Category: pyrazoles-derivatives

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. 400755-44-4, name is 1-Ethylpyrazole-3-carboxylic Acid, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H8N2O2

To 1 -ethyl- 1H- pyrazole-3-carboxylic acid (5.01 g, 35.7 mmol) in benzene/MeOH (45 mL/10 mL) at 0 C was added drop wise (diazomethyl)trimethylsilane (19.7 mL, 39.3 mmol) in hexanes (2M). The cold bath was removed and the reaction mixture was stirred at ambient temperature for one hour. The reaction was quenched with the addition of acetic acid (0.25 mL). The mixture was concentrated under reduced pressure to give crude product, to which was added THF (50 mL) and the solution was cooled to 0 C. Lithium aluminum hydride (1.36 g, 35.7 mmol) was added cautiously to the solution. The cold bath was removed once the addition was complete. The mixture was stirred at ambient temperature for 2 hours and the reaction was quenched by careful addition of sodium sulfate decahydrate. The mixture was filtered through Celite, and the filter pad was washed with EtOAc (200 mL). The filtrate was concentrated under reduced pressure to give the product (4.41 g).

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; ARRAY BIOPHARMA INC.; BOYS, Mark Laurence; BRADLEY, Michael; DELISLE, Robert Kirk; HENNINGS, D. David; KENNEDY, April L.; MARMSATER, Fredrik P.; MEDINA, Matthew; MUNSON, Mark C.; RAST, Bryson; RIZZI, James P.; RODRIGUEZ, Martha E.; TOPALOV, George T.; ZHAO, Qian; WO2011/79076; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 35344-95-7, These common heterocyclic compound, 35344-95-7, name is 1H-Pyrazole-4-carbaldehyde, 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 nucleophile (1 mmol)was added to a solution of compound 1 or 2 (1 mmol) in MeCN or EtOH(10 ml) and the mixture was stirred at room temperature for 30 min (foradducts with 1) or 2?24 h (for adducts with 2). The precipitated productwas filtered off, washed with the same solvent (5 ml) and dried in air to give beige or brown solid adduct.

Statistics shows that 1H-Pyrazole-4-carbaldehyde is playing an increasingly important role. we look forward to future research findings about 35344-95-7.

Reference:
Article; Starosotnikov, Alexey M.; Shkaev, Dmitry V.; Bastrakov, Maxim A.; Fedyanin, Ivan V.; Shevelev, Svyatoslav A.; Dalinger, Igor L.; Mendeleev Communications; vol. 28; 6; (2018); p. 638 – 640;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 10010-93-2, name is 3-Methyl-5-(trifluoromethyl)-1H-pyrazole, 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 10010-93-2, Formula: C5H5F3N2

To a stirred solution of 5-methyl-3-(trifluoromethyl)-1H-pyrazole (199 mg, 1.328 mmol) in dry acetonitrile (7 mL) at room temp is added sodium hydride (63 mg of a 60% dispersion on mineral oil, 2.66 mmol). The mixture is stirred at room temp for 10 mins after which the initial effervescence had subsided to leave a colourless solution. A solution of trans-trifluoro-methanesulfonic acid 4-tert-butoxycarbonylamino-cyclohexylmethyl ester (Ex. 18 step 1) (400 mg, 1.107 mmol) in dry acetonitrile (4 mL) is then added and the mixture is stirred at room temp for 17 hours. The crude mixture is diluted with water (20 mL) and extracted with EtOAc (3×15 mL). The EtOAc extracts are combined, washed with sat. brine (30 mL), dried (MgSO4), filtered and evaporated to give a mixture of the title compounds as a pale yellow gum. This is used in the next step without further purification.

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

Reference:
Patent; Beattie, David; Colson, Anny-Odile; Culshaw, Andrew James; Sharp, Lisa; Stanley, Emily; Sviridenko, Lilya; US2010/35898; (2010); 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 149739-65-1 as follows. COA of Formula: C9H7BrN2

3-(3-Bromo-phenyl)-1H-pyrazole (17 g; 60.97 mmol; 1.00 eq.) dissolved in THF (5 mL) was added dropwise to a suspension of Sodium hydride (2.44 g; 60.97 mmol; 1.00 eq.) in THF (500 mL) maintained at 0C. The reaction mixture was stirred for 30 min before the dropwise addition of lodomethane (8.03 mL; 122 mmol; 2.00 eq.). It was then allowed to warm to RT and stirred for another 4h. Ice was added to quench the reaction and the mixture was extracted with ethyl acetate (30 mL x 2). Combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to give the title compound as a brown liquid (14.5 g, 99%). LC/MS: (max plot) 99 %; (254nm) 99 %; Rt 4.1 min; 239.0 (M+1).

According to the analysis of related databases, 149739-65-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Merck Patent GmbH; JORAND-LEBRUN, Catherine; JONES, Reinaldo; (112 pag.)EP3092225; (2019); B1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, 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 25016-11-9, COA of Formula: C5H6N2O

A solution of 1-methyl-1H-pyrazole-4-carbaldehyde (2.73 g, 24.80 mmol), (R)-2-methyl-2-propanesulfinamide (3.30 g, 27.30 mmol), and Ti(OiPr)4 (35.2 g, 37.1 mL, 0.124 mol) in THF (60 mL) was stirred with heating on a water bath at 50 C for 20 h. The resulting mixture was poured into water (100 mL) with stirring for 15 min, then filtered and the precipitate was washed twice with DCM. The filtrate was diluted with water (100 mL) and extracted with DCM (20 mL * 3). The combined extracts were dried over K2CO3, filtered through the pad of silica gel, and evaporated under reduced pressure and dried in vacuo to afford pure 2b 5.16 g (97%). = -130.7 (c 1, CHCl3), 1H NMR (400 MHz, CDCl3): delta 8.41 (s, 1H, CH=N), 7.83 (s, 1H, CHpyr), 7.78 (s, 1H, CHpyr), 3.89 (s, 3H, Me), 1.15 (s, 9H, tBu). 13C NMR (100 MHz, CDCl3): delta 154.28, 139.91, 132.14, 119.86, 57.30, 39.29, 22.39 3C. MS (70 eV, EI): m/z (%) = 214 (60) [MH]+, 157 (100), 130 (10), 109 (56), 108 (48), 83 (18), 82 (20), 81 (8), 41 (7). C9H15N3OS (213.3): calcd C 50.68, H 7.09, N 19.70, S 15.03, found C 50.42, H 7.11, N 19.55, S 14.88.

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-Methyl-1H-pyrazole-4-carbaldehyde, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Kuznetsov, Nikolai Yu.; Khrustalev, Victor N.; Strelkova, Tatyana V.; Bubnov, Yuri N.; Tetrahedron Asymmetry; vol. 25; 8; (2014); p. 667 – 676;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 139756-02-8, A common heterocyclic compound, 139756-02-8, name is 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide, molecular formula is C8H14N4O, 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.

General procedure: To a solution of 2-aminobenzamide (1.470 mmol, 1.0 eq.) was added to a solution of Terminal Alkyne (1.470 mmol, 1.0 eq.), Tosyl Azide, (1.470 mmol, 1.0eq.), CuI (0.147 mmol, 0.1 eq.), triethylamine (2.941 mmol, 2.0 eq.), in acetonitrile (10 ml) under N2 atmosphere. The mixture was stirred at room temperature for 12 h. After completion of the reaction (as indicated by TLC) the reaction mixture was poured into water (25 mL) and extracted with ethyl acetate (2×25 mL), dried over Na2SO4, concentrated under vacuum to get crude compound which was purified by column chromatography using a mixture of petroleum ether: ethyl acetate to give the desired product as a white solid.

The synthetic route of 139756-02-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Srishyalam; Devanna; Basaveswara Rao; Mulakayala, Naveen; Tetrahedron Letters; vol. 58; 30; (2017); p. 2889 – 2892;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 1018446-95-1, name is tert-Butyl 4-amino-1H-pyrazole-1-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 1018446-95-1, name: tert-Butyl 4-amino-1H-pyrazole-1-carboxylate

Intermediate 6 (220 mg, 0.67 mmol), triphosgene (66 mg, 0.22 mmol) and dry THF (5 mE) were sequentially added to a 10 mE three-necked flask. Under nitrogen protection, the reaction mixture was cooled to 00 C., and slowly added with DIPEA (173 mg, 1.34 mmol) dropwise. The reaction mixture was stirred for 10 mm. Then Intermediate 9 (240 mg, 1.34 mmol) was quickly added to the reaction mixture. The reaction mixture was stirred at room temperature overnight, concentrated, and purified by reversed phase column chromatography to give Intermediate 10 (95 mg, 32.4% yield) as a white solid. Because of there is TFA in solution, Intermediate 10 is converted to Compound of Formula Ic during lyophilization.

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, tert-Butyl 4-amino-1H-pyrazole-1-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; YIN, JIANMING; (11 pag.)US2019/169163; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 16034-46-1, 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. 16034-46-1, name is 1-Methyl-1H-pyrazole-5-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 1-methyl-1H-pyrazole-5-carboxylic acid (compound 4A, 1.99 g, 15.8 mmol), DIEA (5.95 g, 46.0 mmol) in CH2Cl2 (20 mL) was added EDCI (5.04 g, 26.3 mmol) and DMAP (1.93 g, 15.8 mmol) at -5 C., the mixture was stirred at -5 C. for 30 min under N2. Then 2-methyl-4-nitroaniline (compound 15, 2.00 g, 13.1 mmol) was added, the mixture was stirred at -5 C. for 30 min, then warmed to 25 C., stirred for 11 hrs. TLC (petroleum ether:ethyl acetate=1:1, Rf=0.55) showed starting material consumed completely. The mixture was concentrated in vacuum to give light yellow oil. The oil was purified by silica gel column chromatograph (petroleum ether:ethyl acetate=100:0 to 50:50) to give 1-methyl-N-(2-methyl-4-nitrophenyl)-1H-pyrazole-5-carboxamide (compound 16, 2.60 g, 76% yield) as light yellow solid.

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

Reference:
Patent; Kyn Therapeutics; Castro, Alfredo C.; Evans, Catherine Anne; (108 pag.)US2019/55218; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 18048-64-1, 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. 18048-64-1, name is 1-(3,4-Dimethylphenyl)-3-methyl-1H-pyrazol-5(4H)-one, This compound has unique chemical properties. The synthetic route is as follows.

Example 22; 3′- IN’-[ 1-(3,4-Dimethyl-phenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]- hydrazino}-2′-fluoro-biphenyl-3-carboxylic acid (Compound 122) was prepared as in Scheme III. 1H NMR (500MHz, Acetone-d6) 8 8.17 (t, J=1.7 Hz, 1H), 8.10 (ddd, J=7.7, 1.7,1.2 Hz, 1H), 7.81 (ddd, J=7.7, 1.7,1.2 Hz, 1H), 7.72 (m, 1H), 7.67 (t, J=7.7 Hz, 1H), 7.62 (d, J=1.9 Hz, 1H), 7.58 (m, 1H), 7.57 (m, 1H), 7.52 (m, 1H), 7.40 (m, 1H), 7.19 (d, J=8.2 Hz, 1H), 2.29 (s, 3H), 2.25 (s, 3H), 2.13 (s, 3H).

The chemical industry reduces the impact on the environment during synthesis 1-(3,4-Dimethylphenyl)-3-methyl-1H-pyrazol-5(4H)-one. I believe this compound will play a more active role in future production and life.

Reference:
Patent; LIGAND PHARMACEUTICALS INC.; WO2005/118551; (2005); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 31728-75-3, A common heterocyclic compound, 31728-75-3, name is 1,5-Dimethyl-1H-pyrazole-4-carboxylic acid, molecular formula is C6H8N2O2, 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.

Under an atmosphere of argon, diisopropylethylamine (3.49 ml) and diphenylphosphoryl azide (2.37 ml) were added in turn to a stirred mixture of 1,5-dimethyl-1H-pyrazole-4-carboxylic acid (1.4 g), tert-butanol (4 ml) and 1,4-dioxane (40 ml) and the reaction mixture was stirred at ambient temperature for 10 minutes. The resultant mixture was heated to 110 C. for 3 hours. The solvent was evaporated and the reaction product was purified by column chromatography on silica using ethyl acetate as the eluent. There was thus obtained 4-(tert-butoxycarbonylamino)-1,5-dimethyl-1H-pyrazole (0.225 g); 1H NMR: (DMSOd6) 1.4 (s, 9H), 2.2 (s, 3H), 3.55 (s, 1H), 6.0 (br s, 1H), 9.3 (br s, 1H).

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; Jung, Frederic Henri; Morgentin, Remy Robert; Ple, Patrick; US2009/76075; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics