synthetic Route of 17061-62-0,Some common heterocyclic compound, 17061-62-0, name is Bis(4-methoxybenzyl)amine, molecular formula is C16H19NO2, 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.

N,N-bis(4-methoxybenzyl)ethanesulfonamide, Example 12.0. To a solution of bis(4-methoxybenzyl)amine 12.01 (900 g, 3.49 mol, 1 eq) in DCM (9 L) was added TEA (634 mL, 4.55 mol, 1.3 eq), followed by dropwise addition of ethanesulfonyl chloride (399 mL, 4.19 mol, 1.2 eq). (The internal temperature was kept between 5-10 C during the addition of the ethane sulfonyl chloride). Once the addition was complete, the cooling bath was removed. After 1.5 h, TLC showed complete loss of starting material. The reaction was quenched by the addition of water (4 L) to the reaction mixture. The layers were separated and the aqueous layer extracted with DCM (2 x 2 L). The combined organic layers were washed with brine (2x 1 L), dried over Na2SO4, and concentrated in vacuo. The material thus obtained was adsorbed onto a plug of silica gel and purified by chromatography (silica gel (60-120 mesh) eluting with a gradient of 10- 80% EtOAc in hexanes) to provide the title compound 12.0 (1125 g, 3.22 mol, 92%) as white solid. ?H-NMR (400 MHz, CDC13) 7.23 (dd, J= 2.08, 6.62 Hz, 4H), 6.90 (dd, J= 2.12, 6.60 Hz, 4H), 4.29 (s, 4H), 3.83 (s, 6H), 2.92 (q, J 7.40 Hz, 2H), 1.33 (t, J 7.40 Hz, 3H). GC-MS (ESI pos. ion) m/z: 372.2 (M+Na).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Bis(4-methoxybenzyl)amine, its application will become more common.

Reference:
Patent; AMGEN INC.; CHEN, Ning; CHEN, Xiaoqi; CHEN, Yinhong; CHENG, Alan C.; CONNORS, Richard V.; DEIGNAN, Jeffrey; DRANSFIELD, Paul John; DU, Xiaohui; FU, Zice; HEATH, Julie Anne; HORNE, Daniel B.; HOUZE, Jonathan; KALLER, Matthew R.; KHAKOO, Aarif Yusuf; KOPECKY, David John; LAI, Su-Jen; MA, Zhihua; MCGEE, Lawrence R.; MEDINA, Julio C.; MIHALIC, Jeffrey T.; NISHIMURA, Nobuko; OLSON, Steven H.; PATTAROPONG, Vatee; SWAMINATH, Gayathri; WANG, Xiaodong; YANG, Kevin; YEH, Wen-Chen; DEBENEDETTO, Mikkel V.; FARRELL, Robert P.; HEDLEY, Simon J.; JUDD, Ted C.; KAYSER, Frank; (1266 pag.)WO2016/187308; (2016); 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. 36805-97-7, name is 1,1-Di-tert-butoxy-N,N-dimethylmethanamine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 1,1-Di-tert-butoxy-N,N-dimethylmethanamine

[0403] To a solution of 5-acetyl-N-(2,6-diethylphenyl)-1-methyl-1H-pyrazole-3-carboxamide (0.013 g, 0.043 mmol) in DMF (1.5 mL), N,N-dimethylformamide di-tertbutyl acetal (0.0.63 mL, 0.650 mmol) was added. The mixture was stirred at 80 C. for 2 h. The reaction was diluted with water, extracted with AcOEt (2×20 mL). The organic fractions were combined, dried over Na2SO4, filtered, and concentrated in vacuo and the residue used without any further purification. (0.017 g, 78% yield). [0404] 1H NMR (400 MHz, DMSO-d6) delta ppm 9.58 (s, 1H), 7.71 (d, J=12.33 Hz, 1H), 7.36 (s, 1H), 7.21 (t, J=7.60 Hz, 1H), 7.12 (d, J=7.60 Hz, 2H), 5.75 (d, J=12.33 Hz, 1H), 4.18 (s, 3H), 3.16 (s, 3H), 2.92 (s, 3H), 2.52 (q, J=7.57 Hz, 4H), 1.09 (t, J=7.57 Hz, 6H) [0405] HRMS (ESI) calcd for C20H27N4O2 [M+H]+ 355.2129. found 355.2133.

According to the analysis of related databases, 36805-97-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NERVIANO MEDICAL SCIENCES S.R.L.; Casuscelli, Francesco; Brasca, Maria Gabriella; Caldarelli, Marina; Cervi, Giovanni; Disingrini, Teresa; Quartieri, Francesca; US2014/51708; (2014); A1;,
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Some common heterocyclic compound, 126829-31-0, name is 2-Ethynyl-1,3-dimethoxybenzene, molecular formula is C10H10O2, 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. Formula: C10H10O2

General procedure: 1 ethynyl 2-methoxybenzene (2a) (265 mg, 2 mmol) and phenylazide (238 mg, 2 mmol) were added in 8 mL of a water and tertbutanol(1:1) mixture. Then 200 mL of freshly prepared 1 M aq.solution of sodium ascorbate (0.2 mmol) was added, following theaddition of 65 mL of aq. CuSO4*5H20 (5 mg, 0.02 mmol) solution. Thereaction mixture was stirred for approximately 14 h at room temperatureand reaction progress was monitored by TLC until its reactantswere completely consumed. Then 30 mL of ice cold waterwas poured into the reaction mixture and flask put in ice bath for15 min following the filtration to get white precipitate that werethoroughly rinsed with cold water (2 x 15 mL). The collected solidwas dried under vacuum to get pure product [23,24].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 126829-31-0, its application will become more common.

Reference:
Article; Jabeen, Sobia; Khera, Rasheed Ahmad; Iqbal, Javed; Asgher, Muhammad; Journal of Molecular Structure; vol. 1206; (2020);,
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Adding a certain compound to certain chemical reactions, such as: 6358-77-6, name is 5-Bromo-2-methoxyaniline, belongs to ethers-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 6358-77-6, name: 5-Bromo-2-methoxyaniline

N, N-DIISOPROPYLETHYLAMINE (13.49 ml, 77.4 mmol) and methyl bromoacetate (0.95 eq, 49.0 mmol) were added to a solution of 5-bromo-2-methoxyaniline (1 eq, 51.6 mmol) in anhydrous DMF (100 ml) under nitrogen. The solution was heated for 16 hours at 60 C before cooling to ambient temperature. DMF was removed under reduced pressure. The residue was dissolved in 500 ml of DCM, washed with 2 x 200 ml of water, was dried over sodium sulfate and was filtered and concentrated under reduced pressure. The title compound was precipitated from DCM/hexanes as an off-white, brownish solid (10.34 G)

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2004/41799; (2004); A1;,
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Reference of 74654-07-2, These common heterocyclic compound, 74654-07-2, name is 2-(2-(2-Methoxyethoxy)ethoxy)ethanamine, 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-(3,4-Dichlorophenyl)-N-{(l S)-2-((3S)-3-hydroxypyrrolidin-l -yl)-l – phenylethyl}-N-methylacetamide (3) (0.030 g, 0.074 mmol) and 4-nitrophenyl carbonochloride (0.017 g, 0.081 mmol) were dissolved in 3 mL of dichloromethane. N,N- diisopropylethylamine (0.018 g, 0.15 mmol) was added under stirring. The reaction mixture was stirred at room temperature for two hours. 2-(2-(2-methoxyethoxy)ethoxy)ethanamine (0.033 g, 0.20 mmol) was added. The reaction mixture was stirred at room temperature for 6 hours. 100 mL of dichloromethane was added into the reaction mixture. The resultant solution was washed with saturated sodium chloride (60 mL chi 3) and was dried over sodium sulfate. Evaporation of the solvent and purification of the residue by flash chromatography yielded (35)-l -[(21S)-2-{[(3,4-Dichlorophenyl)acetyl](methyl)amino}-2- phenylethyl]pyrrolidin-3-yl {2-[2-(2-methoxyethoxy)ethoxy]ethyl} carbamate (0.023 g, 58% yield). NMR (500 MHz, CDC13): delta 7.45-7.26 (m, 7H), 7.16 (m, 1 H), 6.10 (m, 0.85H), 5.20 (m, 2H), 5.05 (m, 0.15H), 3.85-3.62 (m, 10H), 3.57 (m, 4H), 3.38 (s, 3H), 3.15 (t, 1 H), 2.98 (m, 2H), 2.75 (m, 4H), 2.40 (m, 1H), 2.20 (m, 1 H), 1.82 (m, 2H); MS (EI) for C29H39C12N306: 596 (MH+).

Statistics shows that 2-(2-(2-Methoxyethoxy)ethoxy)ethanamine is playing an increasingly important role. we look forward to future research findings about 74654-07-2.

Reference:
Patent; NEKTAR THERAPEUTICS; ANAND, Neel, K.; DUARTE, Franco, J.; ZHANG, Wen; REN, Zhongxu; WO2014/210436; (2014); A2;,
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Some common heterocyclic compound, 50742-37-5, name is (3-Phenoxyphenyl)methanamine, molecular formula is C13H13NO, 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: (3-Phenoxyphenyl)methanamine

Example 17 – 3-[(Z)-2-Chloro-3,3,3-trifluoro-prop-1-enyl]-2,2-dimethyl-N-[(3-phenoxyphenyl) methyl]cyclopropanecarboxamide 55 A solution of 3-[(Z)-2-chloro-3,3,3-trifluoro-prop-1-enyl]-2,2-dimethyl-cyclopropanecarbonyl chloride (100mg, 1.1 eq) in toluene (6ml_) was added dropwise to a solution of (3- phenoxyphenyl)methanamine (170mg, 1 eq) and pyridine (68muIota_, 1 eq) in toluene (6ml_). The reaction mixture was stirred overnight at room temperature after which time TLC analysis showed the reaction had gone to completion. The reaction mixture was diluted with ethyl acetate (15ml_) and washed with water (2 x 10ml_) and brine (10ml_) before being dried over MgS04 and the solvent removed in vacuo. The residue was purified by flash chromatography (solvent 9: 1 hexane/ethyl acetate) to afford the product as a clear oil (86mg, 24 %). 1 H NMR deltaEta (CDCIs, 300 MHz): 7.22 (m, 3H), 7.04 (m, 2H), 6.94 (m, 3H), 6.84 (m, 2H), 5.78 (s, 1 H), 4.33 (ddd, J= 20.7, 15.0, 5.7 Hz, 2 H), 1.99 (m, 2 H), 1.21 (s, 3H), 1.19 (s, 3H); ESI-MS 424.2 [MH]+..

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 50742-37-5, its application will become more common.

Reference:
Patent; REDX PHARMA LIMITED; THOMPSON, William; JACKSON, Peter; LINDSAY, Derek; SCREEN, Thomas; MOLTON, Benjamin; URCH, Christopher; WO2013/136073; (2013); A1;,
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Synthetic Route of 92248-06-1,Some common heterocyclic compound, 92248-06-1, name is Bis(3-methoxyphenyl)amine, molecular formula is C14H15NO2, 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.

Under a nitrogen atmosphere,Adding 2,2′-dibromo-9,9′-spirobifluorene (0.7 g, 1.48 mmol),Bis (3-methoxyphenyl) amine (1.01 g, 4.44 mmol),Palladium acetate (18mg, 0.082mmol),Cesium carbonate (1.74g, 5.33mmol)And tri-tert-butylphosphine (0.038mL, 0.15mmol) in toluene(10mL) mixed well in the solution,Heat and stir at 110 C for 20 hours.After cooling to room temperature,The reaction was quenched with a saturated ammonium chloride solution.The aqueous layer was extracted three times with ethyl acetate,Use up the combined organic phasesAnd washed with aqueous sodium chloride.After the organic phase was dried over anhydrous sodium sulfate,The solvent was evaporated to dryness under reduced pressure,The obtained product was further purified by silica gel column chromatography,Petroleum ether / ethyl acetate (10: 1, v / v) was used as the eluent.Get pure product,As a white solid.Yield: 95% (1.08 g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Bis(3-methoxyphenyl)amine, its application will become more common.

Reference:
Patent; Nanjing Tech University; Hang Xiaochun; Qian Chunyue; Huang Wei; Shen Kang; Qin Tianshi; (57 pag.)CN110790629; (2020); A;,
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19500-02-8, name is 3-Methoxy-2-methylaniline, 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. Application In Synthesis of 3-Methoxy-2-methylaniline

General procedure: Ammonium thiocyanate was added to a solution of aniline in 1.0 N HCl(aq). The reaction was stirred at 100 C for 16 h-20 h,cooled to room temperature over 1 h, diluted with cold water(30 mL), and then neutralized with saturated NH4OH(aq) (pH > 7).The precipitatewas collected by vacuum filtration andwashed withwater and diethyl ether: n-hexanes (1: 3) to give the desiredproduct. The product was purified by Isco Combi-Flash Companioncolumn chromatography.

The synthetic route of 19500-02-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Lin, Shu-Yu; Kuo, Yu-Hsien; Tien, Ya-Wen; Ke, Yi-Yu; Chang, Wan-Ting; Chang, Hsiao-Fu; Ou, Li-Chin; Law, Ping-Yee; Xi, Jing-Hua; Tao, Pao-Luh; Loh, Horace H.; Chao, Yu-Sheng; Shih, Chuan; Chen, Chiung-Tong; Yeh, Shiu-Hwa; Ueng, Shau-Hua; European Journal of Medicinal Chemistry; vol. 167; (2019); p. 312 – 323;,
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