Month: June 2021

Adding a certain compound to certain chemical reactions, such as: 69843-13-6, name is 1-Methyl-1H-pyrazol-4-amine, belongs to pyrazoles-derivatives 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 69843-13-6, Product Details of 69843-13-6

Step 4: Preparation of tert-butyl {3-[(5-cyano-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]cyclobutyl}carbamate To a microwave reaction vial was added tert-butyl {3-[(2-chloro-5-cyano-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]cyclobutyl}carbamate (508 mg, 1.0 mmol), 1-methyl-1H-pyrazol-4-amine (110 mg, 1.1 mmol), 1,4-dioxane (10 mL), Cs2CO3 (670 mg, 2.1 mmol, 2 mol eq), Xantphos (62 mg, 0.1 mmol) and Pd2(dba)3 (94 mg, 0.1 mmol). The reaction vial was flushed with nitrogen, capped, stirred and heated to 140 C. in a Biotage microwave reactor for 1 hr and 45 min. The reaction was diluted with EtOAc (120 mL) and water (20 mL). The organic layer was separated, washed with water (20 mL), brine (10 mL), and dried over Na2SO4. After concentrating the extract to dryness, the product was purified via flash chromatography eluting with a gradient of 0%-60% EtOAc in heptanes to afford the title compound (480 mg, 84 yield) as a light yellow solid. 1:1 cis:trans mixture: 1H NMR (400 MHz, DMSO-d6) delta ppm 9.42 (s, 1H) 8.11 (s, 1H) 7.96 (br. s., 1H) 7.49-7.60 (m, 1H) 7.20-7.46 (m, 1H) 5.53 (br. s., 2H) 4.11-5.13 (m, 1H) 3.82 (s, 3H) 3.56 (t, J=7.55 Hz, 2H) 2.83 (d, J=6.80 Hz, 1H) 2.39-2.48 (m, 2H) 2.02-2.16 (m, 1H) 1.39 (d, J=5.54 Hz, 9H) 0.84 (t, J=8.06 Hz, 2H) -0.12 (br. s., 9H). m/z (APCI+) for C26H38N8O4Si 555.1 (M+H)+.

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, 1-Methyl-1H-pyrazol-4-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PFIZER INC.; Cheng, Hengmiao; Johnson, JR., Theodore Otto; Kath, John Charles; Liu, Kevin Kun-Chin; Lunney, Elizabeth Ann; Nagata, Asako; Nair, Sajiv Krishnan; Planken, Simon Paul; Sutton, Scott Channing; US2013/79324; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 114474-28-1, 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. 114474-28-1 name is 4-(1H-Pyrazol-4-yl)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.

[0255] A mixture of 2,4-dichloropyrido[3,4-d]pyrimidine (250 mg, 1.25 mmol), 4-(lH- pyrazol-4-yl)aniline (199, 1.25 mmol), and iPr2NEt (0.44 mL, 2.50 mmol) in DMF (2.5 mL) was heated at 100 C for 5h, cooled to rt, and diluted with water. The precipitate formed was collected by filtration and washed with water and dried in vacuo to provide the title compound (400 mg, 99%). MS (ES+) m/e 323 (M+H) +.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(1H-Pyrazol-4-yl)aniline, and friends who are interested can also refer to it.

Reference:
Patent; KADMON CORPORATION, LLC; OLSZEWSKI, Kellen; KIM, Ji-In; POYUROVSKY, Masha; LIU, Kevin; BARSOTTI, Anthony; MORRIS, Koi; (344 pag.)WO2016/210330; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

179692-08-1, name is Ethyl 4-iodo-1H-pyrazole-5-carboxylate, belongs to pyrazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Product Details of 179692-08-1

Example 15, Step C [00154] To a solution of compound 15c (38 g, 143 mmol) in acetonitrile (380 mL) at r.t. was added K2C03 (39.5 g, 286 mmol) and then PMBCI (24 mL, 177 mmol). The reaction mixture was stirred at 60C overnight. After cooling to r.t., the mixture was filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to afford compound 15d (32 g, 58%).[00155] This compound was characterized by proton NMR (1HNMR) and mass spectroscopy (MS) in accordance with the procedures described herein. Proton NMR yielded the following results: 1H NMR (DMSO-d6, 400MHz): delta 8.13(s, 1 H), 7.23(d, J = 8.8 Hz, 2H), 6.90(d, J = 8.8 Hz, 2H), 5.29(s, 2H), 4.24 (q, J = 6.8 Hz, 2H), 3.71 (s, 3H); 1.26(t, J = 6.8 Hz, 3H). Mass spectroscopy indicated MS (ESI): m/z 387 (M+H)+.

The synthetic route of 179692-08-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; ADDEX PHARMA SA; LIVERTON, Nigel, J.; BOLEA, Christelle; CELANIRE, Sylvain; LUO, Yunfu; WO2012/6760; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 37622-90-5, 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. 37622-90-5 name is Ethyl 4-pyrazolecarboxylate, 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.

Intermediate 8 -(4-Chloromethyl-benzyl)-1 H-pyrazole-4-carboxylic acid ethyl ester 1 H-Pyrazole-4-carboxylic acid ethyl ester (2 g, 13.9 mmol), (4-chloromethyl-phenyl)- methanol (2.21 g, 13.9 mmol) and triphenylphosphine (4.49 g, 16.8 mmol) are dissolved in tetrahydrofuran (40 ml). The solution is cooled to 0C then diethylazodicarboxylate(6.47 ml, 16.6 mmol) is added. The mixture is stirred at 0C for 2 hours, then 1 hour at room temperature. The solvent is removed under vacuum and the residue is purified by flash chromatography (0 – 50% ethyl acetate in cyclohexane) to give the title compound (Yield 1 .72 g). LC (Method 2): tR = 4.40 min; Mass spectrum (ES+): m/z = 279 [M+H ]+

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

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; FRATTINI, Sara; BAKKER, Remko; GIOVANNINI, Riccardo; HAMPRECHT, Dieter; LINGARD, Iain; PAUTSCH, Alexander; WELLENZOHN, Bernd; (92 pag.)WO2017/72020; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 4149-06-8,Some common heterocyclic compound, 4149-06-8, name is 3-Amino-1-phenyl-1H-pyrazol-5(4H)-one, molecular formula is C9H9N3O, 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: The mixture of alpha,beta-unsaturated ketone 1, or 4 (1.0 mmol), 3-amino-1-phenyl-1H-pyrazol-5(4H)-one 2 (1.0 mmol), p-TSAxH2O (0.3mmol), MeCN (4mL), H2O (4mL) was put in a reaction flask under 80 C about 1-3 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be precipitated out at same time. Then, it was filtered, washed thoroughly with MeCN. The products were recrystallized from DMF.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Amino-1-phenyl-1H-pyrazol-5(4H)-one, its application will become more common.

Reference:
Article; Xu, Shuangshuang; Wang, Zhansheng; Li, Xiuling; Rong, Liangce; Tu, Shu-Jiang; Tetrahedron; vol. 72; 38; (2016); p. 5754 – 5761;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 52222-73-8, name is 4-(Trifluoromethyl)-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., name: 4-(Trifluoromethyl)-1H-pyrazole

To a solution of 2-fluoro-3-hydroxybenzonitrile (0.92 g, 6.7 mmol) and4-(trifluoromethyl)-JH-pyrazole (1.0 g, 7.3 mmol) dissolved in 14 mL ofN,N-dimethylacetamide under a nitrogen atmosphere was added powdered potassium carbonate (2.78 g, 20.1 mmol). The resulting mixture was then heated at 153 C for 18 h. The cooled reaction mixture was diluted with de-ionized water and ethyl acetate and the layers separated. The aqueous layer was extracted (4X) with ethyl acetate, and the combined organic layers were washed (3X) with de-ionized water followed by brine. The combinedorganic layers were dried over Mg504, filtered and concentrated to give 1.58 g of an oil. Chromatography through 40 g of silica gel eluting with a gradient of 20 to 40% ethyl acetate in hexanes to give 1.37 g of a solid. The solid was filtered from hexanes to give 680 mg of the title compound.1H NMR oe 9.86 (bs, 1H), 8.64 (s, 1H), 8.07 (s, 1H), 7.40 (m, 2H), 7.37 (m, 1H).

According to the analysis of related databases, 52222-73-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; SHARPE, Paula Louise; STEVENSON, Thomas Martin; DEPREZ, Nicholas Ryan; REDDY, Ravisekhara P.; CHITTABOINA, Srinivas; WO2015/89003; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 37687-24-4, name is Diethyl 3,5-pyrazoledicarboxylate, belongs to pyrazoles-derivatives 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 37687-24-4, Product Details of 37687-24-4

In 250 mL of acetonitrile was dissolved 2-chloro-1-(i-methyl-1H- pyrazol-4-yl)ethanone (18.3 g, 115 mmol) and diethyl iH-pyrazole-3,5-dicarboxylate (24.5 g, 115 mmol) before finely ground K2C03 (31.9 g, 231 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was filtered and the cake was washed with acetonitrile (100 mL). The filtrate was concentrated in vacuo to a thick oil. The oil was dissolved in EtOAc (80 mL), and heptane (200 mL) was added slowly with stirring. The resultant solids were stirred for 2 hours, then filtered and washed with heptane. The solids were dried in a vacuum oven to afford diethyl 1-(2-(i-methyl-1H-pyrazol-4- yl)-2-oxoethyl)-1H-pyrazole-3,5-dicarboxylate (26.4 g, 77.4 mmol, 67.1 % yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Diethyl 3,5-pyrazoledicarboxylate, and friends who are interested can also refer to it.

Reference:
Patent; ARRAY BIOPHARMA INC.; CELGENE CORPORATION; ALLEN, Shelley; BOYS, Mark Laurence; CHICARELLI, Mark J.; FELL, Jay Bradford; FISCHER, John P.; GAUDINO, John; HICKEN, Erik James; HINKLIN, Ronald Jay; KRASER, Christopher F.; LAIRD, Ellen; ROBINSON, John E.; TANG, Tony P.; BURGESS, Laurence E.; RIEGER, Robert Andrew; PHENEGER, Jed; SATOH, Yoshitaka; LEFTHERIS, Katerina; RAHEJA, Raj K.; BENNETT, Brydon L.; (223 pag.)WO2016/90285; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 288-13-1, name is 1H-Pyrazole, belongs to pyrazoles-derivatives 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 288-13-1, Safety of 1H-Pyrazole

To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml of acetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs2CO3 (16.5 g, 0.050 mol), Cu2O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g, 0.006 mol) under N2 atmosphere. The reaction mass was refluxed for 24 hrs at 80 C. The reaction mass was concentrated and the crude was purified by column chromatography using ethyl acetate and hexane (1:1) to afford the pyrazolyl pyridine as a dark brown liquid (2 g, 43%): 1H NMR (400 MHz, CDCl3) delta 8.99 (d, J=2.8 Hz, 1H), 8.48 (dd, J=4.8, 1.2 Hz, 1H), 8.11-8.08 (m, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.38-7.35 (m, 1H), 6.53 (t, J=1.2 Hz, 1H); MS (m/z) 146 [M+1].

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; Dow Agrosciences LLC; Niyaz, Noormohamed M.; Garizi, Negar; Zhang, Yu; Trullinger, Tony K.; Hunter, Ricky; Buysse, Ann M.; Kubota, Asako; LePlae, Jr., Paul Renee; Knueppel, Daniel; Lowe, Christian T.; Pernich, Dan; Demeter, David A.; Johnson, Timothy C.; US2013/109566; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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 500011-84-7 as follows. COA of Formula: C5H8BrN3O2S

To trifluoroacetic acid (70 mL) was slowly added [3-BROMO N, N DIMETHYL-1H] [PYRAZOLE-L-SULFONAMIDE] (i. e. the bromopyrazole product of Step B) (57.04 g). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated at reduced pressure. The residue was taken up in hexane, insoluble solids were filtered off, and the hexane was evaporated to afford the crude product as an oil. The crude product was further purified by chromatography on silica gel using ethyl acetate/dichloromethane (10: 90) as eluent to afford an oil. The oil was taken up in dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with dichloromethane [(3X),] dried over magnesium sulfate and concentrated to afford the title product as a white solid (25.9 g), m. p. [61-64 C.] 1H NMR (CDC13) 8 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H).

According to the analysis of related databases, 500011-84-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; E.I. DU PONT DE NEMOURS AND COMPANY; WO2004/11447; (2004); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 1280210-79-8,Some common heterocyclic compound, 1280210-79-8, name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, molecular formula is C10H15N3O2, 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.

4,6-Dihydro-2H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester (0.50 g, 2.39 mmol) was dissolved in tetrahydrofuran (15 mL).Nitrogen protection,Sodium hydride (0.19 g, 4.77 mmol, 60%) was added at 0 C, and the mixture was slowly warmed to room temperature for 1 hour.Cool down to 0 C,Thiophene-2-sulfonyl chloride (0.65 g, 3.58 mmol) was added and allowed to react at room temperature for 15 hours.The reaction was quenched with water (10 mL) EtOAc.The combined organic phases were washed with a saturated sodium chloride solution (10 mL).Dry over anhydrous sodium sulfate and concentrate by suction filtration.The residue was subjected to silica gel column chromatography[ethyl acetate/petroleum ether (v/v) = 1/4] purified,The title compound was obtained (0.71 g, 84%).It is a white solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, its application will become more common.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Ruyuan Yong Xing Technology Services Co., Ltd.; Li Jianhao; Gu Zheng; Deng Xinshan; Tang Wanjun; Zhang Zongyuan; Kang Panpan; Yuan Weihui; Peng Fei; (49 pag.)CN109942583; (2019); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics