Month: May 2021

Synthetic Route of 366-99-4,Some common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, molecular formula is C7H8FNO, 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.

Example 62; Synthesis of N,N’-dicyclopropyl-N-(3-fluoro-4-methoxy-phenyl)-1,3,5-triazine-2,4,6-triamine (157); To cyanuric chloride (0.368 g, 2 mmol) in CH3CN at about -20° C. was added 3-fluoro-p-anisidine (0.28 g, 2 mmol) in CH3CN followed by the addition of DIEA (0.39 mL, 2.2 mmol) and stirred for about I hour. The reaction mixture was then stirred at room temperature for about 1 hour. Then cyclopropylamine (1.39 mL, 20 mmol) and DIEA (0.39 mL, 2.2 mmol) were added and the reaction mixture was stirred overnight at rt. The reaction mixture was worked up as usual, diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over sodium sulfate, filtered, concentrated under reduced pressure, and compound 157 was purified by silica gel column chromatography (200 mg, 30percent), mp 91-92° C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 8.6 min, 99.1percent purity; MS (ESI): m/z 331(M+H, 100), 305 (0.8), 151 (0.3).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Fluoro-4-methoxyaniline, its application will become more common.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krlshna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209880; (2004); A1;,
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Some common heterocyclic compound, 111-95-5, name is Bis(2-methoxyethyl)amine, molecular formula is C6H15NO2, 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. Computed Properties of C6H15NO2

A solution of (S)-isopropyl 2-(6-(bromomethyl)-4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4- fluorophenethoxy)phenyl)-2-methylpyridin-3 -yl)-2-(tert-butoxy)acetate (0.015 g, 0.022 mmol) and bis(2-methoxyethyl)amine (0.02 g, 0.150 mmol) in EtOH (1 mL) was stirred for 2 h. Sodium hydroxide(0.04 g, 1.000 mmol) was added and the reaction mixture wasstirred at 80 C for 2 h. Then, cooled and purified by prep HPLC to afford (S)-2-(6- ((bis(2-methoxyethyl)amino)methyl)-4-(4,4-dimethylpiperidin- 1 -yl)-5-(4-(4- fluorophenethoxy)phenyl)-2-methylpyridin-3 -yl)-2-(tert-butoxy)acetic acid (0.0127 g, 0.0 18 mmol, 83 % yield). LCMS (M+H) = 694.2.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 111-95-5, its application will become more common.

Reference:
Patent; VIIV HEALTHCARE UK (NO.5) LIMITED; EASTMAN, Kyle J.; KADOW, John F.; NAIDU, B. Narasimhulu; PARCELLA, Kyle E.; PATEL, Manoj; SIVAPRAKASAM, Prasanna; TU, Yong; (275 pag.)WO2017/25915; (2017); A1;,
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Related Products of 352-67-0, A common heterocyclic compound, 352-67-0, name is 1-Fluoro-4-(trifluoromethoxy)benzene, molecular formula is C7H4F4O, 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 stirred solution [OF TRANS-4-AMINOCYCLOHEXANOL (230] mg, [2MMOL)] in DMF (10 mL) at 0 C was added 60% NaH in mineral oil (240 mg, 6 mmol). The reaction mixture was stirred at 0 [C] [FOR’/2 HOUR] and then [1-FLUORO-4- (TRIFLUOROMETHOXY)] benzene (432 mg, 2.4 mmol) was added. It was heated to 60 [C] for 2 hours and stirred for 12 hours at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water (3 times) and brine. The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure to provide the titled compound. MS (DCI) [M/Z] 276 (M+H) [+.]

The synthetic route of 352-67-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBOTT LABORATORIES; WO2004/26822; (2004); A2;,
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Related Products of 22236-10-8, The chemical industry reduces the impact on the environment during synthesis 22236-10-8, name is 4-(Difluoromethoxy)aniline, I believe this compound will play a more active role in future production and life.

The reaction is carried out under protective gas (argon). A mixture of 2.39 g (12 mmol) 1-(4-bromophenyl)ethanone, 0.99 mL (8 mmol) 4-(difluoromethoxy)aniline, 2.21 g (16 mmol) potassium carbonate, 150 mg (0.8 mmol) copper iodide and 180 mg (1.6 mmol) L-proline in 12 mL DMSO was stirred for 72 hours at 95 C. The reaction mixture was added to water, mixed with a little ammonia extracted twice with tert-butyl-methylether. The combined organic phases were dried on sodium sulphate and evaporated to dryness in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether+30% ethyl acetate). The product was further reacted directly.Yield: 33% of theoryC15H13F2NO2 (277.27)Rt=1.98 min. method 1

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, 4-(Difluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2010/240669; (2010); A1;,
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Synthetic Route of 1535-75-7, 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. 1535-75-7 name is 2-(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.

General procedure: Acetamides (1a-1x, 1ab, 1ac and 1ba-1bc). To a solution of 2-phenylacetic acid (7.0mmol), 2-(trifluoromethoxy)aniline (7.7mmol) in anhydrous CH2Cl2 (25mL) were added EDCI (1.745g, 9.1mmol) and DMAP (256.6mg, 2.1mmol). The reaction mixture was stirred at room temperature overnight, diluted with HCl (1M) aqueous solution, and extracted with CH2Cl2 (3×25mL). The combined organic phase was washed with saturated NaHCO3 aqueous solution and brine, dried over anhydrous Na2SO4, and concentrated under vacuum. Purification by flash chromatography (Silica gel, petroleum ether: ethyl acetate=50: 1 as eluent) gave the corresponding 2-phenyl-N-[2-(trifluoromethoxy)phenyl]acetamide compound.

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

Reference:
Article; Zhao, Xiao-Jing; Zhao, Jie; Sun, Xin; Liu, Ji-Kai; Wu, Bin; Tetrahedron; vol. 73; 25; (2017); p. 3463 – 3477;,
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Synthetic Route of 4342-46-5, 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 4342-46-5 as follows.

To a mixture of compound G36 (200 mg, 349 umol) and compound G37 (90.19 mg, 698 umol) in toluene (5 mL) were added Pd2(dba)3 (31.9 mg, 34.9 umol), t-BuONa (50.3 mg, 523 umol, 1.5 eq) and BINAP (21.7 mg, 34.9 umol), and the mixture was stirred at 95C for 4 hours to give a yellow mixture. LCMS showed the reaction was not completed. The mixture was stirred at 95C for another 6 hours to give a red mixture. TLC showed the reaction was completed. The mixture was partitioned between EtOAc (15 ml) and water (10 mL). The aqueous phase was extracted with EtOAc (10 mL x 2). The combined organic extract was washed with brine (130 mL), dried over Na2S04, filtered, concentrated under reduced pressure to give crude product. The crude product was purified by combi flash to afford compound G38 (130 mg) as a yellow solid.

According to the analysis of related databases, 4342-46-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; QURIENT CO., LTD.; LEAD DISCOVERY CENTER GMBH; NAM, Kiyean; KIM, Jaeseung; JEON, Yeejin; YU, Donghoon; SEO, Mooyoung; PARK, Dongsik; EICKHOFF, Jan; ZISCHINSKY, Gunther; KOCH, Uwe; (138 pag.)WO2019/197546; (2019); A1;,
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Some common heterocyclic compound, 6346-09-4, name is 4,4-Diethoxybutan-1-amine, molecular formula is C8H19NO2, 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. Product Details of 6346-09-4

Procedure 16: Protection of Amine by Fmoc GroupTo a stirring solution of the amine (0.049 mol) in DCM (100 mL), was added DIPEA (16 mL, 0.099 mol) and the reaction mixture was cooled to 0C. Fmoc- Cl (12.8 g, 0.049 mol) was then added portion-wise over several minutes, and the reaction was allowed to warm to room temperature for 2 hr. The organic layer was washed with water (2 x 50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated to dryness to yield the Fmoc protected amine (90-95% yield). Example 43 6′-(4-Amino-butyl)-l-(4-amino-2(5)-hydroxy-butyryl)-sisomicinN-Fmoc-4-amino-butyraldehyde diethyl acetal4-Amino-butyraldehyde diethyl acetal (8.0 g, 0.050 mol) was Fmoc protected following Procedure 16 to give the desired N-Fmoc-4-amino-butyraldehyde diethyl acetal (22.08 g, MS m/e [M+Na]+ calcd 406.2, found 406.1), which was carried through to the next step without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6346-09-4, its application will become more common.

Reference:
Patent; ACHAOGEN, INC.; WO2009/67692; (2009); A1;,
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Related Products of 4393-09-3, 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. 4393-09-3, name is (2,3-Dimethoxyphenyl)methanamine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of (2,3-dimethoxyphenyl)methanamine (SM-2) (5 g, 29.9 mmol) in THF (50 mL) were added Et3N (8.3 mL, 59.8 mmol) dropwise at 0 C. After stirring for 15 minutes, 2- bromoacetonitrile (2.5 mL, 35.9 mmol) dropwise at 0 C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was stirred at room temperature for 16 h.After consumption of the starting material (by TLC), the reaction was quenched with water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layer was washed with brine, dried over Na2S04and concentrated under reduced pressure. The crude was purified by column chromatography by eluting 20% EtOAc/n-hexane to afford Int-A (5 g, 82%) as colorless thick syrup.1H NMR (400 MHz, DMSO -d6) delta 7.07 – 7.00 (m, 1H), 6.98 – 6.89 (m, 2H), 3.79 (s, 3H), 3.76 – 3.74 (m, 2H), 3.73 (s, 3H), 3.59 (br d, J = 5.9 Hz, 2H), 2.81 (br s, 1H)

The synthetic route of (2,3-Dimethoxyphenyl)methanamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; APTINYX INC.; KHAN, M., Amin; (87 pag.)WO2019/152685; (2019); A1;,
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Adding a certain compound to certain chemical reactions, such as: 70894-71-2, name is N-(4-Methoxybenzyl)cyclopropanamine, 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 70894-71-2, Recommanded Product: 70894-71-2

A solution of ethyl 6,8-dichloroimidazo[l ,2-b]pyridazine-3-carboxylate (4.0 g, 15.38 mmol), N-(4-methoxybenzyl)cyclopropanamine (4.09 g, 23.07 mmol) and diisopropylethyl amine (5.37 mL, 30.8 mmol) in tetrahydrofuran (THF, 5 mL) was refluxed at 70 C overnight. The reaction was concentrated and the crude product was purified using silica gel chromatography (25-30% ethyl acetate: petroleum ether), to provide ethyl 6-chloro-8-(cyclopropyl(4-methoxybenzyl)amino)imidazo[l ,2- b]pyridazine-3-carboxylate (4.3 g, 56% yield). 1H NMR (400 MHz, CHLOROFORM-D) delta ppm 8.14 (1 H, s), 7.05 – 7.07 (1 H, m), 7.02 – 7.05 (1 H, m), 6.76 – 6.79 (1 H, m), 6.74 – 6.76 (1 H, m), 6.60 (1 H, s), 5.61 (2 H, s), 4.43 (2 H, q, J=7.22 Hz), 3.75 (3 H, s), 2.45 – 2.54 (1 H, m), 1.41 (3 H, t, J=7.05 Hz), 0.96 – 1.04 (2 H, m), 0.76 – 0.84 (2 H, m). LC retention time 2.22 min [O]. MS (E+) m/z: 401 (MH+).

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; BRISTOL-MYERS SQUIBB COMPANY; WEINSTEIN, David S.; MOSLIN, Ryan M.; ZHANG, Yanlei; GARDNER, Daniel S.; SANTELLA, Joseph B.; LANGEVINE, Charles M.; STACHURA, Sylwia; (127 pag.)WO2017/87590; (2017); A1;,
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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 38336-04-8 as follows. HPLC of Formula: C9H13NO

Example 13; N-[6-(2-Benzyloxy-ethylamino)-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide:; A mixture of 318 mg (1 mmol) of N-(6-fluoro-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide, 605 mg (4.0 mmol) of 2-benzyloxy-ethylamine and 3.2 ml of ethanol is heated at 120C in a closed vial in a microwave reactor for 10 minutes. After cooling to room temperature, 1M aqueous hydrochloric acid is added until a pH value of ~3 is reached. The resulting mixture is extracted with ethyl acetate. The organic phase is separated, washed with water and brine, dried over magnesium sulfate and evaporated. Chromatography of the residue on silica with dichloro-methane – methanol (93:7) and crystallization from tetrahydrofuran – hexane gives 261 mg (58 %) of the title compound as red crystals, m.p. 204C (decomp.).

According to the analysis of related databases, 38336-04-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2006/10591; (2006); A2;,
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