Day: September 23, 2021

Electric Literature of 1260243-04-6, The chemical industry reduces the impact on the environment during synthesis 1260243-04-6, name is Ethyl 5-amino-1H-pyrazole-4-carboxylate, I believe this compound will play a more active role in future production and life.

Intermediate 18: Ethyl 7-(tert-butyl)-5-(4-ethylphenyl)-4,7-dihydropyrazolo[1,5- a]pyrimidine-3-carboxylateTo a solution of Intermediate 17 (1 g, 4.620 mmol) and ethyl 5-amino-1 H-pyrazole-4- carboxylate (ALDRICH, 0.717 g, 4.620 mmol) in 2-(methyloxy)ethanol (10 mL) was added TFA (0.885 mL, 1 1 .560 mmol) with ice-water cooling. The reaction was refluxed overnight. LCMS showed reaction was finished. The mixture was diluted with EtOAc, washed with saturated NaHC03, water and brine, dried over MgS04 and concentrated in vacuo. Then, the crude material was purified by flash chromatography on silica gel (Merck cartridge, 20 g) and was eluted with mixtures of hexane/EtOAc (80:20). The desired fraction was collected and evaporated to obtain a yellow solid (1.1 g, 3.1 10 mmol, 67%). 1H NMR (400 MHz, CDCI3) delta ppm: 7.73 (s, 1 H), 7.44 (d, 2H), 7.25 (d, 2H), 5.09 (dd, 1 H), 4.78 (d, 1 H), 4.30 (q, 2H), 2.68 (q, 2H), 1.37 (t, 3H), 1.26 (t, 3H), 0.92 (s, 9H). [ES+ MS] m/z 353 (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, Ethyl 5-amino-1H-pyrazole-4-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; ALVAREZ-RUIZ, Emilio; BALLELL-PAGES, Lluis; CASTRO-PICHEL, Julia; ENCINAS, Lourdes; ESQUIVIAS, Jorge; GAMO-BENITO, Francisco Javier; GARCIA-PALANCAR, Maria Cruz; REMUINAN-BLANCO, Modesto Jesus; WO2012/143522; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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

Ethyl 1-(4-(hydroxymethyl)benzyl)-1H-pyrazole-4-carboxylate Combined ethyl 1H-pyrazole-4-carboxylate (2.31 g; 16.48 mmol; 1.00 eq.), [4-(chloromethyl)phenyl]methanol (2.58 g; 16.48 mmol; 1.00 eq.), DMAP (0.04 g; 0.33 mmol; 0.02 eq.), and potassium carbonate (4.55 g; 32.97 mmol; 2.00 eq.) in acetonitrile (30.00 ml). Heated the reaction to 90 C. for 2 hours. Let the reaction cool to rt. Diluted reaction with water, extracted with ethyl acetate, combined organics, dried with MgSO4, filtered, and concentrated. The residue was purified by silica gel column to give ethyl 1-(4-(hydroxymethyl)benzyl)-1H-pyrazole-4-carboxylate (3.7 g, 86%)1H NMR (400 MHz, Chloroform-d) delta 7.93 (d, J=0.7 Hz, 1H), 7.84 (d, J=0.7 Hz, 1H), 7.40-7.34 (d, J=6.2 Hz, 2H), 7.24 (d, J=6.2 Hz, 2H), 5.29 (s, 2H), 4.70 (s, 2H), 4.27 (q, J=7.1 Hz, 2H), 1.36-1.29 (m, 3H).

The synthetic route of 37622-90-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Global Blood Therapeutics, Inc.; Li, Zhe; Xu, Qing; Yu, Chul; Yee, Calvin; Gwaltney,, II, Stephen L.; Metcalf, Brian W.; Richards, Steven; Lardy, Matthew A.; Setti, Lina; Sham, Hing; US2015/315198; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 83-10-3, The chemical industry reduces the impact on the environment during synthesis 83-10-3, name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, I believe this compound will play a more active role in future production and life.

Take raw material 1 (0.01mol) and raw material p-aminophenol 2 (0.01mol) was dissolved in DMF 15mL, was addedEDC.HCl (5.75 g, 0.03 mmol) was added and the reaction stirred at room temperature for 8 h. After the reaction was completed, water was added to the reaction solution to precipitate a white solid After stirring for 15 min, the filter cake was washed with water to neutrality and dried in vacuo to give a white solid. Intermediate 3 was obtained in 94% yield.

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, 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Shanghai Pharmaceutical Industry Institute; China Pharmaceutical Industry Zongyuan; Li Jianqi; Huang Daowei; Wang Wenya; Zhang Zhiguo; Jiang Ling; (45 pag.)CN107286140; (2017); A;,
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. 1280210-79-8, name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 1280210-79-8

Synthesis of 244-A. To a solution of tert-butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)- carboxylate (1.40 g, 6.70 mmol) in DCM (10 mL) was added TFA (3 mL) dropwise under ice bath. Then the solution was stirred at room temperature 1 h. The solvent was removed in vacuo to give 244- A as a crude product

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; RODIN THERAPEUTICS, INC; JEFSON, Martin, R.; LOWE, John, A., III; DEY, Fabian; BERGMANN, Andreas; SCHOOP, Andreas; FULLER, Nathan, Oliver; (165 pag.)WO2017/7756; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 930-36-9,Some common heterocyclic compound, 930-36-9, name is 1-Methylpyrazole, molecular formula is C4H6N2, 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.

S1, under nitrogen atmosphere protection,100g of 1-methylpyrazole was added to 2L of tetrahydrofuran, stirred to dissolve to uniform state,Then cooled to minus 60 degrees,Then 2.5M concentration of n-butyllithium 600ml,Insulation below minus 60 degrees Celsius,After the addition of n-butyl lithium is completed, and then incubated 0.4h,Cooled to minus 65 degrees Celsius,100 mL of N, N-dimethylformamide was added dropwise,After dropping N, N-dimethylformamide overnight at room temperature,The whole was cooled to 0 degrees Celsius, 300ml deionized water was added dropwise after quenching.S2, extracted with 500 ml of ethyl acetate each time,Repeat 2 times to separate the organic phase,Each time with 500ml saturated brine wash,Repeat washing 2 times, with 50g anhydrous sodium sulfate drying 1h,Suction filtration, then decompression rotary steaming,The product from S2 step is 1-methyl-1H-pyrazole-5-carbaldehyde.

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

Reference:
Patent; Beijing Luhe Ningyuan Technology Co., Ltd.; Jiang Yongjun; Xing Lixin; Liu Bo; (11 pag.)CN106928143; (2017); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 158001-28-6,Some common heterocyclic compound, 158001-28-6, name is 5-Amino-1-(tert-butyl)-1H-pyrazole-4-carbonitrile, molecular formula is C8H12N4, 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.

A mixture of 5-amino-1-(tert-butyl)-1H-pyrazole-4-carbonitrile (8, 1.1 g, 6.7 mmol) in formamide (15 ml) under a nitrogen atmosphere was heated in a microwave at 180 C for 30 min. The mixture was extracted with EtOAc (3 x 30 ml) and the organic layer was washed successively with sodium carbonate (30 ml), water (30 ml) and brine (30 ml). The organic layer was dried with magnesium sulfate, filtered and concentrated via evaporation of the solvent under a reduced pressure. The product was isolated as a brown solid in 77 % yield (0.97 g, 5.1 mmol). 1H NMR (200 MHz, CDCl3) delta 8.31 (s, 1 H), 7.85 (s, 1 H), 6.17 (s, 2 H), 1.77 (s, 9 H); 13C NMR (50 MHz, CDCl3) delta 157.9, 154.4, 153.2, 128.9, 102.1, 60.4, 29.2; HRMS (CI) calcd for C9H13N5 (M) 191.1171, found 191.1180.

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

Reference:
Article; Todorovic, Nick; Awuah, Emelia; Shakya, Tushar; Wright, Gerard D.; Capretta, Alfredo; Tetrahedron Letters; vol. 52; 44; (2011); p. 5761 – 5763;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1453-58-3, A common heterocyclic compound, 1453-58-3, name is 3-Methylpyrazole, molecular formula is C4H6N2, 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.

A stirred solution of 3-methylpyrazole (82.1 g, 1.0 mol) in water (3.5 L) was heated to 70 °C. Potassium permanganate (111 g, 0.70 mol) was added in one portion, keeping the temperature near 70 °C. The reaction mixture was stirred for 1 h at 70 °C, and then a second portion of potassium permanganate (111 g) was added at 70 °C. After 1 h, a final portion of potassium permanganate (111 g) was added at 70 °C. The reaction mixture was stirred a further 2 h at 70 °C, and any unreacted oxidant was reduced by the dropwise addition of isopropanol. The reaction mixture was cooled to room temperature, filtered, the solid was rinsed with water, and the filtrate evaporated to 500 ML. The aqueous was chilled to 0 °C, acidified with concentrated HCI, filtered, the solid product washed with water, and dried under vacuum to provide pyrazole- 3-carboxylic acid as a white solid (64.4 g, 57percent).

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 & CO., INC.; WO2004/58702; (2004); A2;,
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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C4H3N3

To a solution of A26 (300mg, 729 umol, 1.00 Eq) in acetone (5 mL) was added K2CO3 (200 mg, 1.45 mmol, 2.0 Eq) and 1H-pyrazole -4-carbonitrile (81.3 mg, 874 umol, 1.2 Eq) at 25oC. The reaction mixture was stirred at 25C for 16 hrs. Then, TLC showed the material was disappeared. The mixture was diluted with water (20 mL) and extracted with EA (30 mL×2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuum. The residue was purified by silica gel chromatography( 100-200 mesh silica gel, petroleum ether/ethyl acetate =2/1) to afford A39 (245 mg, 549 umol) as a off-white solid. 1H NMR (A39): 400MHz delta 7.86 (s, 1H), 7.81 (s, 1H), 5.04-4.88 (m, 2H), 2.62-2.58 (m, 1H), 0.95 (s, 3H), 0.65 (s, 3H).

According to the analysis of related databases, 31108-57-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SAGE THERAPEUTICS, INC.; MARTINEZ BOTELLA, Gabriel; SALITURO, Francesco, G.; ROBICHAUD, Albert, Jean; HARRISON, Boyd, L.; (275 pag.)WO2016/61527; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 28466-26-4, 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. 28466-26-4 name is 4-Aminopyrazole, 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.

[00606] Synthesis of compound 1-78. Compound 1-78 was prepared from compounds 3.4 and 96.2 using protocol described in Example 94. . LCMS (ES, m/z): 440 [M+H]+; 1H-NMR (300 MHz, DMSO) delta 8.87 (1H, s), 7.82 (1H, brs), 7.52 (1H, brs), 5.71 (1H, d), 4.05-3.89 (1H, m), 3.58 (4H, brs), 3.01-2.95 (2H, m), 2.84-2.79 (2H, m), 2.50 (4H, m), 2.42-2.34 (2H, m), 2.26- 2.18 (1H, m), 2.05 (2H, d), 1.92 (2H, d), 1.47-1.30 (4H, m). [00599] Example 94. Synthesis of 2-(4-((4-(((lr,4r)-4-morpholinocyclohexyl)amino)-6,7- dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-2-yl)amino)-lH-pyrazol-l-yl)acetate, Example 1-76 [00600] To a solution of intermediate 3.4 (50 mg, 0.13 mmol, 1.00 equiv) and 2-(4-amino- lH-pyrazol-l-yl)acetic acid (36 mg, 0.26 mmol, 2.00 equiv) in isopropanol (5 mL) was added hydrochloric acid (4 M in dioxane, 0.1 mL) at room temperature. The reaction was stirred for 2 h at 140 C and irradiated in microwave. The resulting mixture was concentrated under vacuum and resulting crude was purified to yield compound 1-76 as a yellow solid. LCMS (ES, m/z) 540 [M+H]+. 1H NMR (300 MHz, d6-OMSO, ppm): delta 8.99 (s, 1H), 7.90 (s, 1H), 7.51 (s, 1H), 7.26-7.06 (m, 1H), 5.79-5.71 (m, 1H), 4.99-4.91 (m, 3H), 4.01-3.99 (m, 1H), 3.77-51 (m, 4H), 3.05-2.98 (m, 2H), 2.83-2.73 (m, 2H), 2.61-2.53 (m, 5H), 2.40-2.35 (m, 2H), 2.01-1.94 (m, 2H), 1.49-1.35 (m, 4H), 1.20-1.15 (m, 6H).

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

Reference:
Patent; NIMBUS IRIS, INC.; CHAUDHARY, Divya; KAPELLER-LIBERMANN, Rosana; WO2014/194242; (2014); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1260243-04-6, 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. 1260243-04-6, name is Ethyl 5-amino-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 3-amino-4-carbethoxy pyrazole (1, 4 g, 1 mmol, 1 equiv) in acetonitrile (60 mL) and sodium hyride (1.5 g, 2 equiv) was stirred in a 250 mL round bottom flask for 1 h under ice cold conditions. Benzylchloride (6 mmol, 1.5 equiv) was added to the reaction mixture and further stirred at room temperature for 12 h. The mixture was extracted with ethyl acetate (3 * 10 mL). The organics were washed, dried on anhydrous Na2SO4, evaporated on a rotary evaporator to afford the crude product. The crude product was recrystallized (MeOH) to get pure compound 6a. Yield: 60%, white solid; mp: 161-162 C; IR (KBr): 3465, 3301, 1693, 1605 cm-1; 1H NMR (400 MHz, DMSO-d6): delta = 1.24 (t, 3H, J = 6.96 Hz, CH3), 4.17 (q, 2H, J = 6.92 Hz, OCH2), 5.35 (s, 2H, CH2), 7.35-7.24 (m, 5H), 8.08 (s, 1H, CH); 13C NMR (100 MHz, DMSO-d6): delta = 55.09, 59.52, 98.09, 127.61, 127.78, 128.17, 128.25, 128.72, 128.93, 133.63, 137.28, 157.07, 164.14.

The chemical industry reduces the impact on the environment during synthesis Ethyl 5-amino-1H-pyrazole-4-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Article; Baviskar, Ashish T.; Banerjee, Uttam C.; Gupta, Mukesh; Singh, Rajveer; Kumar, Sunil; Gupta, Manish K.; Kumar, Sanjeev; Raut, Satish K.; Khullar, Madhu; Singh, Sandeep; Kumar, Raj; Bioorganic and Medicinal Chemistry; vol. 21; 18; (2013); p. 5782 – 5793;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics