Author: Jessica.F

These common heterocyclic compound, 109-85-3, name is 2-Methoxyethylamine, 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. Recommanded Product: 2-Methoxyethylamine

A solution of 6-amino-4-fluoronicotinonitrile (obtained in step 9, 1 .10 g, 8.02 mmol) in DMA (20 mL) was treated with 2-methoxyethylamine (2.07 mL, 24.1 mmol) and DIPEA (4.20 mL, 24.1 mmol), heated to 50 C and stirred for 15 h. The reaction mixture was cooled to room temperature and concentrated. The crude material was purified by normal phase chromatography (24 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated and dried under vacuum to give the title compound as an off-white solid

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

Reference:
Patent; NOVARTIS AG; BUSCHMANN, Nicole; FAIRHURST, Robin Alec; FURET, Pascal; KNOEPFEL, Thomas; LEBLANC, Catherine; MAH, Robert; MALLET, Franck; MARTZ, Julie; LIAO, Lv; XIONG, Jing; HAN, Bo; WANG, Can; ZHAO, Xianglin; (56 pag.)WO2016/151500; (2016); A1;,
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These common heterocyclic compound, 107622-80-0, name is (4-Phenoxyphenyl)methanamine, 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. name: (4-Phenoxyphenyl)methanamine

General procedure: One equivalent of intermediate 14a or 14b was dissolved in THF and 1.5 eq of the proper amine, 1.5 eq of TEA, 1.5 eq of NaI and 0.3 eq of (CH3COO)2Pd were added to this solution. The reaction was conducted under muW, at 100C, for 20min. The resulting mixture was filtered through Celite, dried in vacuo and reconstituted in DCM. The organic phase was washed with water (3×50mL), dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using DCM/MeOH (9:1 v/v) as mobile phase giving derivative 15 in 38% yield and intermediates 16a-i in 55-75% yield.

The synthetic route of (4-Phenoxyphenyl)methanamine has been constantly updated, and we look forward to future research findings.

Reference:
Article; Musella, Simona; di Sarno, Veronica; Ciaglia, Tania; Sala, Marina; Spensiero, Antonia; Scala, Maria Carmina; Ostacolo, Carmine; Andrei, Graciela; Balzarini, Jan; Snoeck, Robert; Novellino, Ettore; Campiglia, Pietro; Bertamino, Alessia; Gomez-Monterrey, Isabel M.; European Journal of Medicinal Chemistry; vol. 124; (2016); p. 773 – 781;,
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Application of 363-47-3, A common heterocyclic compound, 363-47-3, name is 3,5-Difluoro-4-methoxyaniline, molecular formula is C7H7F2NO, 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.

A solution of 3,5-difluoro-4-methoxyaniline (100 mg, 0.628 mmol) and triethylamine (131 mul, 0.943 mmol) in DCM was coiled and added 2-chloroacetyl chloride (60.0 mul, 0.754 mmol). The reaction mixture was stirred at room temperature for 2 h. Reaction was diluted with DCM, washed with 0.5 M HCl, water, brine, dried over Na2SO4 and evaporated. The crude brown solid, 2-chloro-N-(3,5-difluoro-4-methoxyphenyl)acetamide (120 mg, 0.509 mmol, 81% yield) was used for the next step without purification. 1H-NMR (400 MHz, CDCl3) delta ppm 8.15 (s, 1H), 7.21 (d, 1H, J=8 Hz), 4.18 (s, 1H), 3.97 (s, 3H); ESI-MS: m/z 235.82 (M+H)+.

The synthetic route of 363-47-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Stingray Therapeutics, Inc.; Vankayalapati, Hariprasad; Sharma, Sunil; Kaadige, Mohan Rao; Weston, Alexis; Thode, Trason; (117 pag.)US2020/39979; (2020); A1;,
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Some common heterocyclic compound, 352-67-0, name is 1-Fluoro-4-(trifluoromethoxy)benzene, molecular formula is C7H4F4O, 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. COA of Formula: C7H4F4O

EXAMPLE 49 3-Trifluoromethoxy-10-methyl-9H-imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine; a) 2-Fluoro-5-trifluoromethoxy-benzaldehyde; A solution of 1-fluoro-4-trifluoromethoxy-benzene (21.0 g, 117 mmol) in THF (233 ml) was cooled to <-70 C. Tert.-butyllithium (86 ml of a 1.5 molar solution in pentane, 129 mmol) was added at such a rate that temperature was kept <-70 C. Stirring in the dry ice bath was continued for 15 min, then DMF (11.6 ml, 150 mmol) was added dropwise keeping temperature <-70 C. After 30 min the reaction mixture was allowed to reach rt, quenched with saturated NH4Cl solution and extracted with ether. The organic phase was washed with brine, concentrated and chromatographed (SiO2, heptane:ethyl acetate=100:0 to 80:2). The title compound (11.0 g, 53%) was obtained as a light yellow oil. 1H-NMR (300 MHz, DMSO): delta=7.60 (t, J=9.2 Hz, 1H), 7.75-7.85 (m, 2H), 10.20 (s, 1H). These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 352-67-0, its application will become more common. Reference:
Patent; Buettelmann, Bernd; Knust, Henner; Thomas, Andrew William; US2006/128691; (2006); A1;,
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Synthetic Route of 64115-88-4,Some common heterocyclic compound, 64115-88-4, name is 1-Bromo-2-(trifluoromethoxy)benzene, molecular formula is C7H4BrF3O, 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.

Step 1: tert-butyl 1-(2-(trifluoromethoxy)phenyl)piperidin-4-ylcarbamate A mixture of 1-bromo-2-(trifluoromethoxy)benzene (2.40 g, 9.96 mmol), tert-butyl N-(4-piperidyl)carbamate (1.99 g, 9.96 mmol), Pd2(dba)3 (546 mg, 597 umol), BINAP (744 mg, 1.20 mmol), t-BuONa (6.47 g, 69 mmol) in toluene (50 mL) was stirred at 90 C. for 16 h. Cooled to rt, filtered and concentrated, eluted with EtOAc (50 mL), washed with H2O (100 mL), then extracted with EtOAc (100 mL*3), washed with brine (50 mL*2), dried, concentrated to afford methyl 5-formyl-2,4-dimethylbenzoate (1.6 g, 32.6%) as brown gum. ESI-MS (EI+, m/z): 361 [M+H]+.

The synthetic route of 64115-88-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Navitor Pharmaceuticals, Inc.; O’Neill, David John; Saiah, Eddine; Kang, Seong Woo Anthony; Brearley, Andrew; Bentley, Jonathan; (519 pag.)US2018/127370; (2018); A1;,
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Application of 33311-29-4, A common heterocyclic compound, 33311-29-4, name is 4-(2-Methoxyethoxy)aniline, molecular formula is C9H13NO2, 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.

tert-Butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (800 mg, 2.37 mmoL) and 4-(2-methoxyethoxy)aniline (576 mg, 2.84 mmoL) were suspended in tert-amyl alcohol (14 mL) and acetic acid (5 drops). Heated to reflux for 4 h. After cooling, solvent was removed via rotary evaporation. The dark oil was partitioned between water/brine and THF (10 mL each), agitated, and separated layers and dried organic phase over sodium sulfate. The solvent was removed via rotary evaporation to afford a purple solid, 0.55 g. LC/MS (RT=2.997/(M+1)) 470.2. Additional 150 mg of product minus the (BOC) protecting group crystallized from the aqueous layer

The synthetic route of 33311-29-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Celgene Avilomics Research, Inc.; Tester, Richland; Chaturvedi, Prasoon; Zhu, Zhendong; Surapaneni, Sekhar S.; Beebe, Lisa; US2015/174128; (2015); A1;,
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Application of 1663-61-2,Some common heterocyclic compound, 1663-61-2, name is (Triethoxymethyl)benzene, molecular formula is C13H20O3, 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.

Step-1: To a stirred solution of methyl 2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-6-carboxylate (0.18 g, 0.9366 mmol) in acetic anhydride (4 ml) was added triethyl orthobenzoate (0.630 g, 2.8098 mmol) at RT and the mixture was refluxed for 3 h at 110° C. The reaction mixture was evaporated and the resulting residue was used as such into next step without purification. [0212] Step-2: To a stirred solution of product from step-1 (0.18 g) in DMF (4 ml) was added N-(4-aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide (0.180 g, 0.6861 mmol) at RT and the reaction mixture was heated at 110° C. for 1 h. The reaction mixture was cooled to RT and stirred with triethyl amine (1 ml) for half an hour. The reaction mixture was evaporated and the crude product was purified by column chromatography using 0 to 10percent methanol in dichloromethane as eluent to afford (Z)-methyl 1-acetyl-3-((4-(N-methyl-2-(4-methylpiperazin-1-yl) acetamido)phenylamino)(phenyl)methylene)-2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-6-carboxylate as yellow solid. MS (ES+): m/z 583.4 (MH+).

The synthetic route of 1663-61-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ANGION BIOMEDICA CORP.; NARAYAN, Prakash; HUANG, Brian; PAKA, Prani; PAKA, Latha; GOLDBERG, Itzhak D.; US2015/105380; (2015); A1;,
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Application of 175278-17-8, 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. 175278-17-8 name is 2-Bromo-4-(trifluoromethoxy)aniline, 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 solution of commercially available 2-bromo-4-(trifluoromethoxy)aniline (theproduct of step 1, Example 55, 4.00 g, 15.63 mmol) in DMF (1 0 mL) was addedslowly to a suspension of NaH (60% in mineral oil, 1.13 g, 46.88 mmol) in DMF(20 mL) at 0C. After warming to room temperature the reaction mixture wasstirred for 30 minutes. Commercially available tert-butyl 4-(chloromethyl)-5,6-dihydropyridine-1 (2H)-carboxylate (3.62 g, 15.63 mmol) in DMF (1 0 mL) was added and the mixture stirred at room temperature for 1 hour. Cold water (100 mL) was added and the mixture extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with cold water (2 x 50 mL) and brine(5OmL), dried over anhydrous sodium sulphate and concentrated. The crudematerial was purified by flash chromatography eluting with 20% ethylacetate/hexane to afford the title compound as grey solid (2.5 g, 36%): 1 H NMR(400 MHz, DMSO-d6) oe: 1 .38 (5, 9 H), 1 .99 (bs, 2 H), 3.39 (t, 2 H), 3.75 (bs, 4 H),5.50 (5, 1 H), 5.79 (t, 1 H), 6.60 (d, 1 H), 7.17 (d, 1 H), 7.47 (d, 1 H). LC-Ms(m/z): [M-H] = 448.8.

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

Reference:
Patent; ZOETIS SERVICES LLC; WENDT, John; COX, Mark; SHEEHAN, Susan, M.k.; CURTIS, Michael, P.; RESPONDEK, Tomasz; EWIN, Richard, Andrew; KYNE, Graham, M.; JOHNSON, Paul, D.; WO2015/100232; (2015); A2;,
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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. 36449-75-9, name is 1-(2-Bromoethyl)-2-methoxybenzene, A new synthetic method of this compound is introduced below., Recommanded Product: 1-(2-Bromoethyl)-2-methoxybenzene

Compound 1. 1 -(2-methoxyphenethyl)-4-phenethylpiperidine A 250 mL round bottom flask was equipped with a magnetic stir bar, and then charged with 5 grams (0.0537 mol) of 4-picoline, 6.84 grams (0.0644 mol) of benzaldehyde, and 50 mL of acetic anhydride. The reaction mass was heated to reflux and maintained at that temperature for 72 hours. The reaction mixture was then cooled to room temperature, and subjected to silica chromatography. Yield of (E)-4-styrylpyridine was 5.2 grams (53%). The 5.2 grams of (E)-4-styrylpyridine was then charged into a 500 ml hydrogenation flask, to which was added 50 mL of acetic acid as well as 43 mg of Pt02. The reaction mass was subjected to 45 psi of hydrogen gas, and allowed to react at room temperature for 16 hours. The reaction mixture was then filtered through a pad of celite, evaporated, basified with aqueous Na2C03 solution, and extracted with dichloromethane. The combined extraction solvents were removed under reduced pressure via rotovap. The residue was then subjected to silica chromatography, yielding 4.6 grams (78.4% yield) of 4-phenethylpiperidine. A 100 mL round bottomed flask equipped with a magnetic stir bar was then charged with 2.0 grams of 4-phenethylpiperidine (0.0106 mol), 2.5 grams of 2-methoxyphenethylbromide (0.0127 mol), 3.65 grams of K2C03 (0.0264 mol), and 25 mL of DMF as solvent. The reaction mass was then heated to 70 C for 24 hours. The excess DMF was removed via reduced pressure, partitioned with water and dichloromethane, the organic layer separated; excess solvent removed under reduced pressure and the residue was subjected to silica chromatography. Yield of 1 -(2-methoxyphenethyl)-4-phenethylpiperidine was 2.14 grams (62.3% yield). NMR (300 MHz, CDC13) delta 1.31 -1.63 (m, 7H), 2.32-2.85 (m, 10H), 3.87 (s, 3H), 6.83-7.35 (m, 9H) ppm.

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; UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION; CROOKS, Peter, A.; DWOSKIN, Linda, P.; CULVER, John; NICKELL, Justin, R.; ZHENG, Guangrong; WO2014/144064; (2014); A2;,
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Synthetic Route of 89521-55-1, 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 89521-55-1 as follows.

EXAMPLE 27; Ethyl[8-(benzyloxy)-3-oxo-3,4-dihydroquinoxaline-2(1H)-ylidene]acetate 60a; To 3-(benzyloxy)benzene-1,2-diamine (300 mg, 1.4 mmol) in solution in 2 ml of acetic acid, add diethyloxalacetate sodium salt (295 mg, 1.4 mmol) and stir under reflux for 2 hours. Evaporate to dryness and chromatograph to obtain the abovenamed product. Yield: 20%. 1H-NMR (200 MHz, DMSO-d6): delta 11.39 (broad s, 1H, NH), 8.70 (broad s, 1H, NH), 7.53-7.37 (m, 5H arom.), 6.93-6.84 (t, 1H, J=8 Hz, 1H arom.), 6.71-6.67 (d, 1H, J=8 Hz, 1H arom.), 6.57-6.53 (d, 1H, J=8 Hz, 1H arom.), 5.84 (s, 1H, CCH), 5.29 (s, 1H, OCH2-Ph), 4.30-4.20 (q, 2H, J=7 Hz, OCH2-CH3), 1.35-1.28 (t, 3H, J=7 Hz, OCH2CH3).

According to the analysis of related databases, 89521-55-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Schmitt, Martine; Klotz, Evelyne; Macher, Jean-Paul; Bourguignon, Jean-Jacques; Abarghaz, Mustapha; Wagner, Patrick; Ronsin, Gael; US2006/183909; (2006); A1;,
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