Day: May 18, 2021

Application of 657428-42-7, 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. 657428-42-7 name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate, 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.

Step D: tert-Butyl 2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate A solution of tert-butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate (30.0 kg, 143 mol) in 2-methyltetrahydrofuran (384 mg) was vacuum purged with nitrogen back-fill three times. The, triethylamine (25.0 kg, 247 mol) was added and the batch cooled to -10-5 C. Then, methanesulfonyl chloride (21.4 kg, 187 mol) was slowly added over 2 h. After stirring for 1 h at room temperature, water (150 kg) was added drop-wise at 5-15 C. This was followed by addition of 1N HCl solution until the pH was 7. The resulting layers were separated and the aqueous extracted with 2-methyltetrahydrofuran (106 kg). The combined organics were washed with saturated brine (2*150 kg), dried with Na2SO4, filtered, and concentrated to 60-90 L. The resulting crude was dissolved in 2-methyltetrahydrofuran (381 kg) and charged with a solution of potassium tert-butoxide in THF (805 g in 6.6 kg THF). After stirring 1 h at room temperature under nitrogen, more potassium tert-butoxide in THF (329 g in 3.0 kg THF) was added and stirred for 1 h. Analytical analysis indicates that tert-butyl 2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate is the major regioisomer, so saturated brine (154 kg) was then added. After brief agitation, the layers are separated and the oragnics are washed with saturated brine (2*155 kg). The combined aqueous waste layers were then extracted with 2-methyltetrahydrofuran (103 kg). The combined organics were treated with activated carbon (8.75 kg), filtered, and dried with Na2SO4. This was then filtered and concentrated to 60-90 L. This slurry was then heated to dissolve solids at 40-50 C. and n-heptane was added (34 kg). After cooling to room temperature for 2-4 h, n-heptane (156 kg) was added and the slurry was then aged for 2-4 h at 0-5 C. The slurry was filtered and the cake washed with n-heptane. The solids were dried under vacuum at 45-55 C. to give tert-butyl 2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; Merck Sharp & Dohme Corp; Merck Sharp & Dohme Ltd.; Arroyo, Itzia Z.; Krueger, Davida; Chen, Ping; Moment, Aaron J.; Biftu, Tesfaye; Sheen, Faye; Zhang, Yanfeng; US9181262; (2015); B2;,
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. 75092-30-7, name is 4-Iodo-1-methyl-1H-pyrazole-5-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 75092-30-7

Step 1. 4-[(4-Fluorophenyl)amino]-1-methyl-1H-pyrazole-5-carboxylic acid A mixture of 4-iodo-1-methyl-1H-pyrazole-5-carboxylic acid ((Manaev, Yu. A. et al., J. Gen. Chem. USSR (Engl. Transl.), 1982, 52 (11), 2291), 500 mg, 1.98 mmol), 4-fluoroaniline (0.94 ml, 9.90 mmol), copper powder (200 mg) and 5% aqueous sodium carbonate (10 ml) was stirred for 16 h at 100 C. After cooling to room temperature, 2N aqueous sodium hydroxide (100 ml) and diethyl ether (50 ml) were added to the mixture. The mixture was filtered through a pad of Celite. The water layer was separated, washed with diethyl ether (50 ml) and acidified with concentrated hydrochloric acid. The formed precipitate was collected by filtration and dried to give 282 mg (61%) of the title compound as a white solid. Rf value: 0.50 (methanol/dichloromethane/acetic acid=1/10/2 drops). 1H-NMR (DMSO-d6) delta: 7.60 (1 H, s), 7.09-7.05 (4 H, m), 4.01 (3 H, s). Two signals due to NH and CO2H were not observed.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 75092-30-7.

Reference:
Patent; Kawamura, Kiyoshi; Mihara, Sachiko; Nukui, Seiji; Uchida, Chikara; US2003/130277; (2003); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 54006-63-2, 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. 54006-63-2, name is 5-(4-Chlorophenyl)-1H-pyrazole-3-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

Acid 68 (0.898 mmol), HOBt (0.898 mmol) and N,O-dimethylhydroxylamine hydrochloride (0.898 mmol) were dissolved in CH2Cl2 (5 mL) and stirred for 10 min. EDC (0.898 mmol) in 5 mL of CH2Cl2 was added dropwise over 20 mins in which the colorless reaction mixture was stirred for 48 hrs. at room temperature under nitrogen. The reaction mixture was diluted with 10 mL of CH2Cl2, washed 2 times with water and twice with brine. The organic layer was dried with Na2SO4 and concentrated to give the amide 69 as a light yellow solid, which was used in the next step without further purification.

The chemical industry reduces the impact on the environment during synthesis 5-(4-Chlorophenyl)-1H-pyrazole-3-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; The Burnham Institute; US2010/16292; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 105994-77-2, name is 4-Bromo-1-methyl-5-phenyl-1H-pyrazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 4-Bromo-1-methyl-5-phenyl-1H-pyrazole

General procedure: A mixture of 5.17 g of 4-chloro-1-ethyl-6-nitroquinolin-2(1H)-one, 4.26 g of cyclopropylboric acid monohydrate, 10.9 g of sodium carbonate, 0.44 g of bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II), 50 mL of ethylene glycol dimethyl ether, and 5.0 mL of water was heated to reflux under a nitrogen atmosphere for 3 hours. Thereafter, the reaction mixture was cooled to room temperature, and ethyl acetate and water were then added thereto. An organic layer was separated, was then successively washed with water and a saturated sodium chloride aqueous solution, and was then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. Diisopropyl ether, ethyl acetate and hexane were added to the obtained residue, and a solid was collected by filtration and was then washed with diisopropyl ether to obtain 4.81 g of 4-cyclopropyl-1-ethyl-6-nitroquinolin-2(1H)-one in the form of a slightly brown solid. 1H-NMR (CDCl3): 0.79-0.87 (2H, m), 1.15-1.24 (2H, m), 1.37 (3H, t, J=7.3 Hz), 2.11-2.23 (1H, m), 4.37 (2H, q, J=7. Hz), 6.54 (1H, s), 7.47 (1H, d, J=9.2 Hz), 8.42 (1H, dd, J=9.2, 2.6 Hz), 9.00 (1H, d, J=2.6 Hz).

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; FUJIFILM Corporation; FUJIFILM Toyama Chemical Co., Ltd.; NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY; MAKITA, Keiko; SAEKI, Kazunori; TANAKA, Tadashi; FUJINO, Masataka; NATSUME, Tohru; FURUYA, Kentaro; (120 pag.)US2019/314360; (2019); 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 4331-28-6 as follows. SDS of cas: 4331-28-6

To a mixture of 2-benzyl-6-(methylcarbamoyl)isonicotinic acid (251.8 mg, 0.93 mmol) and HATU(565.5 mg, 1.49 mmol) was added 1H-pyrazol-4-amine hydrochloride (166.0 mg, 1.39 mmol) andDMF (4 mL). DIPEA (0.570 mL, 3.26 mmol) was added and the mixture was stirred at rt for 3.5 h.The mixture was concentrated under a stream of nitrogen and then diluted with acetonitrile to a totalvolume of 5 mL and directly purified by MDAP (5 x 1 mL injection; high pH) and the required fractions(fraction 1 from each run) were evaporated under a stream of nitrogen. The residues were eachredissolved in methanol ( 5 mL), combined into a tarred vial and the solvent evaporated under a stream of nitrogen to give a pale yellow solid – 6-benzyl-N2-methyl-N4-(1H-pyrazol-4-yl)pyridine-2,4- dicarboxamide (198.9 mg, 0.59 mmol, 64 % yield)LCMS (2 mm High pH): Rt = 0.85 mi [MH]+ = 336.1.1H NMR (400 MHz, DMSO-d6) O ppm 12.71 (br. 5., 1 H), 10.88 (s, 1 H), 8.78 (q, J=4.5 Hz, 1H), 8.40 (d, J=1.5 Hz, 1 H), 8.02 (br. 5., 1 H), 7.90 (d, J=1.5 Hz, 1 H), 7.70 (br. 5., 1 H), 7.36 – 7.41 (m, 2 H), 7.29 – 7.36 (m, 2 H), 7.19 – 7.26 (m, 1 H), 4.25 (s, 2 H), 2.88 (d, J=4.9 Hz, 3 H)

According to the analysis of related databases, 4331-28-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (N.2) LIMITED; ATKINSON, Stephen John; DEMONT, Emmanuel Hubert; HARRISON, Lee Andrew; LEVERNIER, Etienne; PRESTON, Alexander G; SEAL, Jonathan, Thomas; WALL, Ian David; WATSON, Robert J; WOOLVEN, James Michael; (0 pag.)WO2018/158210; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 113808-86-9, 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. 113808-86-9, name is 3,5-Dimethylpyrazole-4-carboxylic Acid, This compound has unique chemical properties. The synthetic route is as follows.

Example 135 2-(((3R,4S)-1-(3,5-dimethyl-1H-pyrazole-4-carbonyl)-3-fluoropiperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile To a solution of 2-(((3R,4S)-3-fluoropiperidin-4-yl)oxy)-5-(4-((4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-1,3,5-triazin-2-yl)benzonitrile (35 mgs, 0.07 mmol) in DMF (1.0 mL) was added 3,5-Dimethyl-1H-pyrazole-4-carboxylic acid (19 mgs, 0.13 mmol), HATU (50 mgs, 0.13 mmol) and TEA (0.02 mL, 0.13 mmol). The above reaction mixture was stirred at room temperature for 2 h, evaporated under reduced pressure and purified via preparative HPLC (5-65% acetonitrile in water, 0.1% trifluoroacteic acid buffer) to yield the title compound. LCMS-ESI+ (m/z): [M+H]+ calcd for C34H37FN10O3: 652.7. found: 653.3 1H NMR (400 MHz, DMSO-d6) delta 10.74 (brs, 1H), 10.24-10.09 (m, 1H), 8.75 (s, 1H), 8.57 (m, 2H), 7.67-7.43 (m, 3H), 7.06 (d, J=9.6 Hz, 2H), 5.26-5.01 (m, 3H), 4.76 (m, 4H), 4.44 (m, 1H), 4.27-3.61 (m, 5H), 3.59-3.40 (m, 2H), 3.10-2.88 (m, 4H), 2.50 (s, 6H), 2.02-1.97 (m, 2H).

The chemical industry reduces the impact on the environment during synthesis 3,5-Dimethylpyrazole-4-carboxylic Acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Gilead Sciences, Inc.; Du, Zhimin; Guerrero, Juan A.; Kaplan, Joshua A.; Knox, JR., John E.; Lo, Jennifer R.; Mitchell, Scott A.; Naduthambi, Devan; Phillips, Barton W.; Venkataramani, Chandrasekar; Wang, Peiyuan; Watkins, William J.; Zhao, Zhongdong; (593 pag.)US2016/96827; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 25700-12-3, name is 3-(1H-Pyrazol-1-yl)pyridine, A new synthetic method of this compound is introduced below., Recommanded Product: 25700-12-3

Step 2: Preparation of 3-(4-nitro-pyrazol-1-yl)-pyridine 3-Pyrazol-1-yl-pyridine (2 g, 0.032 mol) was dissolved in concentrated H2SO4 (32 mL 0.598 mmol) and cooled at -5 C. using an ice bath. To the reaction mass, a 1:1 mixture of concentrated HNO3 (30 mL, 0.673 mmol) and concentrated H2SO4 (30 ml, 15 Vol.) was added dropwise over a period of 30 min. Cooling was discontinued and the reaction mixture was stirred at room temperature overnight. After the reaction was complete, the mixture was poured over crushed ice and neutralized with saturated NaHCO3, filtered, washed with water and dried to furnish the nitro pyrazole as pale yellow solid (1.8 g, 68%): 1H NMR (400 MHz, DMSO-d6) delta 9.03 (d, J=2.8 Hz, 1H); 8.70 (dd, J=4.8, 1.6 Hz, 1H), 8.69 (s, 1H), 8.33 (s, 1H), 8.11-8.08 (m, 1H), 7.51 (dd, J=8.4, 4.8 Hz, 1H); MS (m/z) 191 [M+1].

The synthetic route of 25700-12-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dow AgroSciences LLC; Buysse, Ann M.; Niyaz, Noormohamed M.; Demeter, David A.; Zhang, Yu; Walsh, Martin J.; Kubota, Asako; Hunter, Ricky; Trullinger, Tony K.; Lowe, Christian T.; Knueppel, Daniel I.; Patny, Akshay; Garizi, Negar; LePlae, JR., Paul Renee; Wessels, Frank J.; Ross, JR., Ronald; DeAmicis, Carl; Borromeo, Peter; (118 pag.)US2016/60245; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 113808-86-9,Some common heterocyclic compound, 113808-86-9, name is 3,5-Dimethylpyrazole-4-carboxylic Acid, molecular formula is C6H8N2O2, 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.

Preparation of Examples 251-253; The piperazine Example 1 (220 mg), EDC (i.e., 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (245 mg), HOBT (i.e., 1-hydroxybenzotriazole) (172 mg), acid (108 mg), and JPr2NEt (206 mg) were taken up in CH3CN and stirred at 25C (18 h). The solution was partitioned15 between EtOAc and 1 N NaOH(aq.). The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration gave a solid. The solid was triturated with Et2O. The white solid was collected and dried to give 125 mg (42 %) of Example 251.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,5-Dimethylpyrazole-4-carboxylic Acid, its application will become more common.

Reference:
Patent; SCHERING CORPORATION; WO2006/60461; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 4027-57-0, name is Ethyl 5-methylpyrazole-3-carboxylate, 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 4027-57-0, Recommanded Product: 4027-57-0

A mixture of ethyl 5-methyl-1H-pyrazole-3-carboxylate (4.0 g, 25.95 mmol) and NBS (5.08 g, 28.54 mmol) in N,N-dimethylformamide (15 mL) was stirred at room temperature for 16 h. The mixture was taken up in EtOAc (200 mL) and the organics were washed with saturated brine solution. The organics were then separated and dried (Na2SO4) before concentrated to dryness. The crude was then purified by flash column chromatography (PE/EA=3/2) to give ethyl 4-bromo-5-methyl-1H-pyrazole-3-carboxylate (4.8 g, 79% yield) as a white solid. LCMS (ESI): [M+H]+=234.9.

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, Ethyl 5-methylpyrazole-3-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Genentech, Inc.; Chan, Bryan; Drobnick, Joy; Gazzard, Lewis; Heffron, Timothy; Liang, Jun; Malhotra, Sushant; Mendonca, Rohan; Rajapaksa, Naomi; Stivala, Craig; Tellis, John; Wang, Weiru; Wei, BinQing; Zhou, Aihe; Cartwright, Matthew W.; Lainchbury, Michael; Gancia, Emanuela; Seward, Eileen; Madin, Andrew; Favor, David; Fong, Kin Chiu; Hu, Yonghan; Good, Andrew; US2018/282282; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 4027-57-0, These common heterocyclic compound, 4027-57-0, name is Ethyl 5-methylpyrazole-3-carboxylate, 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.

Step 1 : Ethyl 1 -[5-(Aminosulfonyl)pyridin-2-yl]-5-methyl-1 H-pyrazoIe-3-carboxylate |mm-1 ); To a solution of ethyl 3-methylpyrazole-5-carboxylate {500 mg, 3.24 mmol) in S mL of anhydrousDMSO was added 6-chIoropyridine-3-sulfonamide (623 mg, 3.24 mmol, Adams; J. Amer. Chem. Soc; 1949; 71; 387-390), followed by the addition of potassium tert-butoxide (400 mg, 3.56 mmol). The mixture was heated at 1000C in microwave for half hour. HPLC analysis showed one third of the starting material was consumed. The mixture was heated at 1000C for one more hour and diluted with water (50 mL) with rapidly stirring. The resultant suspension was filtered. The white solid was washed with water and dried under vacuum to give the title compound mm-1 (0.75 g, yield 75%), which was used without further purification. NMR provided in Table.The regiochemistry was confirmed with a 2D NOESY 1H NMR experiment that displayed a relationship as depicted on the structure below:Elemental Analysis: Calcd for C12H14N4O4S: C, 46.44; H, 4.55; N, 18.05. Found: C, 46.48; H, 4.56; N, 17.96.

The synthetic route of 4027-57-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER PRODUCTS INC.; WO2008/17932; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics