Category: pyrazoles-derivatives

Adding a certain compound to certain chemical reactions, such as: 92-43-3, name is 1-Phenyl-3-pyrazolidinone, 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 92-43-3, Computed Properties of C9H10N2O

1-Phenylpyrrolidin-3-one (82.99mmoM.0eq)Dissolved with 5% aqueous sodium hydroxide solution,Add ferric chloride hexahydrate (16.60 mmol, 0.2 eq), and pass the system to oxygen and keep the temperature at 80 C. After the reaction is completed, add water to the reaction solution to quench the reaction, and adjust RhoEta=1~2 with hydrochloric acid. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate.Concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: PE: EpsilonAlpha = 2:1)The pale yellow solid product 1-phenyl-1H-pyrazol-3-ol (1.46 g, yield 11%)

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

Reference:
Patent; Shanghai Taihe International Trade Co., Ltd.; Du Yonglei; Lv Liang; Li Hongwei; Liu Shiqin; Liu Jiyong; Hou Shuang; Ma Wen; (36 pag.)CN108503587; (2018); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 51985-95-6, name is Methyl 5-hydroxy-1-methyl-1H-pyrazole-3-carboxylate, 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. Product Details of 51985-95-6

Methyl 5 -hydroxy- i-methyl- 1H-pyrazole-3 -carboxylate (I Med. Chem., 54:8174 (2011)) (0.35 g, 2.24 mmol), K2C03 (0.62 g, 4.48 mmol), and sodium chlorodifluoroacetate (0.684 g, 4.48 mmol) were dissolved in DMF (10 mL) and water (1 mL). The reaction was heated to 130 °C for 20 mm. The reaction was diluted with water (100 mL) and EtOAc (200 mL). The organic phase was separated, washed with water(5x) and brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (0-80percent EtOAc/Hex gradient) to give Intermediate 14A (0.3 73 g, 81percent yield) as a colorless syrup. MS(ESI) m/z: 207.0 (M+H) ?H NMR: (400 MHz, CDC13) oe ppm 6.44 (t, J=i.0 Hz, 1H), 6.46 (t, J=72.2 Hz, 1H), 3.92 (s, 3H), 3.82 (s, 3H); ?9F-NMR:(376 MHz, CDC13) oe ppm -84.02 (s, 2F).

The synthetic route of Methyl 5-hydroxy-1-methyl-1H-pyrazole-3-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; LADZIATA, Vladimir; GLUNZ, Peter W.; HU, Zilun; WANG, Yufeng; (0 pag.)WO2016/10950; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 13599-12-7,Some common heterocyclic compound, 13599-12-7, name is Ethyl 3-phenyl-1H-pyrazole-5-carboxylate, molecular formula is C12H12N2O2, 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.

Ethyl 2,4-dioxo-4-phenylbutanoate (16b) (2.6 g, 9.1 mmol)Dissolved in 30mL of methanol, added 15mL lithium hydroxide monohydrate(0.5 g, 20.0 mmol) in water. The reaction was heated to 70 C until the hydrolysis was complete. Concentration under reduced pressure gave a solid suspension. 15 mL of water was added and the pH was adjusted to 3 with 1 N diluted hydrochloric acid. Filtering,The title compound 5-phenyl-1H-pyrazole-3-carboxylic acid (Intermediate 16) was obtained.Dark white solid (2.1 g, yield 89.5%).

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

Reference:
Patent; Tianjin Pharmaceutical Institute Co., Ltd.; Wei Qunchao; Zheng Zhichao; Wang Songhui; Zheng Xuemin; Li Lingjun; Liu Lei; Yuan Jing; Zhang Shijun; Li Yuquan; Huang Changjiang; (38 pag.)CN109721539; (2019); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 83-10-3, 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. 83-10-3 name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, 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.

EXAMPLE 1 6beta-[D,2-(2,3-dimethyl-1-phenyl-3-pyrazolin-5-one-4-carbonylamino)-2-phenyl]acetamido penicillanic acid, sodium salt 2,3-Dimethyl-1-phenyl-3-pyrazolin-5-one-4-carboxylic acid (0.186 g, 0.8 mmol) in dry dimethyl formamide (D.M.F) (4 ml) was treated with triethylamine (0.12 ml, 0.8 mmol). The solution was cooled to -10 C. and isobutyl chloroformate (0.10 ml, 0.76 mmol) added dropwise. After 1 hour at -10 C., solids were removed by filtration and the solution added to ampicillin (anhydrous) (0.28 g, 0.8 mmol) premixed with triethylamine (0.12 ml, 0.8 mmol) in D.M.F. (10 ml) at -40 C. The solution was allowed to warm to 0 C., stirred for 90 minutes and poured into excess dry ether, with stirring. The precipitate was isolated and partitioned between ethyl acetate and water. The pH was adjusted to 7.5 (bicarbonate addition); the aqueous layer separated and acidified to pH 1.5 (HCl(5N)). Extraction with ethyl acetate, drying (Na2 SO4) and evaporation gave the title product as the free penicillanic acid (0.09 g, 20%), delta((CD3)2 CO) 1.50, 1.58 (2*3H, 2s, (CH3)2), 2.68 (3H, s,=C–CH3), 3.34 (3H, s, –NCH3), 4.36 (1H, s, C3 -proton), 5.53 (1H, d, J 4 Hz, C5 -proton), 5.71 (1H, d of d, J 4, 8 Hz, C6 -proton), 5.94 (1H, d, J 8 Hz, –CHCON–), 7.53 (10H, complex, aryl protons), 8.20 (1H, d, J 8 Hz, –NH–), 9.78 (1H, d, J 8 Hz, –NH–), 6.5-9 (1H, br, –CO2 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; Beecham Group p.l.c.; US4537886; (1985); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 1453-58-3, name is 3-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. name: 3-Methylpyrazole

1 – ( [2-(trimethylsilyl)ethoxy]methyl) – lH-pyrazole-3 -carbaldehyde was prepared as follows: 3-Methyl pyrazole (50 g, 0.61 mol) was placed in a 5 L round-bottom flask equipped with mechanical stirrer. 3 L of water was added and heated to 80 C. KMn04 (211.90 g, 1.34 mol) was added portion wise and refluxed for 4.5 h. After stirring at rt overnight, solid was filtered and washed with water. The water was removed in vacuo and 100 mL of water was kept in the flask which was acidified with 1 N HCl to pH 4. It was extracted with EtOAc (2x 1L), washed with brine (2×150 mL), dried over MgS04, filtered and removed in vacuo to yield 1H-pyrazole-3-carboxylic acid (38 g, 56percent) as a white solid. 38 g (0.34 mol) of IH-pyrazole-3-carboxylic acid was refluxed in anhydrous ethanol (1 L) and conc. sulfuric acid (60 mL) for 20 h under nitrogen. Ethanol was removed and crude was basified to pH 8. Precipitated solid was filtered. The filtrate was extracted with THF/CHC13 (2: 3, 3x 1 L), dried over MgS04, filtered and removed in vacuo to yield ethyl 1H-pyrazole-3- carboxylate (39 g, 82percent) as a white solid. To a suspension of ethyl 1H-pyrazole-3-carboxylate (4.42 g, 31.57 mmol) in 1,4-dioxane (140 mL) under N2 atmosphere at 0 C was added NaH (0.91 g, 37.88 mmol) and stirred for 15 min. Neat SEM-Cl (5.79 g, 34.73 mmol) was added drop wise to reaction mixture and stirred overnight at rt. It was quenched with water (30 mL) and excess 1,4-dioxane was removed in vacuo. The residue was extracted with EtOAc (2×250 mL), washed with water (1×50 mL), dried over MgS04, filtered and removed in vacuo to give crude ethyl 1 – {[2- (trimethylsilyl)ethoxy]methyl}-1H pyrazole-3-carboxylate (8.84 g) as a yellow oil. The crude material was used in next step without purification. To a suspension of LiAlH4 in THF (100 mL) at 0 C under N2 atmosphere was added a solution of ethyl 1- f [2-(trimethylsilyl)ethoxy]methyl}-1H pyrazole-3-carboxylate (8.88 g, 32.88 mmol) slowly. After addition was completed the cooling bath was removed and reaction mixture was stirred overnight. It was quenched with water (10 mL) carefully at 0 C. THF was removed and residue was diluted with DCM (250 mL) and organic layer was separated, dried over MgS04 and removed in vacuo. The crude material was plugged thru a pad of silica gel with EtOAc/hexanes (from 10percent to 100percent) to yield (1-{[2- (trimethylsilyl)ethoxy]methyl) -lH-pyrazol-3-yl)methanol (5.80 g, 77percent) as an yellow oil. 53.75 g (0.24 mol) of (1- f [2-(trirnethylsilyl)ethoxy]methyl}-1H pyrazol-3-yl)methanol was dissolved in THF and 122.97 g (1.41 mol) of Mn02 was added. The resulting mixture was refluxed for 60 h. Solid material was filtered through a pad of celite and washed with hot THF. The filtrate was removed in vacuo to give crude product. The crude was plugged thru a pad of silica gel and eluted with EtOAc/hexanes (from 20percent to 50percent) to yield 1-{[2- (trimethylsilyl)ethoxy]methyl}-1H pyrazole-3-carbaldehyde (50.88 g, 86.5percent) as a red oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1453-58-3, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; WO2005/111001; (2005); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 118430-74-3,Some common heterocyclic compound, 118430-74-3, name is 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, molecular formula is C7H11N3, 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.

Example 164 Synthesis of N-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2-(methoxymethyl)-9H-pyrimido[4,5-b]indol-4-amine (Cpd. No. 207) Pd2(dba)3 (18 mg) and BINAP (26 mg) were mixed in anhydrous toluene. And the mixture was heated at reflux for 3-4 minutes. This mixture was transferred into a round-bottom flask containing ZBB257 (60 mg), 3-cyclopropyl-1-methyl-1H-pyrazol-5-amine (84 mg), K3PO4 (130 mg), and toluene (2 mL). The mixture was heated at reflux for overnight before quenching with methanol. The reaction mixture was filtered and the mixture was purified by HPLC to yield ZBB259 as a CF3CO2H salt in 15 mg. ESI-MS calculated for C25H28N7O3 [M+H]+=474.22; Observed: 474.67. 1H NMR (300 MHz, MeOD) delta 7.50 (s, 1H), 7.38 (s, 1H), 6.11 (s, 1H), 4.69 (s, 2H), 3.90 (s, 3H), 3.76 (s, 3H), 3.59 (s, 3H), 2.34 (s, 3H), 2.17 (s, 3H), 2.05-1.86 (m, 1H), 1.04-0.95 (m, 2H), 0.78-0.72 (m, 2H).

The synthetic route of 118430-74-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF MICHIGAN; Wang, Shaomeng; Zhao, Yujun; Zhou, Bing; Aguilar, Angelo; Liu, Liu; Bai, Longchuan; McEachern, Donna; Sun, Duxin; Wen, Bo; Luo, Ruijuan; Zhao, Ting; Chinnaiyan, Arul; Asangani, Irfan A.; Stuckey, Jeanne; Meagher, Jennifer Lynn; Ran, Xu; US2015/246923; (2015); A1;,
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. 92933-47-6, name is 5-Isopropyl-1H-pyrazole-3-carboxylic acid, A new synthetic method of this compound is introduced below., Product Details of 92933-47-6

Step5 (3-(6-Chloro-4-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2,5-dihydro-1H-pyrrol-1-yI)(3-isopropyl-1H-pyrazol-5-yI)methanoneTo a stirred solution of 3-isopropyl-IH-pyrazole-5-carboxylic acid (1.1 g, 7.3 mmol) in DMF (20mL) was added DJEA (3.1 g, 24 mmol) and HATU (3.2 g, 8.5 mrnol) and stined at roomtemperature for 10 mm before the addition of 2-chloro-6-(2,5-dihydro- I H-pyrrol-3 -yl)-4-(l – methyl- IH-pyrazol-4-yl)pyridine hydrochloride (1.8 g, 6.1 mmol). The mixture was stirred at room temperature for 2 hrs under a N2 atomsphere. The mixture was diluted with EtOAc (250 mU, washed with H20 (240 mE x 3). The organic phase was dried over anhydrous Na2SO4, filtered andthe filtrate was concentrated and purified by silica gel column chromatography eluting with 0-10% MeOl-I in DCM to give the desired product (1.8 g, 75% yield) as yellow solid. ?H NMR (400 MHz,DMSO-d6) 38.55, 8.50 (2s, IR), 8.22, 8.19 (2s, IH), 7.99, 7.84 (2s, IH), 7.64 (s, IH), 6.91, 6.87 (25, 111), 6.51, 6.50 (2s, 111), 5.06 (m, IH), 4.90 (ni, 111), 4.68 (m, IH), 4.54 (m, lH), 3.93, 3.89 (2s, 3H), 3.01 -2.97 (m, 1H), 1.27- 1.24 (m, 611).

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; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; LAI, Kwong Wah; LIANG, Jun; ZHANG, Birong; LABADIE, Sharada; ORTWINE, Daniel; DRAGOVICH, Peter; KIEFER, James; GEHLING, Victor, S.; HARMANGE, Jean-Christophe; (263 pag.)WO2016/57924; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 5932-27-4, 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. 5932-27-4, name is Ethyl 1H-pyrazole-3-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of ethyl 1H-pyrazole-3-carboxylate (1.4 g, 9.66 mmol), 4-(bromomethyl)- 1,2-difluorobenzene (1.0 g, 4.83 mmol) and potassium hydroxide (0.27 g, 4.83 mmol) in tetrahydrofuran (100 mL) was stirred at 70 °C for 12H. After cooling to RT, the mixture was filtered and the filtrate was concentrated to dryness in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 0 to 100percent) ethyl acetate in petroleum ether) to afford ethyl l -(3,4-difluorobenzyl)-1H-imidazole-4-carboxylate (1.2 g, 93percent yield) as white solid: LCMS (0 to 60percent acetonitrile in water + 0.03percent trifluoroacetic acid over 2 mins) retention timel .25 min, ESI+ found [M+H] = 266.9.

The chemical industry reduces the impact on the environment during synthesis Ethyl 1H-pyrazole-3-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; GENENTECH, INC.; F. HOFFMANN-LA ROCHE AG; PATEL, Snahel; HAMILTON, Gregory; STIVALA, Craig; CHEN, Huifen; ZHAO, Guiling; (1236 pag.)WO2017/4500; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 2458-26-6, name is 3-Phenyl-1H-pyrazole, molecular formula is C9H8N2, 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. SDS of cas: 2458-26-6

Reference Example 1104-Bromo-3-phenyl-1H-pyrazole A solution of 3-phenyl-1H-pyrazole (4.08 g, 28.3 mmol) and NBS (5.04 g, 28.3 mmol) in DMF (40 mL) was stirred for 1 h at room temperature. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was recrystallized from hexane/AcOEt to give the title compound (5.84 g, 93% yield) as a white solid: mp 114-116 C.; NMR (300 MHz, CDCl3): delta ppm 7.39-7.50 (31-1, m), 7.64 (1H, s), 7.77 (2H, d, J=6.8 Hz), 10.73 (1H, brs).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2458-26-6, its application will become more common.

Reference:
Patent; Taniguchi, Takahiko; Kawada, Akira; Kondo, Mitsuyo; Quinn, John F.; Kunitomo, Jun; Yoshikawa, Masato; Fushimi, Makoto; US2010/197651; (2010); 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. 42027-81-6, name is 2-(4-Nitro-1H-pyrazol-1-yl)ethanol, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 42027-81-6

A 100 mL round-bottom flask was charged with a solution of intermediate 28.2 (500 mg, 3.18 mmol, 1.00 equiv) in methanol (20 mL) and palladium on carbon (100 mg). To the above hydrogen gas was introduced. The resulting solution was stirred for 2 h at room temperature. The solids were filtered out and mixture was concentrated under vacuum to provide 350 mg (crude) of intermediate 28.3 as yellow oil. LCMS (ES, m/z): 128 [M+H].

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 42027-81-6.

Reference:
Patent; NIMBUS IRIS, INC.; ROMERO, Donna L.; MASSE, Craig E.; ROBINSON, Shaughnessy; GREENWOOD, Jeremy Robert; HARRIMAN, Geraldine; WO2015/48281; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics