Category: pyrazoles-derivatives

Reference of 1239363-40-6,Some common heterocyclic compound, 1239363-40-6, name is 1-Cyclopropyl-4-iodo-1H-pyrazole, molecular formula is C6H7IN2, 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 potassium phosphate tribasic (792 mg, 3.73 mmol) and l-cyclopropyl-4-iodo-lH- pyrazole (437 mg, 1.866 mmol) in DMSO (10 mL) were added intermediate 41.4 (530 mg, 1.244 mmol), Irans-N 1.N2-dimethylcycloheane- 1.2-diamine (35.4 mg, 0.249 mmol) and copper(I) iodide (237 mg, 1.244 mmol) at room temperature. The mixture was stirred for 36 h at 90C under N2 atmosphere. 16% NEL aqueous (20 mL) was added to the mixture and this mixture was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and filtered. The filtrate was concentrated in vacuo to give intermediate 41.5, 6-(l-(4-(benzyloxy)-3-methyltetrahydrofuran-3-yl)piperidin-4-yl)-5-chloro-l-(l-cyclopropyl- lH-pyrazol-4-yl)-lH-indazole. MS (ESI) m/z calc?d for C30H35CIN5O2 [M+H] + 532 found 532.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Cyclopropyl-4-iodo-1H-pyrazole, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; SIMOV, Vladimir; KAPLAN, William, P.; ACTON, John, J., III; ARDOLINO, Michael, J.; CHEN, Joanna, L.; FULLER, Peter, H.; GUNAYDIN, Hakan; LI, Derun; LIU, Ping; LOGAN, Kaitlyn Marie; METHOT, Joey; MORRIELLO, Gregori, J.; NEELAMKAVIL, Santhosh, F.; TORRES, Luis; YAN, Xin; ZHOU, Hua; (0 pag.)WO2020/92136; (2020); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 199678-06-3, name is 4-(1-Methyl-1H-pyrazol-4-yl)benzoic acid, 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 199678-06-3, name: 4-(1-Methyl-1H-pyrazol-4-yl)benzoic acid

EXAMPLE 55 [4-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-(5H,11H-pyrrolo[2,1-c][1,4]-benzodiazepin-10-yl)-methanone oxalyl chloride (0.30 g) was added to a suspension of 4-(1-methyl-1H-pyrazol-4-yl)-benzoic acid (0.46 g) in dichloromethane (25 ml).. Two drops of dimethylformamide were added and the mixture was stirred for 18 hours at room temperature.. The resultant solution was evaporated to dryness to yield the crude acid chloride (0.57 g), which was utilized without further purification. The acid chloride was added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (0.37 g) and diisopropylethylamine (0.58 g) in dichloromethane (50 ml).. After 18 hours at room temperature, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate.. The dichloromethane solution was dried over anhydrous sodium sulfate and littered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane.. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred.. After cooling, the crystals were collected by filtration to yield the tide compound (0.38 g), m.p. 200-201 C; MS m/z: 368 (M)+.

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; Wyeth; EP1000062; (2004); B1;,
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

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

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

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

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 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

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

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