Tag: M.W:200-300

Synthetic Route of 1082745-50-3, These common heterocyclic compound, 1082745-50-3, name is 5-Amino-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxamide, 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 a suspension of 0.132 g (0.63mmol) of 5-amino-l-(tetrahydro-pyran-4-yl)-l-H-pyrazole-4- carboxylic acid amide (see PCT patent application WO2010/026214) in dry EtOH (1.5mL), 0.066 g (1.66 mmol) of sodium hydride (60 % suspension in mineral oil) were added at room temperature under nitrogen. After lOmin, 0.181mg (0.945mmol) of Example 13 A were added and the reaction mixture was heated to 140C for 40 min in a microwave oven (Power 100W). The reaction mixture was then diluted with DCM, water was added, organics separated and dried over sodiumsulphate. Organics were evaporated under reduced pressure and the crude purified by flash cromatography (DCM/IPA 98:2) to obtain the title compound as a white solid. (54mg, 32%).HPLC-MS (Method lEh): R, = 8.01 minMS (APCI pos): m/z = 352 (M+H)+

Statistics shows that 5-Amino-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxamide is playing an increasingly important role. we look forward to future research findings about 1082745-50-3.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HEINE, Niklas; EICKMEIER, Christian; FERRARA, Marco; GIOVANNINI, Riccardo; ROSENBROCK, Holger; SCHAENZLE, Gerhard; WO2012/20022; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 13808-65-6, 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. 13808-65-6 name is 4-Bromo-3-phenyl-1H-pyrazole, 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.

[0164] In a microwave tube was placed ethyl 2-bromothiazole-4-carboxylate (1058 mg, 4.48 mmol), 3-bromo-4-phenyl-1H-pyrrole (995 mg, 4.48 mmol), and K2C03 (929 mg, 6.72 mmol). The tube was sealed and DMSO (4 ml) was added. The mixture was heated at 120C for 4 h. The mixture was poured into vigorously stirred H20 (100 mL), and the solid was filtered, triturated with H20, and dried. The solid was re-dissolved in EtOAc and filtered. Some undissolved material was the hydrolized acid. The filtrate was concentrated and triturated with ca. 3% EtOAc/hexane to give ethyl 2-(4-bromo-3-phenyl- 1H-pyrazol- 1- yl)thiazole-4-carboxylate (1329 mg, 3.51 mmol, 78% yield).

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

Reference:
Patent; THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES; VANDERBILT UNIVERSITY; MALONEY, David J.; JADHAV, Ajit; BANTUKALLU, Ganesha Rai; BRIMACOMBE, Kyle Ryan; MOTT, Bryan T.; YANG, Shyh Ming; URBAN, Daniel Jason; HU, Xin; SIMEONOV, Anton; KOUZNETSOVA, Jennifer L.; WATERSON, Alex Gregory; SULIKOWSKI, Gary Allen; KIM, Kwangho; CHRISTOV, Plamen; JANA, Somnath; (387 pag.)WO2016/109559; (2016); 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.

To a solution of tert-butyl 4,6-dihydropyrrolo[3,4- c]pyrazole-5(2H)-carboxylate (15.0 g, 71.8 mmol) in DMF (150 mL) was added NaH (60% in mineral oil) (8.6 g, 215.4 mmol) while the reaction mixture was cooled with an ice bath. When the addition was complete, the resulting mixture was allowed to warm to room temperature and was stirred at room temperature for 30 min. At this point, l-bromo-2- methoxyethane (19.8 g, 143.6 mmol) was added into the reaction mixture, and stirring was continued at room temperature for 2 h. The reaction mixture was then quenched with water (300 mL), and extracted with EtOAc (150 mL x 3). The combined organic layer was washed with brine (100 mL x 3), dried over anhydrous Na2S04 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM : MeOH = 100 : 1 ~ 30 : 1) to give a mixture of 122 and 122-A (19.0 g, 99%) as a colorless oil. MS 268.2 [M + H]+. [0072] Synthesis of 123 and 123-A. To a solution of 122 and 122-A (6.5 g, 24.3 mmol) in DCM (60 mL) cooled with an ice bath was added TFA (30 mL). The reaction mixture was stirred at room temperature for 1 h, whereupon the solvent was removed in vacuo to give 123 and 123-A as a crude product mixture which was used directly in the next step without further purification. MS 168.1 [M+H]+. (0114) [0073] Synthesis of 124 and 124-A. To a solution of 123 and 123-A (24.3 mmol, crude product from last step) and A4 (9.3 g, 20.3 mmol) in DMSO (200 mL) was added Na2C03 (21.5 g, 203 mmol), and the reaction mixture was stirred at room temperature for 4 h. The mixture was then diluted with water (400 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (100 mL x 3), dried over anhydrous Na2S04 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM : MeOH = 100 : 1 ~ 30 : 1) to give a mixture of 124 and 124-A (4.5 g, 50%) as a yellow solid. MS 411.0, 413.1 [M+H]+.

The synthetic route of 1280210-79-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RODIN THERAPEUTICS, INC; FULLER, Nathan, Oliver; LOWE, John, A.; (45 pag.)WO2019/32528; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 39806-90-1, name is 4-Iodo-1-methyl-1H-pyrazole, molecular formula is C4H5IN2, 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: 4-Iodo-1-methyl-1H-pyrazole

To a solution of 4-iodo-1-methyl-pyrazole (2.68 g, 12.9 mmol) and tert- butyl piperazine-1 -carboxylate (2.00 g, 10.7 mmol) in /-PrOH (40 ml_), ethylene glycol (0.66 g, 10.7 mmol), Cul (0.41 g, 2.15 mmol) and K3P04 (9.12 g, 43.0 mmol) were added. The reaction mixture was heated in sealed tube at 100C for 20h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was concentrated in vacuo. The residue was diluted with H2O (150 ml_) and extracted with EtOAc (3 * 100 ml_). The organic layer was separated, washed with brine (100 ml_), dried over anhydrous Na2SC>4 and concentrated in vacuo. The crude residue obtained was purified by column chromatography (silica, 100-200 mesh, 0 to 2% MeOH in DCM) to afford tert-butyl 4-(1-methylpyrazol-4- yl)piperazine-1-carboxylate (0.93 g, 33%) as off-white solid. MS (ESI) m/e [M+H]7Rt/%: 267.00/2.45/82.5%. 1H NMR (400 MHz, CDCI3) 51.49 (s, 9H) 2.84 – 2.92 (m, 4H) 3.53 – 3.60 (m, 4H) 3.84 (s, 3H) 6.95 (s, 1 H) 7.21 (s, 1 H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 39806-90-1, its application will become more common.

Reference:
Patent; UCB BIOPHARMA SPRL; HALL, Adrian; (62 pag.)WO2018/138086; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 51516-70-2, name is 5-Amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile, 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 51516-70-2, category: pyrazoles-derivatives

General procedure: A mixture of theintermediate compounds 2 (1 mmol) and 3 (1 mmol) in ethanol(10 mL) was stirred at reflux for 2 h. After cooling to roomtemperature, the precipitated solid was filtered, and thenrecrystallized from ethanol to give the title compounds 5a-5p.

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, 5-Amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Lv, Xian-Hai; Ren, Zi-Li; Li, Dong-Dong; Ruan, Ban-Feng; Li, Qing-Shan; Chu, Ming-Jie; Ai, Cheng-Ying; Liu, Dao-Hong; Mo, Kai; Cao, Hai-Qun; Chinese Chemical Letters; vol. 28; 2; (2017); p. 377 – 382;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 1280210-79-8, 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. 1280210-79-8 name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-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.

To a solution of tert-butyl 4,6-dihydropyrrolo[3,4- c]pyrazole-5(2H)-carboxylate (15.0 g, 71.8 mmol) in DMF (150 mL) was added NaH (60% in mineral oil) (8.6 g, 215.4 mmol) while the reaction mixture was cooled with an ice bath. When the addition was complete, the resulting mixture was allowed to warm to room temperature and was stirred at room temperature for 30 min. At this point, l-bromo-2- methoxyethane (19.8 g, 143.6 mmol) was added into the reaction mixture, and stirring was continued at room temperature for 2 h. The reaction mixture was then quenched with water (300 mL), and extracted with EtOAc (150 mL x 3). The combined organic layer was washed with brine (100 mL x 3), dried over anhydrous Na2S04 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM : MeOH = 100 : 1 ~ 30 : 1) to give a mixture of 122 and 122-A (19.0 g, 99%) as a colorless oil. MS 268.2 [M + H]+. [0072] Synthesis of 123 and 123-A. To a solution of 122 and 122-A (6.5 g, 24.3 mmol) in DCM (60 mL) cooled with an ice bath was added TFA (30 mL). The reaction mixture was stirred at room temperature for 1 h, whereupon the solvent was removed in vacuo to give 123 and 123-A as a crude product mixture which was used directly in the next step without further purification. MS 168.1 [M+H]+. (0114) [0073] Synthesis of 124 and 124-A. To a solution of 123 and 123-A (24.3 mmol, crude product from last step) and A4 (9.3 g, 20.3 mmol) in DMSO (200 mL) was added Na2C03 (21.5 g, 203 mmol), and the reaction mixture was stirred at room temperature for 4 h. The mixture was then diluted with water (400 mL) and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (100 mL x 3), dried over anhydrous Na2S04 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (DCM : MeOH = 100 : 1 ~ 30 : 1) to give a mixture of 124 and 124-A (4.5 g, 50%) as a yellow solid. MS 411.0, 413.1 [M+H]+. Example 8. Synthesis of Compound 8 (0126) (0127) [0081] Synthesis of 129 and 129-A. A mixture of 124 and 124-A (350 mg, 0.85 mmol), 2-fluorophenylboronic acid (143 mg, 1.02 mmol) and K2CO3 (352 mg, 2.55 mmol) in dioxane/H20 (10 mL/2 mL) was treated with Pd(PPh3)4 (49 mg, 0.04 mmol) under a N2 atmosphere. The reaction mixture was stirred at 90 C for 3 h and then concentrated in vacuo. The crude residue was taken up in EtOAc (30 niL), and the resulting solution was washed with brine (10 mL x 3). The organic layer was dried over anhydrous Na2S04 and then concentrated in vacuo. The residue was purified by Prep-TLC (PE : EA = 5: 1) to give a mixture of 129 and 129-A (300 mg, 83%) as a yellow solid. MS 427.2 [M + H]+.

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(2H)-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; RODIN THERAPEUTICS, INC; FULLER, Nathan, Oliver; LOWE, John, A.; (45 pag.)WO2019/32528; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 106368-32-5, name is 5-Amino-1-(4-(methylsulfonyl)phenyl)-1H-pyrazole-4-carbonitrile, 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. Quality Control of 5-Amino-1-(4-(methylsulfonyl)phenyl)-1H-pyrazole-4-carbonitrile

General procedure: A mixture of 5-amino-1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-4-carbonitrile 5 (1.113 g, 5 mmol), the appropriate aldehyde (6, 5 mmol), and few drops of ethanol was added to morpholinium hydrogen sulphate (7, 0.4 g, 2 mmol). The mixture was heated in an oil bath for 5 h at 100 C. After completion of the reaction which was monitored by TLC, the solid product was filtered and crystallized from ethanol.

The synthetic route of 5-Amino-1-(4-(methylsulfonyl)phenyl)-1H-pyrazole-4-carbonitrile has been constantly updated, and we look forward to future research findings.

Reference:
Article; Abdellatif, Khaled R.A.; Elsaady, Mohammed T.; Abdel-Aziz, Salah A.; AbuSabah, Ahmed H.A.; Letters in drug design and discovery; vol. 14; 8; (2017); p. 930 – 937;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1029413-51-1, The chemical industry reduces the impact on the environment during synthesis 1029413-51-1, name is 4-Amino-1-(1-boc-azetidin-3-yl)-1H-pyrazole, I believe this compound will play a more active role in future production and life.

C) tert-butyl 3-(4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate To a solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (300 mg) obtained in Step E of Example 103, tert-butyl 3-(4-amino-1H-pyrazol-1-yl)azetidine-1-carboxylate (300 mg) obtained in Step B of Example 131, cesium carbonate (740 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (110 mg) in tetrahydrofuran (10 mL) was added tris(dibenzylideneacetone)dipalladium(0) (105 mg), and the mixture was stirred at 90C for 10 hr under argon atmosphere. The solvent was evaporated under reduced pressure, and the reaction mixture was poured into water, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) to give the title compound (310 mg). MS(ESI+): [M+H]+ 465.4.

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, 4-Amino-1-(1-boc-azetidin-3-yl)-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Takeda Pharmaceutical Company Limited; TSUKAMOTO, Tetsuya; OHBA, Yusuke; YUKAWA, Takafumi; NAGAMIYA, Hiroyuki; KAMEI, Taku; TOKUNAGA, Norihito; SAITOH, Morihisa; OKABE, Atsutoshi; EP2832734; (2015); A1;,
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. 345637-71-0, name is 2-(5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acid, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H7F3N2O2

To a solution of 5-methyl-3-(trifluoromethyl)-lH-pyrazole-l -acetic acid (0.8 g, 3.8 mmol) in dichloromethane (10 mL) was added oxalyl chloride (2.4 g, 19.2 mmol) and two drops of iV.TV-dimethylformamide, resulting in slight exothermicity. The reaction mixture was then heated at reflux for 15 minutes. The reaction mixture was concentrated in vacuo, and the residue was suspended in tetrahydrofuran (10 mL) and treated with a solution of 2-(4-piperidinyl)-4-thiazolecarboxaldehyde’ monohydrochloride (i.e. the product of Example 2, Step A) (1.1 g, 5.1 mmol) in tetrahydrofuran (10 mL), followed by dropwise addition of triethylamine (1.2 g, 11.9 mmol). The reaction mixture was stirred overnight at room temperature and then partitioned between 1 N aqueous hydrochloric acid and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with additional ethyl acetate (2 x 30 mL). The combined organic layers were washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, and brine. The organic layer was dried (MgSC^) and evaporated under reduced pressure to give 0.8 g of the title compound as a yellow oil. IH NMR (CDCl3) delta 1.79-1.90 (m, 2H)5 2.18-2.29 (m, 2H), 2.33 (s, 3H), 2.87-2.94 (m, IH)5 3.28-3.40 (m, 2H), 4.05-4.15 (m, IH), 4.56-4.64 (m, IH), 4.99-5.02 (m, 2H), 6.35 (s, IH), 8.12 (s, IH)5 IO-Ol (s, IH).; To a solution of 5-methyl-3-(trifluoromethyl)-li’-pyrazole-l -acetic acid (0.5 g,2.4 mmol) in dichloromethane (4 mL) was added oxalyl chloride (0.3 mL, 3.6 mmol) and one drop of N,LambdaT-dimethylformamide, resulting in slight exothermicity. The reaction mixture was then heated at reflux for 15 minutes. The reaction mixture was evaporated, and the resulting residue was suspended in dichloromethane (4 mL) and treated with a solution of 4-(4-ethenyl-2-thiazolyl)piperidine (i.e. the product of Example 4, Step B) (302 mg,1.5 mmol) in dichloromethane (2 mL), followed by addition of triethylamine (0.32 mL, 2.3 mmol). The reaction mixture was stirred overnight at room temperature, then concentrated, and purified by column chromatography on silica gel using 30-40 % ethyl acetate in hexanes as eluant to give 414 mg of the title compound as a white solid. IH NMR (CDCl3) 6 1.78 (m, 2H), 2.18 (m, 2H), 2.32 (s, 3H), 2.90 (br t, IH), 3.30 (m, 2H),4.03 (d, IH), 4.55 (d, IH), 5.00 (m, 2H), 5.35 (d, IH), 6.02 (d, IH), 6.33 (s, IH), 6.68 (dd,IH)5 7.01 (s, IH).

According to the analysis of related databases, 345637-71-0, 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; WO2008/13622; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 39806-90-1,Some common heterocyclic compound, 39806-90-1, name is 4-Iodo-1-methyl-1H-pyrazole, molecular formula is C4H5IN2, 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: 4-Iodo-1-methyl-1H-pyrazole 1 (101 mg, 0.5 mmol) and phenylboronic 2 (59 mg, 0.5 mmol) were dissolved in DME (3 mL) and H2O (1.2 mL) in a microwave vial under a nitrogen atmosphere. Pd(PPh3)4 (2 mmol%, 11.6 mg) and Cs2CO3 (407.3 mg, 1.25 mmol) were added, and the reaction mixture was irradiated in a microwave apparatus at 90 C for 5-12 min. After the reaction mixture was cooled to ambient temperature, the product was concentrated, and the crude mixture was purified by silica gel column chromatography using petroleum ether/acetone as eluent to give the title compound.

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

Reference:
Article; Cheng, Hua; Wu, Qiong-You; Han, Fan; Yang, Guang-Fu; Chinese Chemical Letters; vol. 25; 5; (2014); p. 705 – 709;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics