Tag: M.W=100-200

Electric Literature of 651734-54-2, A common heterocyclic compound, 651734-54-2, name is 2,6-Difluoro-3,5-dimethoxyaniline, molecular formula is C8H9F2NO2, 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.

To a 2-L reactor equipped with a thermocouple, a nitrogen inlet and mechanical stirrer were charged AOV-dimethyl formamide (450 mL, 425 g), 4-chloro-2-(morpholinomethyl)-l- (phenylsulfonyl)- 1 //-pyrrolo|2.3-6 |pyridine-5-carbaldehyde (30.0 g, 71.45 mmol) and 2,6- difluoro-3,5-dimethoxyanihne (14.2 g, 75.0 mmol). To this suspension (internal temperature 20 C) was added chlorotrimethylsilane (19.4 g, 22. 7 mL, 179 mmol) dropwise in 10 min at room temperature (internal temperature 20-23 C). The suspension changed into a solution in 5 min after the chlorotrimethylsilane addition. The solution was stirred at room temperature for 1.5 h before cooled to 0-5 C with ice-bath. Borane-THF complex in THF (1.0 M, 71.4 mL, 71.4 mmol, 64.2 g, 1.0 eq.) was added dropwise via additional funnel over 30 min while maintaining temperature at 0-5 C. After addition, the mixture was stirred for 4 h. Water (150 g, 150 mL) was added under ice-bath cooling in 20 min, followed by slow addition of ammonium hydroxide solution (28% N, 15.3 g, 17 ml, 252 mmol, 3.53 eq.) to pH 9-10 while maintaining the temperature below 10 C. More water (250 mL, 250 g) was added through the additional funnel. The slurry was stirred for 30 min and the solids were collected by filtration. The wet cake was washed with water (90 g x 2, 90 ml x 2) and heptane (61.6 g x2, 90 ml x 2). The product w as suction dried overnight to give the desired product LG-((4- chloro-2-(morphohnomethyl)-l-(phenylsulfonyl)-li/-pyrrolo[2,3-Z>]pyridin-5-yl)methyl)-2,6- difluoro-3,5-dimethoxyaniline (41.6 g, 96% yield): LCMS calculated for C27H28ClF2N405S[M+H]+: 593.10; Found: 593.1 ; NMR (400 MHz, DMSO-d6) 5 8.36 (m, 2H), 8.28 (s, 1H), 7.72 (m, 1H), 7.63 (m, 2H), 6.78 (s, 1H), 6.29 (m, 1H), 5.82 (m, 1H), 4.58 (m, 2H), 3.91 (s, 2H), 3.76 (s, 6H), 3.56 (m, 4H), 2.47 (m, 4H).

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; INCYTE CORPORATION; BURN, Timothy C.; LIU, Phillip C.; FRIETZE, William; JIA, Zhongjiang; TAO, Ming; WANG, Dengjin; ZHOU, Jiacheng; LI, Qun; (262 pag.)WO2019/213544; (2019); A2;,
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These common heterocyclic compound, 89282-70-2, name is 2-Methoxy-2-methylpropan-1-amine, 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. HPLC of Formula: C5H13NO

The following Examples were prepared according to Method 5 (Example 54) above using 8-chloro-A/-(2-methoxy-4-(1 -methyl-1 H-pyrazol-4-yl)phenyl)pyrido[3,4- d]pyrimidin-2-amine (Example 94) and the appropriate amine as described. Where the amine hydrochloride was used, triethylamine (190uL, 0.373 mmol) was also added to the reaction. The crude reaction residues were purified as above or according to one of the following methods: Method A: Silica gel column chromatography eluting with 0-5% or 0-10% MeOH in DCM. Method B: Silica gel column chromatography eluting with 0-5% MeOH in EtOAc. Method C: Silica gel column chromatography eluting with 0-70% EtOAc in cyclohexane followed by reverse phase preparative HPLC eluting with 10-90% MeOH in water (0.1% formic acid).

The synthetic route of 2-Methoxy-2-methylpropan-1-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; HOELDER, Swen; BLAGG, Julian; SOLANKI, Savade; WOODWARD, Hannah; NAUD, Sebastian; BAVETSIAS, Vassilios; SHELDRAKE, Peter; INNOCENTI, Paolo; CHEUNG, Jack; ATRASH, Butrus; WO2014/37750; (2014); A1;,
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Adding a certain compound to certain chemical reactions, such as: 7252-83-7, name is 2-Bromo-1,1-dimethoxyethane, 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 7252-83-7, Application In Synthesis of 2-Bromo-1,1-dimethoxyethane

Dimethyl malonate (3.70 mL, 32.4 mmol) was added dropwise to a stirred solution of NaH(780 mg, 32.4 mmol) in DMF (50 mL) at 0 C, and the resultant mixture was stirred at 0 Cfor 1 h. KI (980 mg, 6.00 mmol) and 2-bromo-1,1-dimethoxyethane (3.50 mL, 29.6 mmol)were added and the resultant mixture was allowed to warm to rt, then heated at 100 C for24 h. Saturated aq NH4Cl (30 mL) was added and the resultant mixture was extracted withCH2Cl2 (4 × 70 mL). The combined organic extracts were dried over MgSO4, thenconcentrated in vacuo. Purification via flash column chromatography (petrol/Et2O, 2:1) gavethe title compound as a colourless oil (4.62 g, 72%), with spectroscopic data in accordancewith the literature.

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:
Article; Robinson, Emily R. T.; Frost, Aileen B.; Elias-Rodriguez, Pilar; Smith, Andrew D.; Synthesis; vol. 49; 2; (2017); p. 409 – 423;,
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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. 6443-69-2, name is 1,2,3-Trimethoxy-5-methylbenzene, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C10H14O3

REFERENCE EXAMPLE 5 To a solution (50 ml) of 18-acetoxy-n-octadecanoyl chloride (11 g) in 1,2-dichloroethane is added aluminum chloride (7 g), and the mixture is stirred at room temperature for 2 hours. The reaction mixture is cooled to 5 C., followed by addition of a solution (20 ml) of 3,4,5-trimethoxytoluene (6.2 g) in 1,2-dichloroethane. The whole mixture is stirred at room temperature for 72 hours. Further, the reaction mixture is heated to 50-60 C. and stirred for 30 minutes. After cooling, ice water is added and the product is extracted with dichloromethane. The dichloromethane layer is washed with water and the solvent is distilled off to give an oil (12.1 g). The oil is dissolved in methanol (150 ml) followed by addition of sodium hydroxide (5.2 g) and stirring at room temperature for 2 hours. The reaction mixture is neutralized with 5 N hydrochloric acid and the solvent is distilled off to give crude crystals. Washing the product with water and recrystallization from dichloromethane-ether (1:1) give colorless needles of 6-(18-hydroxy-1-oxooctadecyl)-2,3-dimethoxy-5-methylphenol (6.4 g). m.p. 101 C.

According to the analysis of related databases, 6443-69-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Takeda Chemical Industries, Ltd.; US4436753; (1984); A;,
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Related Products of 20781-20-8, 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. 20781-20-8 name is (2,4-Dimethoxyphenyl)methanamine, 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.

To a solution of compound 58 (6.6 g, 33.5 mmol) in dichloromethane (100 mE) were added DIPEA (8.65 g, 67 mmol), HOSt (5.4 g, 36.85 mmol) and EDCI (9.6 g, 50.3 mmol). Afier about 15 mm stirring, to the homogeneous reaction mixture was added a solution of 2,4-dimethoxy- benzyl amine (5.6 g, 33.5 mmol) in dichloromethane (50 mE) dropwise under nitrogen atmosphere. The resulting mixture was stirred under nitrogen atmosphere at room temperature for 16 h. The reaction mixture was washed successively with iN NaOH (100 mE), water (100 mE) and brine (100 mE). The organic phase was then dried over Na2SO4 and evaporated to give a crude solid product 59 that crystallized from ethyl ether. Filtration and open air suction drying afforded an off-white solid pure product 9.8 g (96%), (MS: [M+1]=347).

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

Reference:
Patent; AgeneBio, Inc.; Mekonnen, Belew; Butera, John A.; Huang, Jianxing; (331 pag.)US2018/170941; (2018); A1;,
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6346-09-4, name is 4,4-Diethoxybutan-1-amine, 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. Recommanded Product: 6346-09-4

Triethylamine (25.6 mL, 185 mmol, 2 eq.) at 0 C was added to a solution of 4-aminobutyraldehyde diethyl acetal (15.0 g, 92.2 mmol, 1.0 eq.) in anhydrous dichloromethane (150 mL) under nitrogen atmosphere, and the reaction mixture was allowed to stir for 15 min, followed by dropwise addition of acetic anhydride (43.9 mL, 464 mmol, 5.0 eq.) at 0 C. The resulting reaction mixture was stirred for 2 h at 40 C. The resulting reaction mixture was quenched with a saturated aqueous solution of Na2CO3 (500 mL) and extracted with dichloromethane (100 mL × 4). The combined organic extract was dried over anhydrous Na2SO4 and concentrated under reduced pressure, yielding the desired compound B, (Fig. 1A, 15.5 g, 82% yield) as colorless oil. The compound was used as such in the next step without further characterization and confirmation.

The synthetic route of 6346-09-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Boutin, Jean A.; Bouillaud, Frederic; Janda, Elzbieta; Gacsalyi, Istvan; Guillaumet, Gerald; Hirsch, Etienne C.; Kane, Daniel A.; Nepveu, Francoise; Reybier, Karine; Dupuis, Philippe; Bertrand, Marc; Chhour, Monivan; Le Diguarher, Thierry; Antoine, Mathias; Brebner, Karen; Da Costa, Herve; Ducrot, Pierre; Giganti, Adeline; Goswami, Vishalgiri; Guedouari, Hala; Michel, Patrick P.; Patel, Aakash; Paysant, Jerome; Stojko, Johann; Viaud-Massuard, Marie-Claude; Ferry, Gilles; Molecular Pharmacology; vol. 95; 3; (2019); p. 269 – 285;,
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Reference of 51344-14-0, A common heterocyclic compound, 51344-14-0, name is N,N-Dimethyl-2-(p-tolyloxy)ethanamine, molecular formula is C11H17NO, 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.

To a test tube containing a magnetic bar was added aryl halide (1.0 mmol), Cu2O (14.3 mg, 0.1 mmol), KOH (169 mg, 3.0 mmol), 2-dimethylaminoethanol (0.3 mL, 3.0 mmol), and DMSO/H2O (1.5 mL/0.5 mL). After flushing with argon, the mixture was stirred in a preheated oil bath at 100 C for 24 h. After cooled to ambient temperature, the reaction mixture was distributed in aqueous HCl (5 %) and ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous MgSO4, and concentrated under vacuum. The crude product was further purified by column chromatography (EtOAc/n-Hexane) to provide the phenols.

The synthetic route of 51344-14-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Kim, Jihye; Battsengel, Oyunsaikhan; Liu, Yajun; Chae, Junghyun; Bulletin of the Korean Chemical Society; vol. 36; 12; (2015); p. 2833 – 2840;,
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Synthetic Route of 61367-43-9, 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. 61367-43-9, name is cis-4-Methoxycyclohexanamine hydrochloride belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 284 6-(4-(4-cyano-2-fluorophenyl)-5-hydroxy-lH-pyrazol-l-yl)-N- ((ls,4s)-4-methoxycyclohexyl)nicotinamide [01159] [01160] Combined EDC (1 15 mg, 0.601 mmol), HOBT (27.1 mg, 0.200 mmol), (cis)-4- methoxycyclohexanamine hydrochloride (66.4 mg, 0.401 mmol) and 6-(4-(4-cyano-2- fluorophenyl)-5 -hydroxy- lH-pyrazol-l-yl)nicotinic acid (65 mg, 0.200 mmol) in DMF (0.8 mL) and then added DIPEA (0.175 mL, 1.002 mmol). After 24 hours, the reaction mixture was purified by preparative HPLC (ACN/water with formic acid) to give the title compound (23 mg, 0.053 mmol, 26.3 %) as a tan solid. MS: 436 (M+H). NMR (400 MHz, DMSO- de) 5 ppm 1.34 – 1.48 (m, 2 H) 1.49 – 1.65 (m, 4 H) 1.76 – 1.88 (m, 2 H) 3.17 (s, 3 H) 3.31 (br. s., 1 H) 3.73 – 3.87 (m, 1 H) 7.62 (dd, J=8.2, 1.6 Hz, 1 H) 7.77 (dd, J=1 1.7, 1.6 Hz, 1 H) 8.16 (d, J=3.0 Hz, 1 H) 8.31 – 8.44 (m, 3 H) 8.55 (t, J=8.0 Hz, 1 H) 8.84 (dd, J=2.0, 1.0 Hz, 1 H) 13.71 (br. s., 1 H).

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

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; BROWN, Jason, W.; DAVIS, Melinda; IVETAC, Anthony; JONES, Benjamin; KIRYANOV, Andre, A.; KUEHLER, Jon; LANIER, Marion; MIURA, Joanne; MURPHY, Sean; WANG, Xiaolun; WO2014/160810; (2014); A1;,
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Reference of 768-70-7, A common heterocyclic compound, 768-70-7, name is 3-Ethynylanisole, molecular formula is C9H8O, 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: General produce: o-iodophenol (0.5 mmol), alkyne (1.0 mmol) andbase (1.0 mmol) were added into a 10 mL dry Schlenk tube under Ar,then anhydrous DMF (5 mL) was injected into the mixture using syringe.Then the solution stirred at preheated oil bath (160 C). The reactionwas monitored by TLC and GC.The mixture was cooled down toroom temperature after full conversion, then diluted with dichloromethaneand washed with water three times. The organic layerwas separated and washed with brine followed by drying with anhydrousNa2SO4. The filtrate was concentrated in vacuo to afford thecrude product, which was purified by flash column chromatography onsilica gel (petroleum ether).

The synthetic route of 768-70-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Ji, Guijie; Duan, Yanan; Zhang, Shaochun; Yang, Yong; Catalysis Today; (2019); p. 101 – 108;,
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Electric Literature of 16452-01-0, 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. 16452-01-0, name is 3-Methoxy-4-methylaniline, This compound has unique chemical properties. The synthetic route is as follows.

Step 1 : 6-Methyl-7-methoxy-quinolineglycerol(2.5 eq) FeSO4«7H2O( 0.03 eq)[0182] Using a minimal amount of dioxane, 3-methoxy-4-methylaniline (5.00 g, 36.5 mmol) was slowly added to a mixture of sodium m-nitrobenzenesulfonate (6.62 g, 29.4 mmol), MsOH (20 mL), and FeSO4*7H2O (0.39 g, 1.4 mmol) in a 10OmL round bottom flask heated to an internal temperature of 145-155 0C. Glycerol( 10.75 g, 116.8 mmol) was then added dropwise via addition funnel while keeping the internal temperature at 145-155C. After addition, the reaction was stirred in a 150 0C oil bath until LCMS indicated completion (4-6 h). After being cooled to rt, ice (2Og) was added, then the solution was neutralized with IO N NaOH (calculated to same eq of MsOH) at a speed to keep the internal temperature below 40 0C. A thick suspension appeared after addition, and this was extracted with EtOAc (50 mL x 3). The organic layer was filtered through a Celite pad to remove insoluble black particles and then purified by flash column chromatography on silica gel to give the desired product (5.0 g, 79%). MS (ES) mlz 174.1 (M+ H+).

The chemical industry reduces the impact on the environment during synthesis 3-Methoxy-4-methylaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; CHEMOCENTRYX, INC.; CHEN, Xi; FAN, Pinchen; GLEASON, Mark, M.; JAEN, Juan, C.; LI, Lianfa; MCMAHON, Jeffrey, P.; POWERS, Jay; ZENG, Yibin; ZHANG, Penglie; WO2010/54006; (2010); A1;,
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