Day: May 24, 2021

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. 40704-11-8, name is 3-Methyl-1H-pyrazole-4-carboxylic acid, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

Methyl5-methyl-1H-pyrazole-4-carboxylate. To a solution of 3-methyl-1H-pyrazole-4-carboxylic acid (1.26 g, 10 mmol) in MeOH (100 mL) was added thionyl chloride (5.73 g, 48 mmol) at 0 C. The mixture was stirred for 12 h and then concentrated in vacuo. The residue was quenched with sat. aq. sodium bicarbonate solution and extracted with EtOAc (3X). The combined organic phase was dried over sodium sulfate, filtered and concentrated to provide methyl 3-methyl-1H-pyrazole-4-carboxylate (0.8 g, 57%).

The synthetic route of 40704-11-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Gehling, Victor S.; Vaswani, Rishi G.; Nasveschuk, Christopher G.; Duplessis, Martin; Iyer, Priyadarshini; Balasubramanian, Srividya; Zhao, Feng; Good, Andrew C.; Campbell, Robert; Lee, Christina; Dakin, Les A.; Cook, Andrew S.; Gagnon, Alexandre; Harmange, Jean-Christophe; Audia, James E.; Cummings, Richard T.; Normant, Emmanuel; Trojer, Patrick; Albrecht, Brian K.; Bioorganic and Medicinal Chemistry Letters; vol. 25; 17; (2015); p. 3644 – 3649;,
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. 611239-23-7, name is tert-Butyl 1H-pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., Application In Synthesis of tert-Butyl 1H-pyrazole-4-carboxylate

To a solution of N-benzhydryl-6-chloro-4-methoxynicotinamide (200 mg, 0.6 mmol) in dioxane (16 mL) were added tert-butyl 1H-pyrazole-4- carboxylate (100 mg, 0.6 mmol), CuT (56 mg, 0.3 mmol), Cs2CO3 (550 mg, 1.7 mmol) and N,N-dimethylglycine (64 mg, 0.6 mmol). The mixture was stirred at 120C overnight. When TLC showed the reaction completed, the mixture was filtered. The filtrate was diluted with water (20 mL) and extractedwith EtOAc (40 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate and concentrated under vacuum. The residue was purified by prep. TLC (EtOAc /PE=3:1) to afford tert-butyl 1 -(5 -(benzhydrylcarbamoyl)-4- hydroxypyridin-2-yl)- 1 H-pyrazole-4- carboxylate. ?H NIVIR (CDC13,400 IVIHz) 12.87 (s, 1H), 8.88 (s, 1H), 8.50 (s, 1H), 8.02 (s, 1H), 7.55-7.50 (m, 1H), 7.42-7.27 (m, 11H), 6.41 (d, J= 7.3 Hz, 1H), 1.57 (s, 9H). LC/IVIS (m/z):471 (M+H).

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; MERCK SHARP & DOHME CORP.; UJJAINWALLA, Fez; TAN, John Qiang; DANG, Qun; SINZ, Christopher J.; WANG, Ming; CHEN, Yili; CAI, Jiaqiang; DU, Xiaoxing; (41 pag.)WO2016/54806; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 93608-11-8, 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. 93608-11-8, name is 3-Bromo-5-(trifluoromethyl)-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

3-Bromo-l-(4-nitrophenyl)-5-(trifluoromethyl)-l /-pyrazole 23b: To a stirred suspension of 22b (5.0 g, 23.3 mmol, 1.0 equiv) and anhydrous potassium carbonate (3.9 g, 27.9 mmol, 1.2 equiv) in DMF (116 mL), l-fluoro-4-nitrobenzene (2.5 mL, 23.5 mmol, 1.01 equiv) was added at 25 C, and the reaction mixture was heated to 80 C for 12 h. After cooling to 25 C, the reaction mixture was quenched with a saturated aqueous solution of ammonium chloride (20 mL), and the two phases were separated. The aqueous layer was extracted with ethyl acetate (3 chi 15 mL), and the combined organic layers were backwashed with water (2 chi 15 mL) and brine (15 mL), dried with anhydrous magnesium sulfate, and concentrated in vacuo. Flash column chromatography (silica gel, 8% to 20% ethyl acetate in hexanes) with a slow gradient to separate the undesired regioisomer afforded 23b (1.57 g, 4.66 mmol, 20%) as a white amorphous solid. 23b: Ri = 0.61 (silica gel, 20% ethyl acetate in hexanes); FT-IR (neat) V 3149, 2923, 2853, 1598, 1527, 1502, 1454, 1347, 1288, 1216, 1180, 1141, 1112, 1076, 986, 963, 854, 812, 757, 689 cm 1; NMR (600 MHz, CDC13) delta = 8.37 (d, J = 9.0 Hz, 2 H), 7.71 (d, J = 9.0 Hz, 2 H), 6.93 (s, 1 H) ppm; 13C NMR (151 MHz, CDC13) 5 = 148.1, 143.1, 134.3 (q, J = 40.4 Hz), 128.6, 125.9, 124.9, 116.1 (q, J= 270.0 Hz), 113.3 (q, J= 2.6 Hz) ppm; HRMS (ESI) calcd for Ci0H5BrF3N3O2 [M+H]+ 335.9590 found 335.9588.

The synthetic route of 3-Bromo-5-(trifluoromethyl)-1H-pyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; WILLIAM MARSH RICE UNIVERSITY; NICOLAOU, Kyriacos, C.; RHOADES, Derek; WANG, Yanping; TOTOKOTSOPOULOS, Sotirios; (191 pag.)WO2017/66606; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 51516-68-8, name is 5-Amino-1-(3-chlorophenyl)-1H-pyrazole-4-carbonitrile, molecular formula is C10H7ClN4, 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. name: 5-Amino-1-(3-chlorophenyl)-1H-pyrazole-4-carbonitrile

General procedure: 5-amino-1-aryl-1H-pyrazole-4-carbonitriles 4(aei) (0.001 mol),2.0 mL of 1,2-diaminoethane (ethylenediamine) and carbon disulfide(0.004 mol) were added into a 50 mL round-bottom flaskadapted with a glass condenser. The mixture was kept at 110-115oCfor 12-14 hours. After that, the productwas poured into cold water,the precipitate was filtered out and washed with cold water. Thereactions were accompanied by means of TLC and dichloromethaneas eluent.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 51516-68-8, its application will become more common.

Reference:
Article; Monteiro; Lechuga; Lara; Souto; Vigano; Bourguignon; Calvet; Oliveira; Alves; Souza-Silva; Santos; Pereira; European Journal of Medicinal Chemistry; vol. 182; (2019);,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 873191-23-2,Some common heterocyclic compound, 873191-23-2, name is 5-(Bromomethyl)-1,3-dimethyl-1H-pyrazole, molecular formula is C6H9BrN2, 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 lycorine derivatives 10, 11 and 12 (0.1mmol) were dissolved in dry THF (10mL), and NaH (50mg, 2mmol) and 3-(bromomethyl)pyridine, 3-(Chloromethyl)-1,5-dimethyl-1H-pyrazole or 5-Bromomethyl-1,3-dimethyl-1H-pyrazole (1mmol) were added. The mixture was stirred at r. t. for 24h and quenched with H2O (50mL) in an ice bath. The solution was evaporated to remove the THF and extracted with CH2Cl2 (2×30mL). The organic layer was washed with saturated NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography using petroleum ether-EtOAc as the eluent to afford compounds 5, 6, 7, 8 and 9.

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

Reference:
Article; Chen, Duozhi; Zhang, Heng; Jing, Chenxu; He, Xiaoli; Yang, Bijuan; Cai, Jieyun; Zhou, Yunfu; Song, Xiaoming; Li, Lin; Hao, Xiaojiang; European Journal of Medicinal Chemistry; vol. 157; (2018); p. 1491 – 1499;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 54385-49-8, 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. 54385-49-8 name is 5-Amino-1H-pyrazole-3,4-dicarbonitrile, 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.

5-Amino-lH-pyrazole-3,4-dicarbonitrile (7.6 g, 57 mmol) was suspended in trimethylorthoformate (60 mL) in a round bottom flask fitted with a stirbar and reflux condenser. The flask was placed in an oil bath and the mixture was heated at reflux overnight. After cooling to rt the following morning, the reaction solution was concentrated under reduced pressure to afford an orange oil. The oil was dried under high vacuum with stirring for 2h. The residue was dissolved in MeOH (25 mL) and cooled under nitrogen in an ice-water bath. A solution of ammonia in MeOH (7.0 M, 65 mL, 460 mmol) was added. The resulting slightly opaque solution was warmed to rt and stirred overnight. The solids produced were isolated by suction filtration, washed with MeOH and dried under suction. The tan powder was transferred to a round bottom flask and dried under high vacuum and used without further purification (6.20 g, 68%, 2 steps). LCMS (AA): m/z 161 (M+H); 1H MR (300 MHz, i-DMSO) delta 8.04 (s, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Amino-1H-pyrazole-3,4-dicarbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; MILLENNIUM PHARMACEUTICALS, INC.; ADHIKARI, Sharmila; CALDERWOOD, Emily, Frances; ENGLAND, Dylan, Bradley; GOULD, Alexandra, E.; HARRISON, Sean, J.; HUANG, Shih-Chung; MA, Liting; (316 pag.)WO2018/89786; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 20157-44-2, 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 20157-44-2 as follows.

To a 10 mL sealed tube was placed substrate 1j (47.5 mg, 0.3 mmol, 1.0 equiv), and then the tube wasevacuated and backfilled with argon (x3). To the reaction tube were added 0.15 mL of toluene (2.0 M),norbornene (141.2 mg, 1.5 mmol, 5.0 equiv), RuH2(CO)(PPh3)3 (2.8 mg, 0.003 mmol, 1 mol%), andHSiEt3 (174.4 mg, 0.24 mL, 1.5 mmol, 5.0 equiv). The system was closed and stirred at 100 C for 20 h.After removal of the solvent under reduced pressure, the yield of arylsilane 2j was determined by 1HNMR analysis using 1,1,2,2-tetrachloroethane as an internal standard.

According to the analysis of related databases, 20157-44-2, the application of this compound in the production field has become more and more popular.

Reference:
Article; Mita, Tsuyoshi; Tanaka, Hiroyuki; Michigami, Kenichi; Sato, Yoshihiro; Synlett; vol. 25; 9; (2014); p. 1291 – 1294;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 75092-30-7, name is 4-Iodo-1-methyl-1H-pyrazole-5-carboxylic acid, molecular formula is C5H5IN2O2, 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. Formula: C5H5IN2O2

Step 1. 1-Methyl-4-[(4-methylphenyl)amino]-1H-pyrazole-5-carboxylic acid A mixture of 4-iodo-1-methyl-1H-pyrazole-5-carboxylic acid ((Y. A. Manaev et al., J. Gen. Chem. USSR. (Engl. Transl.), 1982, 52, 2291), 2.92 g, 11.6 mmol), p-toluidine (6.20 g, 57.9 mmol), and copper powder (1.17 g, 18.4 mmol) in 5% aqueous sodium carbonate (60 ml) was stirring at 100 C. for 5 h. After cooling to room temperature, diethyl ether (100 ml) and 2N aqueous sodium hydroxide (100 ml) were added. This mixture was filtered through a pad of Celite, which was washed with 2N sodium hydroxide (200 ml) and ether (100 ml). The separated aqueous layer was washed with ether (100 ml), filtered through a pad of Celite again, and acidified with concentrated hydrochloric acid. The precipitate was collected by filtration, and washed with water to give 1.77 g (76.6 mmol, 66%) of the title compound as a gray powder. MS (EI) m/z: 231 (M+). 1H-NMR (DMSO-d6) delta: 7.61 (1 H, s), 7.05 (2 H, d, J=8.6 Hz), 6.98 (2 H, d, J=8.9 Hz), 4.00 (3 H, s), 2.22 (3 H, s). Two signals due to NH and CO2H were not observed.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 75092-30-7, its application will become more common.

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

Application of 3273-44-7, 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. 3273-44-7 name is 5-Methyl-1H-pyrazole-3-carbaldehyde, 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: To a suspension of 5-methyl-1H-pyrazole-3-carbaldehyde (18; 2-6 equiv) in anhydrous THF (10 mL) (in the case of the synthesis of 1) or MeOH (in the case of the synthesis of 2-5 and 11), the corresponding derivative bearing one to three amino groups (17,21 25-289d,11 or 36,4c see Scheme 1 and Scheme 2) (1 equiv), dissolved in anhydrous MeOH (5 mL), was added. The resulting mixture was heated at reflux until a clear solution resulted and then stirred at r.t. (up to 4 days, TLC analysis). The resulting imines were reduced without further purification by addition of NaBH4 (3-9 equiv) in portions. After complete addition of the reducing agent, the reaction mixture was stirred for 24 h at r.t. and then the solvent was removed under reduced pressure. The residue was suspended in CHCl3-H2O (1:1, 10 mL) and stirred for 12 h at r.t. The resulting suspension was extracted with CHCl3 (3 × 20 mL), dried over MgSO4, and the solvent was removed. The crude product was purified by column chromatography.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Methyl-1H-pyrazole-3-carbaldehyde, and friends who are interested can also refer to it.

Reference:
Article; Koch, Niklas; Seichter, Wilhelm; Mazik, Monika; Synthesis; vol. 48; 17; (2016); p. 2757 – 2767;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 107862-65-7,Some common heterocyclic compound, 107862-65-7, name is 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole, molecular formula is C6H8N2, 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 solution of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (150 mg, 1.39 mmol) and sodium acetate (114 mg, 1.39 mmol) in acetic acid (1.5 mL) at 0 C. was added bromine (197.5 mg, 1.25 mmol). After 10 minutes, the reaction mixture was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×20 mL). The organic layers were combined, washed with 5% Na2S2O4, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (PE: EtOAc=6:1 to 4:1) to give the title compound (120 mg, yield 46.4%) as 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 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole, its application will become more common.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WILES, Jason, Allan; PHADKE, Avinash, S.; DESHPANDE, Milind; AGARWAK, Atul; CHEN, Dawei; GADHACHANDA, Venkat, Rao; HASHIMOTO, Akihiro; PAIS, Godwin; WANG, Qiuping; WANG, Xiangzhu; (905 pag.)WO2017/35353; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics