761440-16-8 | Pyrimidines

Sep 2021 News Some tips on 761440-16-8

At the same time, in my other blogs, there are other synthetic methods of this type of compound,761440-16-8, 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine, and friends who are interested can also refer to it.

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine, molecular formula is C13H13Cl2N3O2S, molecular weight is 346.23, as common compound, the synthetic route is as follows.HPLC of Formula: C13H13Cl2N3O2S

2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)py-rimidine-4-amine (472 mg, i.36 mmol) was dissolved in 0.08 M HC1-ethoxyethanol (i .0 mE), to which the compound (200 mg, 0.979 mmol) prepared in preparative example 2i was added, followed by stirring at 80 C. for i2 hours. The reaction mixture was cooled to room temperature, neutralized with sodium hydrogen carbonate aqueous solution, and extracted twice with ethylacetate. The extracted organic layer was dried over sodium sulfate and then filtered. The solvent was eliminated by distillation under reduced pressure. Then, purification was performed by silica gel column chromatography (eluent: methanol dichloromethane, 1/9) to give the target compound 2-(4-((5- chioro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidine- 2-yl)amino)-5-methoxy-2-methylphenyl)-2- methylpropanenitrile as a white solid (433 mg, 0.875 mmol, yield: 86%).10584] ?H-NMR (300 MHz, CDC13) oe 9.53 (s, br, 1H),8.52 (d, J=8.3 Hz, 1H), 8.18 (s, 1H), 8.12 (s, 1H), 7.94 (d,J=7.9 Hz, 1H), 7.66 (t, J=7.3 Hz, 1H), 7.53 (s, br, 1H), 7.28(t, J=7.8 Hz, 1H), 6.83 (s, 1H), 3.90 (s, 3H), 3.26 (sept, J=6.9Hz, 1H), 2.44 (s, 3H), 1.79 (s, 6H), 1.32 (d, J=6.9 Hz, 6H);LC/MS 513.8 [M+H].

Reference:
Patent; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; Kim, Pilho; Kim, Hyoung Rae; Cho, Sung Yun; Ha, Jae Du; Jung, Hee Jung; Yun, Chang Soo; Hwang, Jong Yeon; Park, Chi Hoon; Lee, Chong Ock; Ahn, Sunjoo; Chae, Chong Hak; (97 pag.)US2018/111905; (2018); A1;,
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A new synthetic route of 761440-16-8

According to the analysis of related databases, 761440-16-8, the application of this compound in the production field has become more and more popular.

Related Products of 761440-16-8, Adding some certain compound to certain chemical reactions, such as: 761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine,molecular formula is C13H13Cl2N3O2S, 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 761440-16-8.

Tert-butyl 4- (4-amino-5-isopropoxy-2-methylphenyl) piperidine-(0.300 g, 0.861 mmol),(0.298 g, 0.861 mmol), Pd [P (tBu) 3] 2 (0.044 g, 0.086 mmol) was added to a solution of 2,5-dichloro-N- (2- (isopropylsulfonyl) phenyl) pyrimidin-Mmol) and NaOtBu (0.083 g, 0.861 mmol) were mixed in toluene (5 mL), heated at 150 C for 20 minutes under microwave irradiation, and then cooled to room temperature to complete the reaction. The reaction mixture was poured into water and extracted with ethyl acetateAll. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was purified by column chromatography (SiO2, 12 g cartridge; ethyl acetate / hexane = 0% to 30%) And concentrated to give tert-butyl 4- (4- (5-chloro-4- (2- (isopropylsulfonyl) phenylamino) pyrimidin- -methylphenyl) piperidine-1-carboxylate (0.252 g, 44.5%) as a lemon solid solid.

According to the analysis of related databases, 761440-16-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHONG KUN DANG PHARMACEUTICAL CORP.; YOO, CHUNG-YEOL; JIN, SEOK-MIN; KIM, JU-YOUNG; (34 pag.)KR2016/147358; (2016); A;,
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A new synthetic route of 761440-16-8

According to the analysis of related databases, 761440-16-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHONG KUN DANG PHARMACEUTICAL CORP.; YOO, CHUNG-YEOL; JIN, SEOK-MIN; KIM, JU-YOUNG; (34 pag.)KR2016/147358; (2016); A;,
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Sources of common compounds: 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 761440-16-8, 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine.

Electric Literature of 761440-16-8, 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. 761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine, molecular formula is C13H13Cl2N3O2S, The 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.

Another method for preparing compound 13: Under the protection of nitrogen, compound 2-isopropoxy-5-methyl-4-(2,2,6,6-d4-piperidin-4-yl) aniline dihydrochloride (0.50 g, 1.54 mmol), 2,5- dichloro -N- (2-(isopropylsulfonyl) phenyl) pyrimidin-4-amine (0.58 g, 1.69 mmol) and isopropanol (6 ml) were added into a flask, the reaction was warmed to 85C and conducted overnight, and the reaction was monitored as being substantially completed by HPLC. The reaction mixture was cooled to room temperature, and stirred for 3 hours to precipitate the solid. The mixture was filtered, and the filter cake was beating washed with cold isopropanol to give the desired product hydrochloride. The hydrochloride was dissolved in pure water, an aqueous solution of sodium carbonate was added dropwise slowly to neutralize the pH to 8.5, and then extracted with ethyl acetate for three times. The combined organic phase was dried over anhydrous sodium sulfate, and concentrated to give the desired product as a white solid (0.68g, yield: 78%). MS Calcd.: 561; MS Found: 562 (M+H) +, 584 (M+Na)+. HNMR (DMSO-d6+ D2O, 400 MHz) delta 8.47 (d, J=7.6 Hz, 1H), 8.24 (s, 1H), 7.85-7.83 (dd, J=7.6, 2.0 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.52 (s, 1H), 7.36 (t, J=7.6 Hz, 1H), 6.79 (s, 1H), 4.53-4.50(m, 1H), 3.45-3.38 (m, 1H), 2.94-2.92 (m, 1H), 2.33 (s, 3H), 1.79-1.64 (m, 4H), 1.21 (d, 6H), 1.15 (d, 6H).

Reference:
Patent; Suzhou Zelgen Biopharmaceuticals Co. Ltd.; LV, Binhua; LI, Chengwei; CAO, Benwen; PANG, Xudong; (62 pag.)EP2990405; (2016); A1;,
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Extracurricular laboratory: Synthetic route of 761440-16-8

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, 761440-16-8, 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine.

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. 761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine. This compound has unique chemical properties. The synthetic route is as follows. Computed Properties of C13H13Cl2N3O2S

2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)py-rimidine-4-amine (472 mg, i.36 mmol) was dissolved in0.08 M HC1-ethoxyethanol (i .0 mE), to which the compound (200 mg, i . i3 mmol) prepared in preparative example 20 was added, followed by stirring at 80 C. for i2 hours. The reaction mixture was cooled to room temperature, neutralized with sodium hydrogen carbonate aqueous solution, and extracted twice with ethylacetate. The extracted organic layer was dried over sodium sulfate and then filtered. The solvent was eliminated by distillation under reduced pressure. Then, purification was performed by silica gel colunm chromatography (eluent: methanol/ dichioromethane, i/9) to give the target compound 2-(4-((5- chioro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidine- 2-yl)amino)-5-methoxy-2-methylphenyl)acetonitrile as a white solid (450 mg, 0.926 mmol, yield: 8i%).10581] ?H-NMR (300 MHz, CDC13) oe 9.53 (s, br, iH),8.53 (d, J=8.3 Hz, iH), 8.i8 (s, iH), 8.i3 (s, iH), 7.94 (d, J=7.9 Hz, iH), 7.64 (t, J=8.4 Hz, iH), 7.55 (s, br, iH), 7.28 (t, J=7.8 Hz, iH), 6.86 (s, iH), 3.9i (s, 3H), 3.63 (s, 2H), 3.26 (sept, J=6.9 Hz, iH), 2.i7 (s, 3H), i.3i (d, J=6.9 Hz, 6H); EC/MS 485.9 [M+H].

Some scientific research about 761440-16-8

To a solution of 7 (200 mg, 0.979 mmol) in 0.08 M HCl inethoxyethanol (1.0 mL) and 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine (4, 407 mg, 1.17 mmol) was added at rtand the reaction mixture was stirred at 80 C for 12 h. The solidprecipitated was filtered and washed with ethanol (2 mL). The solidfiltered was then dissolved in EtOAc (50 mL) and washed with sat.NaHCO3 (aq). The combined organic layers were concentrated underreduced pressure to obtain the crude product which was purifiedby silica gel column chromatography using MeOH/DCM (1:9)to afford the title compound (433 mg, 0.875 mmol, 94%) as a whitesolid. Mp 207.4-209.6 C; 1H NMR (300 MHz, CDCl3) delta 9.53 (s, 1H),8.53 (d, J= 8.3 Hz, 1H), 8.18 (s, 1H), 8.12 (s, 1H), 7.94 (dd, J = 7.9,1.3 Hz, 1H), 7.66 (t, J = 7.3 Hz, 1H), 7.53 (s, 1H), 7.30 (t, J = 7.9 Hz, 1H),6.83 (s, 1H), 3.90 (s, 3H), 3.26 (sept, J = 6.9 Hz, 1H), 2.45 (s, 3H), 1.79(s, 6H), 1.32 (d, J = 6.9 Hz, 6H); 13C NMR (125 MHz, CDCl3) delta 157.32,155.40, 155.33, 146.15, 138.34, 134.76, 131.36, 131.11, 128.33, 125.00,124.58, 123.55, 123.38, 122.45, 107.24, 106.48, 55.93, 55.52, 35.00,28.27, 20.78, 15.37; LC/MS m/z 513.8 [M+H+]; HRMS (EI) m/z calcdfor C25H28ClN5O3S [M+] 513.1601, found 513.1607.

Reference:
Article; Mathi, Gangadhar Rao; Kang, Chung Hyo; Lee, Heung Kyoung; Achary, Raghavendra; Lee, Ha-Yeon; Lee, Joo-Youn; Ha, Jae Du; Ahn, Sunjoo; Park, Chi Hoon; Lee, Chong Ock; Hwang, Jong Yeon; Yun, Chang-Soo; Jung, Hee Jung; Cho, Sung Yun; Kim, Hyoung Rae; Kim, Pilho; European Journal of Medicinal Chemistry; vol. 126; (2017); p. 536 – 549;,
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New downstream synthetic route of 761440-16-8

The synthetic route of 761440-16-8 has been constantly updated, and we look forward to future research findings.

Related Products of 761440-16-8 , The common heterocyclic compound, 761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine, molecular formula is C13H13Cl2N3O2S, 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 500L enamel reactor was added 80.6kg of isopropanol,12.4 kg of the compound 1-dihydrochloride obtained in Example 1 and 14.7 kg of the compound 3 obtained in Example 6,Heated to reflux, the reaction 24 hours. The reaction solution was cooled to 10 C, stirred for 3 hours,filter.The wet filtered product was added enamel reactor,99.2 kg of isopropanol and 13.0 kg of purified water were added,Reflux stir until solids are clear.Control temperature not lower than 85 ,99.2 kg of isopropanol was added dropwise.Slowly cooled to 20 ,Stir for 2 hours and filter.The wet filtered product was added to the enamel reactor again,Add 99.2 kg of isopropanol and 13.0 kg of purified water and stir under reflux until the solid is clear.Controlled at a temperature not lower than 85 C, 99.2 kg of isopropanol was added dropwise.Slowly cooled to 20 C, stirred for 2 hours, filtered, washed with isopropanol.The filtered wet product was vacuum dried at 55 C for 16 hours,A 16.4 kg yellow solid (Compound 4, ceritinib dihydrochloride) was obtained in a yield of 67% and a purity of 99.9%.

The synthetic route of 761440-16-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Xingtai Pharmaceutical Technology Co., Ltd.; Liu Xuejun; Hong Huiyi; Chen Xiaodong; (12 pag.)CN106854200; (2017); A;,
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Some scientific research about 761440-16-8

According to the analysis of related databases, 761440-16-8, the application of this compound in the production field has become more and more popular.

Electric Literature of 761440-16-8, The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine. This compound has unique chemical properties. The synthetic route is as follows.

4-(4-Amino-5-isopropoxy-2-methyl-phenyl)-piperidine-l-carboxylic acid tert-butyl ester (170 mg, 0.488 mmol) from the previous step, (2,5-Dichloro-pyrimidin-4-yl)-[2-(propane- 2-sulfonyl)-phenyl]-amine (Intermediate 2, 169 mg, 0.488 mmol, 1 equiv.), xantphos (28 mg, 0.049 mmol, 0.1 equiv.), palladium acetate (5.5 mg, 0.024 mmol, 0.05 equiv.), and Cs2CO3 (477 mg, 1.46 mmol, 3 equiv.) are dissolved in anhydrous THF (6 mL). N2 is bubbled through the reaction mixture for 5 minutes and then the reaction vessel is sealed and heated with microwave irradiation to 150 0C for 20 min. The reaction is filtered and the filtrate concentrated under vacuum. After concentration, the crude product is purified by silica gel chromatography (gradient from hexanes to 30% ethyl acetate in hexanes) to give 4-(4-{5-chloro-4-[2-(propane-2- sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-methyl-phenyl)-piperidine-l- carboxylic acid tert-butyl ester as a yellow film: ESMS m/z 658.3 (M + H+). This product (105 mg, 0.160 mmol) is dissolved in CH2Cl2 (3 mL) and treated with TFA (3 mL). After 45 min., the reaction is concentrated under vacuum. 1 N HCl in Et2O (5 mL x 2) is added causing the product HCl salt to precipitate. The solvent is removed by decantation. The resulting 5- Chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4-[2-(propane-2-sulfonyl)- phenyl]-pyrimidine-2,4-diamine (66) is dried under high vacuum, generating an off-white powder: 1H NMR (400 MHz, DMSO-J6 + trace D2O) delta 8.32 (s, IH), 8.27 (d, IH), 7.88 (d, IH), 7.67 (dd, IH), 7.45 (dd, IH), 7.42 (s, IH), 6.79 (s, IH), 4.56-4.48 (m, IH), 3.49-3.32 (m, 3H), 3.10-2.91 (m, 3H), 2.09 (s, 3H), 1.89-1.77 (m, 4H), 1.22 (d, 6H), 1.13 (d, 6H); ESMS m/z 558.1 (M + H+).

According to the analysis of related databases, 761440-16-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; IRM LLC; WO2008/73687; (2008); A2;,
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Simple exploration of Safety of 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine

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. 761440-16-8, name is 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine. A new synthetic method of this compound is introduced below., Safety of 2,5-Dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine

Isopropanol (445 kg) was added to 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine (70.2 kg, 203 mol, 1.15 eq.) and 2-Isopropoxy-5-methyl-4-(piperidin-4-yl)aniline dihydrochloride (56.7 kg, 176 mol). The mixture was heated for approx. 16 hours at reflux. Water (47 kg) was added and the mixture cooled to 0 C. The solid was filtered and washed with isopropanol/water. To the wet product, isopropanol (680 kg) and water (55 kg) was added and the slurry heated to reflux. The obtained clear solution was cooled to 0 C., filtered and dried under vacuum to yield 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine dihydrochloride (=ceritinib dihydrochloride; 84.5 kg [t.q., contains 10% w/w isopropanol], 76.0 kg [100%], 68% yield). Ethanol (155 kg) and water (113 kg) were added to 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-dihydrochloride; 45.0 kg [t.q., contains 10% w/w isopropanol], 40.5 kg [100%], 64.2 mol) and the mixture heated to 55 C. Aqueous NaOH (147 L of a 1 M solution, 2.3 eq.) was added slowly and then cooled to 20 C. After filtration, the product was recrystallized from ethanol and dried under vacuum to yield ceritinib (33.2 kg, 93% yield based on ceritinib dihydrochloride) as an almost white powder. 1H-NMR (400 MHz, CDCl3): delta=1.33 (d, J=6.8 Hz, 6H), 1.38 (d, J=6.1 Hz, 6H), 1.59-1-78 (m, 5H), 2.18 (s, 3H), 2.75-2.83 (m, 3H), 3.20-3.24 (m, 2H), overlaps 3.28 (sept, J=6.8 Hz, 1H), 4.56 (sept, J=6.1 Hz, 1H), 6.82 (s, 1H), 7.25-7.29 (m, 1H), 7.56 (br. s, 1H), 7.64 (m, 1H), 7.94 (m, 1H), 8.01 (br. s, 1H), 8.16 (br. s, 1H), 8.60 (m, 1H), 9.51 (br. s, 1H) ppm. 13C-NMR (100 MHz, CDCl3): delta=15.4, 18.9, 22.3, 33.9, 38.6, 47.5, 55.4, 71.4, 105.7, 111.0, 120.6, 123.1, 123.7, 124.9, 126.7, 127.3, 131.2, 134.7, 138.3, 138.5, 144.7, 155.3, 155.4, 157.5 ppm, Elemental analysis: calculated (%) for C28H36ClN5O3S: C 60.26, H 6.50, N 12.55, O 8.60 Cl 6.35, S 5.74, found: C 60.15, H 6.45, N 12.72, O 8.58, Cl 6.43, S 5.67.)

Reference:
Patent; Novartis AG; Davis, Mark Clinton; Gong, Baoqing; Har, Denis; Kapferer, Tobias; Zheng, Xuchun; (25 pag.)US2020/39935; (2020); A1;,
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