Category: pyrazoles-derivatives

Synthetic Route 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.

Step 1: A clean and dry 500 L glass-lined reactor A was evacuated to -0.08–0.O5MPa and filled with nitrogen to normal pressure. It was repeated for 3 times. The reactors were sampled for oxygen content to ensure it was 3%.[001145j Diisopropylamine (106.0 kg) and 1-methyl-4-iodo-1H-pyrazole (24.3 kg, 23.6 kg corrected) were added to the reactor A at 15-25 C. Cuprous iodide (0.37 kg) was added to reactor A under the protection of nitrogen at 15-25 C. Bis(triphenylphosphine)palladium(II) chloride (1.09 kg) was added to the mixture under the protection of nitrogen at 15-25 C. The mixture was stirred for 20-30 mi Trimethylsilylacetylene (22.2 kg, 14.0 kg corrected) was added to the mixture in portions with 4-5 kg and an interval of 20-30 mm for each portion at 15-30 C. The mixture was allowed to react at 20-30 C. After 2h, the mixture was sampled every 1-2h for purity analysis by HPLC until area% of 1-methyl-4-iodo-1H-pyrazole was 0.5%.[001 146j After reaction completion, the mixture was filtered with a stainless steel centrifuge. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). The filtrate was transferred to reactor A and concentrated under reduced pressure (P -0.08 MPa) at T 45 C until 40-60 L was left. Methyl tert-butyl ether (92.5 kg) was added to the mixture and concentration was continued until 40-60 L was left. Methyl tert-butyl ether (92.2 kg) was added to concentrated mixture and the mixture was sampled for diisopropylamine residual analysis to ensure it was 1%. Active carbon (4.9 kg) was added to the mixture at 15-25 C and the mixture was maintained for 6-8 h under stirring. The mixture was filtered with stainless steel nutsche filter at 15-25 C. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). A solution of citric acid monohydrate (6.1 kg) in purified water (121.6 kg) was added to the filtrate at 15-25 C. The mixture was stirred for 20-30 mm and settled for 20-3 0 mm before separation. The emulsion layer was separated to aqueous phase. The aqueous phase was sampled for pH analysis and wt% analysis to ensure pH was < 7. Active carbon (4.9 kg) was added to the mixture at 15-25 C and the mixture was maintained for 6-8 h under stirring. The mixture was filtered with stainless steel nutsche filter at 15-25 C. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). The filtrate was checked to ensure it was yellow solution. The filtrate was transferred to reactor B and concentrated under reduced pressure (P -0.O8MPa) at T 35 C until 30-40 L was left. Anhydrous ethanol (96.3 kg) was added to the mixture and concentration was continued at T 45 C until 30-40 L was left. The mixture was sampled for methyl tert-butyl ether residual analysis to ensure it was 0.5%. The mixture was cooled to 15-25 C. Purified water (121.3 kg) was added to the mixture through peristaltic pump at 15-25 C at a reference rate of 25-50 kg/h. Brown yellow solid precipitated. The mixture was allowed to crystallize at 15-25 C. After 2h, the mixture was sampled every 1- 2h for mother liquor wt% analysis until it was 0.5% or the difference between the two samples was 0.3%. The mixture was filtered with a stainless steel nutsche filter. The filter cake was rinsed twice with purified water (12.1 kg x2). The filter cake was swept in the stainless steel nutsche filter. After 12h, the solid was sampled every 6-8h for ethanol residual until it was 1%. The product was packaged in one plastic bag. Product weight12.0 kg, Yield = 52.3%, Purity (HPLC) = 98.9%. 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:
Patent; INFINITY PHARMACEUTICALS, INC.; CRENIER, Louis; LESCARBEAU, Andre; SHARMA, Praveen; GENOV, Daniel G.; (324 pag.)WO2017/48702; (2017); A1;,
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Synthetic Route of 288-13-1, 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 288-13-1 as follows.

General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999% purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98% purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.

According to the analysis of related databases, 288-13-1, the application of this compound in the production field has become more and more popular.

Reference:
Article; Teo, Yong-Chua; Yong, Fui-Fong; Lim, Gina Shiyun; Tetrahedron Letters; vol. 52; 52; (2011); p. 7171 – 7174;,
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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. 13808-62-3, name is 4-Methyl-3-phenyl-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C10H10N2

Part A — alpha,4-Dimethyl-3-phenylpyrazole-1-acetic acid Sodium hydride (50.0 g., 57% in oil, 1.2 mole) was added over 20 minutes to a stirred solution of 4-methyl-3-phenylpyrazole (158 g., 1.0 mole) in THF (1.0 l.) maintained at 10-20 C. Ethyl 2-bromopropionate (235 g., 1.3 mole) was added and the solution stirred for 18 hours, after which time ethanol was added and the solvent was removed by evaporation at reduced pressure. The residue was treated at 90 C. with sodium hydroxide (100 g., 2.5 mole) in 800 ml. 60% aqueous methanol for 30 minutes. After cooling, the solution was extracted with ether (3 * 200 ml.), and the aqueous phase was acidified with concentrated hydrochloric acid to give 148 g. of crude alpha,4-dimethyl-3-phenylpyrazole-1-acetic acid, m.p. 151-162 C. Recrystallization from aqueous methanol gave 111 g. of product, m.p. 168-172 C. The analytical sample was recrystallized from ethyl acetate, m.p. 170-172 C. Analysis: Calc’d for C13 H14 N2 O2: C, 67.81; H, 6.13; N, 12.17. Found: C, 68.32; H, 6.14; N, 12.06.

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 13808-62-3.

Reference:
Patent; The Upjohn Company; US4072498; (1978); A;,
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These common heterocyclic compound, 1001020-13-8, name is (3-Trifluoromethyl-1H-pyrazol-4-yl)methanol, 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. Safety of (3-Trifluoromethyl-1H-pyrazol-4-yl)methanol

b) 3-(trifluoromethyl)-7H-pyrazole-4-carbaldehyde(3-(trifluoromethyl)-7/-/-pyrazol-4-yl)methanol (600 mg, 3.61 mmol) was dissolved in MeCN (5 ml_). MnO2 (785 mg, 9.03 mmol) was added. The reaction mixture was heated at 120 0C for 5 min in the microwave. The reaction mixture was filtered through decalite, washed with MeCN (30 ml_), then concentrated in vacuo and purified by flash column chromatography (silica gel; eluent EtOA?heptane, 1 :1) to give the desired product (200 mg, 1.22 mmol, 34 %). 1 H NMR (400MHz, CD3OD): delta 8.44 (s, 1 H), 9.95 (s, 1 H)

The synthetic route of (3-Trifluoromethyl-1H-pyrazol-4-yl)methanol has been constantly updated, and we look forward to future research findings.

Reference:
Patent; N.V. ORGANON; WO2008/3452; (2008); A1;,
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Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 16034-46-1,Some common heterocyclic compound, 16034-46-1, name is 1-Methyl-1H-pyrazole-5-carboxylic acid, molecular formula is C5H6N2O2, 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 100 mL round bottom flask was charged with a solution of 2-methylpyrazole-3- carboxylic acid (0.2662 g, 2.1107 mmol), EDC HCL (0.5634 g, 2.8782 mmol) and HOBt (0.389 g, 2.8782 mmol) in DMF (5 mL) and the reaction mixture stirred for 5 min at rt then N,N-diisopropylethylamine (0.7440 g, 5.7565 mmol) was added and the mixture stirred for 5 min. Then was added a solution of tert-butyl 5-[[3-(3-aminophenyl)-1,2,4-thiadiazol-5-yl]-tert- butoxycarbonyl-amino]-4-chloro-indazole-1-carboxylate (1.042 g, 1.9188 mmol) in DMF (5mL) and the solution stirred at room temperature for 24 h. Then, solvents were removed under vacuum and the resulting residue was purified by silica gel chromatography (40 g column, HP 15-40 uM 60 A flash cartridge from Silicycle) eluting with 0 to 50% hexanes/EtOAc to yield the title compound (0.717 g, 57.386% yield) as a light yellow foam.

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

Reference:
Patent; LYCERA CORPORATION; AICHER, Thomas, D.; PADILLA, Fernando; SKALITZKY, Donald, J.; TOOGOOD, Peter, L.; VANHUIS, Chad, A.; (172 pag.)WO2018/39539; (2018); A1;,
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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. 1369959-12-5, name is 3-Chloro-5-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., Computed Properties of C3H2ClN3O2

Tin (II) chloride (12.8 g, 68 mmol) was added in portions to a solution of 3-chloro-5-nitro- lH-pyrazole (2.0 g, 13.6 mmol) in methanol (200 mL) and cone. HCl (10 mL) at 0 C. The reaction mixture was stirred at room temperature for 6 hours, and the organic solvent was removed under reduced pressure. The residue was diluted with water (20 mL), neutralized to pH 7 with Na2C03, then extracted with EtOAc (3 x 50 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the title compound (1.4 g, 87%), which was used without further purification. 1H NMR (400 MHz, DMSO-d6): delta 11.55 (bs, 1H), 5.26 (s, 2H), 5.21 (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; CORNELL UNIVERSITY; DANA-FARBER CANCER INSTITUTE, INC.; CHILDREN’S MEDICAL CENTER CORPORATION; MELNICK, Ari, M.; GABAS, Lorena, Fontan; US, Ilkay; CASALENA, Gabriella; GRAY, Nathanael, S.; SCOTT, David, A.; HATCHER, John; DU, Guangyan; WU, Hao; QIAO, Qi; (157 pag.)WO2018/85247; (2018); A1;,
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Application of 31108-57-3, 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.

Intermediate 4: 3,5-dibromo-lH-pyrazole-4-carbonitrile To lH-pyrazole-4-carbonitrile (6.76 g, 52.2 mmol) purchased from Aldrich (catalog number CDS008901) were added ethanol (150 mL) and water (225 mL). Then sodium acetate (29.1 g, 355 mmol) was added and the mixture was stirred until solids completely dissolved. Then bromine (10.75 mL, 209 mmol) was added dropwise. After 2 hours the reaction was complete. The reaction was diluted with water then extracted with DCM (3X150ml). The combined organic phases were washed with a saturated aqueous solution of sodilum thiosulfate (Na2S203). Poor layer seperation was observed in separating funnel, so water was added until DCM layer was in the bottom. The organic phase was then dired over MgS04, filtered and concentrated to form a solid. Purification: the solid was first dissolved in EtOAc. When the entire solid was dissolved, additional EtOAc was added to almost double the starting volume. Then hexane was added until solution turned slightly cloudy. After 30 min decantation, the small amount of precipitate formed in the flask was filtered, a dark brown oil left on the filter. The much lighter amber color solution that filtered though was then concentrated and contained mostly the desired product of 3,5-dibromo-lH-pyrazole-4-carbonitrile (8.9 g, 35.5 mmol, 68.0 % yield), it was used without further purification. No proton in the structure (only NH), no NMR spectrum. LCMS: the compound does not ionize.

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

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; NEW YORK UNIVERSITY SCHOOL OF MEDICINE; ALONSO PADILLA, Julio; CHARNLEY, Adam Kenneth; COTILLO TORREJON, Ignacio; ELBAN, Mark; HUGHES, Terry Vincent; KESSLER, Albane Marie; KNAPP-REED, Beth Anne; LIAN, Yiqian; MARTIN, Jose Julio; PENA URQUIZA, Imanol; RODRIGUEZ FERNANDEZ, Ana; (37 pag.)WO2016/55607; (2016); A1;,
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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. 52867-42-2, name is Methyl 2-methyl-5-oxo-2,5-dihydro-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: Methyl 2-methyl-5-oxo-2,5-dihydro-1H-pyrazole-3-carboxylate

c) 5-[3-Butyl-5-(l,2-dihydroxy-2-phenyl-ethyl)-isoxazol-4-ylmethoxy]-2-methyl-2H-pyrazole-3- carboxylic acid methyl esterTo a stirred solution of 5-hydroxy-2H-pyrazole-3-carboxylic acid methyl ester (937 mg, 6.0 mmol) and [3-butyl-5-([E]-styryl)-isoxazol-4-yl]-methanol (1.54 g, 6.0 mmol) in THF (120 mL) at 5 0C under argon was added triphenylphosphine (2.1 g, 7.8 mmol), then diethyl azodicarboxylate (1.06 g, 6.0 mmol) was added dropwise. The reaction mixture was warmed to room temperature overnight. The reaction mixture was then poured into aqueous sodium chloride (saturated) and the mixture was extracted with ethyl acetate. The combined organic layers were then washed with water and saturated sodium hydrogen carbonate solution and then dried over sodium sulfate, filtered and evaporated. Concentration and purification by chromatography (silica, heptane:ethyl acetate = 4:1 to 7:3) afforded the intermediate product (1.07 g, 45%) as a yellow oil. MS: m/e = 396.2 [M+H]+. To a solution of the intermediate product (0.79 g, 2.0 mmol) in tert-butanol (50 mL) was added AD Mix-alpha (2.8 g) with water (50 mL). The reaction mixture was stirred at room temperature overnight and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and concentrated to a yellow oil. The crude material was purified by flash chromatography (silica gel, heptane:ethyl acetate 7:3 to 1 :1) to afford the title compound (440 mg, 51%) as a colorless oil. MS: m/e = 430.2 [M+H]+.

The synthetic route of 52867-42-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; JAKOB-ROETNE, Roland; LUCAS, Matthew, C.; THOMAS, Andrew; WO2010/127975; (2010); A1;,
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These common heterocyclic compound, 151521-41-4, name is 4-Propyl-1H-pyrazol-3-amine, 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. Recommanded Product: 151521-41-4

(A) In the same manner as described in the step (B) of Reference Example 11, 4.5 g of N-(4-n-propyl-1H-pyrazol-3-yl)acetamidoxime was obtained from 7.2 g of 3-amino-4-n-propyl-1H-pyrazole and 9.3 g of triethyl orthoacetate.

The synthetic route of 4-Propyl-1H-pyrazol-3-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Yamanouchi Pharmaceutical Co., Ltd.; US5475114; (1995); A;,
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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. 116008-52-7, name is 4-Amino-1H-pyrazole-3-carboxylic acid, A new synthetic method of this compound is introduced below., COA of Formula: C4H5N3O2

EXAMPLE 125 Trans-3-(naphth-2-yl)-but-2-enoic acid-N-(3-carboxy-1H-pyrazol-4-yl)-amide Prepared analogously to Example 31 from trans-3-(naphth-2-yl)-but-2-enoic acid chloride and 4-amino-1H-pyrazol-3-carboxylic acid in dimethylformamide with the addition of pyridine.

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; Boehringer Ingelheim Pharma KG; US6362210; (2002); B1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics