Day: July 20, 2021

Adding a certain compound to certain chemical reactions, such as: 84547-86-4, name is 4-Bromo-1-methyl-1H-pyrazole-3-carboxylic acid, 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 84547-86-4, name: 4-Bromo-1-methyl-1H-pyrazole-3-carboxylic acid

Example 39 4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-methyl-1H-pyrazole-3-carboxamide A mixture of 4-bromo-1-methyl-1H-pyrazole-3-carboxylic acid (20.0 mg, 0.0976 mmol), NH4Cl (52.2 mg, 0.976 mmol), TBTU (62.6 mg, 0.195 mmol), DIPEA (0.0340 mL, 0.195 mmol) and DMF (2 mL, 20 mmol) was stirred at rt for 10 min. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3*) to remove carboxylic acid starting material. The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15.0 mg, 0.0348 mmol), (1,1’bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.57 mg, 0.00488 mmol), K2CO3 (20.2 mg, 0.146 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95 C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): delta=1.80 (d, J=7.1 Hz, 3H), 3.70 (br. s., 3H), 3.96 (s, 3H), 5.14 (q, J=7.2 Hz, 1H), 6.88 (dd, J=9.2, 4.2 Hz, 1H), 7.05 (t, J=8.8 Hz, 1H), 7.30 (d, J=1.0 Hz, 1H), 7.66 (s, 1H), 7.72 (s, 1H), 8.22 (br. s., 1H). MS (ES+): m/z=428.11/430.12 (100/50) [MH+]. HPLC: tR=1.33 min (polar-3 min, UPLC-ACQUITY).

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

Reference:
Patent; OSI Pharmaceuticals, LLC; US2011/281888; (2011); 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. 81945-73-5, name is 1H-Pyrazol-1-ol, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 81945-73-5

1-Benzyloxy-lH-pyrazole; To a mixture of pyrazol-1-ol (1 g, 11.9 mmol) and /-Pr2NEt (2.02 mL, 11.9 mL) in DCM (15 mL) at 0 0C was added BnBr (4.09 mL, 23.8 mmol). The mixture was allowed to warm up to r.t. and stirred at this temperature for 22 h. The mixture was concentrated in vacuo to afford a yellow paste. The crude product was purified by flash chromatography (silica gel, hexanes/DCM/Et2O (100:0:0 to 80:10:10), Rf 0.23 in hexanes/DCM/Et2O (34:3:3)) to provide the title product as a yellow oil (1.17 g, 56%).

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 81945-73-5.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2006/108591; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 398491-61-7, name is tert-Butyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-5(1H,4H,6H)-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. category: pyrazoles-derivatives

Example 2: 3-[(2-chlorothieno[3,2-d]pyrimidin-4-yl)amino]-6,6-dimethyl-Lambda/-[trans-2- phenylcyclopropyl]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1W)-carboxamide.2a 2Preparation of Compound 2a: rert-butyl-3-[(2-chlorothieno[3,2-cdpyrimidin-4-yl)amino]-6,6- dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate.; To a stirring solution of ferf-butyl 3-amino-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1/7)- carboxylate (2.4g, 9.5 mmol) in DMA (1OmL) was added 2,4-dichlorothieno[3,2-c/]pyrimidine(2.05g, 1.05eq) and triethylamine (2.64ml, 2eq). The resulting mixture was heated to 1500C for 5 minutes in microwave reactor. Saturated NaHCO3 was added and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated in vacuo. The residue was washed with methylene chloride. Compound 2a (2.71 g, 68%) was obtained as a brown solid and directly carried onto the next without further purification. LCMS (API-ES, M+H+): 421. To a stirring mixture of compound 2a(0.102g, 0.24mmol) in CH2CI2 (2ml), was added TFA (2ml). The resulting mixture was stirred at room temperature for 2h. After the reaction mixture was concentrated in vacuo, a solution of TEA (135ul, 4eq) in MeCN (1ml) CH2CI2 (1ml) was added and followed by trans-2- phenylcyclopropyl isocyanate. The resulting mixture was stirred at room temperature for 1h. The reaction mixture was purified by prep-HPLC to provide compound 2 as a white solid (0.021 g, 18%). 1H NMR (CD3OD) delta: 1.04 – 1.12 (m, 2 H), 1.69 (d, J=3.28 Hz, 2 H), 1.95 (m, 1 H), 2.67 – 2.73 (m, 1 H), 4.48 (s, 2 H), 7.01 – 7.06 (m, 3 H), 7.11 – 7.17 (m, 2 H), 7.25 (d, J=5.31 Hz, 1 H), 8.05 (d, J=4.55 Hz, 1 H). Anal. (C^H^NyOSCI.OLambdaHOAc.O^HaO) C, H, N. HPLC: >95% purity.

The synthetic route of tert-Butyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-5(1H,4H,6H)-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; WO2006/72831; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 110860-60-1, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 110860-60-1, name is Methyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

(11) Synthesis of azo pigment (2a) 9.2 g of the intermediate (b) is dissolved in a mixed solution of 55 mL of acetic acid and 37 mL of propionic acid at room temperature. The mixture is cooled with ice to an internal temperature of -3C, and a 40% by weight solution of nitrosylsulfuric acid in sulfuric acid is dropwise added thereto at an internal temperature of from -3C to 4C in 10 minutes. After stirring for 1 hour at an internal temperature of 4C, 0.2 g of urea is added thereto, followed by cooling to an internal temperature of -3C and further stirring for 10 minutes to obtain a diazonium salt solution. Separately, 10 g of the intermediate (d’) is completely dissolved in 150 mL of acetone, and cooled to an internal temperature of 17C, and then added to the above-described diazonium salt solution in 25 minutes at an internal temperature in the range of from-3C to 3C. After completion of the addition, the reaction solution is stirred for 30 minutes at 3C, and the ice bath is removed to allow the internal temperature to rise to room temperature. After stirring the reaction solution at room temperature for 30 minutes, precipitated crystals are collected by filtration, spray washed with 150 mL of acetone, then further spray washed with 100 mL of water. Crystals thus-obtained are suspended in 400 mL of water without drying, and an 8N potassium hydroxide aqueous solution is added thereto to adjust the pH to 5.7. After stirring at room temperature for 20 minutes, resulting crystals are collected by filtration, sufficiently spray washed with water, and then spray washed with 80 mL of acetone. The thus-obtained crystals are dried at room temperature for 12 hours. The thus-obtained crystals are suspended in 580 mL of acetone, and then the mixture is stirred for 30 minutes under reflux. Thereafter, the mixture is cooled to room temperature in 10 minutes, and formed crystals are collected by filtration, and dried at room temperature for 5 hours to obtain 17.1 g of the azo pigment (2a). Yield: 88.5%. Visual observation of the thus-obtained azo pigment (2a) under a transmission microscope (manufactured by JEOL Ltd.; JEM-1010 electron microscope) reveals that the length of the long axis of primary particles is about 15 mum. When X-ray diffraction of the azo pigment (2a) is measured under the aforesaid conditions, characteristic X-ray peaks are shown at Bragg angles (2theta+/-0.2) of 7.6 and 25.6. The X-ray diffraction pattern with characteristic Cu Kalpha line is shown in Fig. 1.

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, Methyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FUJIFILM Corporation; EP2474575; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 3112-31-0, These common heterocyclic compound, 3112-31-0, name is 1H-Pyrazole-3,5-dicarboxylic acid, 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.

Step 1 To a solution of Compound 1 (60 g, 345 mmol) in methanol (600 mL), under nitrogen atmosphere, thionyl chloride (75 mL, 1034 mmol) was added at 0C, followed by heating at reflux for 4 hours. The reaction solution was concentrated in vacuo to yield crude product 2 (64.3 g). LC/MS (Method A): 0.93 min, [M+H]+ = 185.

Statistics shows that 1H-Pyrazole-3,5-dicarboxylic acid is playing an increasingly important role. we look forward to future research findings about 3112-31-0.

Reference:
Patent; Shionogi&Co., Ltd.; EP2327704; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 85290-80-8, name is Ethyl 1-methyl-1H-pyrazole-4-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 85290-80-8, Application In Synthesis of Ethyl 1-methyl-1H-pyrazole-4-carboxylate

Step 2 Preparation of 1-methyl-1H-pyrazole-4-carboxylic acid A solution of 1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (300 mg, 1.95 mmol) in ethanol cooled to 0 C. was treated with a 1N aqueous sodium hydroxide solution. The reaction was then warmed to 25 C. and was stirred at 25 C. for 18 h. At this time, the reaction was concentrated in vacuo and acidified to pH=2 with a 1N aqueous hydrochloric acid solution. This solution was extracted with ethyl acetate (3*50 mL). The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and dried in vacuo to afford 1-methyl-1H-pyrazole-4-carboxylic acid (193 mg, 78.5%) as a white solid: LR-MS for C5H6N2O2 (M-H)+ at m/z=125.

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

Reference:
Patent; Dunten, Peter W.; Foley, Louise H.; Huby, Nicholas J.S.; Pietranico-Cole, Sherrie L.; Yun, Weiya; US2004/14766; (2004); 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. 5744-59-2, name is 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid, A new synthetic method of this compound is introduced below., Quality Control of 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid

Compounds 41-70 were part of a parallel set prepared in library plate format according to General Procedure L, outlined below. ; L. General Procedure for Plate Preparation-Amide Formation XXI: Resin bound deprotected biarylphenol XVII (prepared from intermediate XII, boronates XIVd and XIVe, following general procedures D-F) was distributed into a 96 well plate, 10 mg of resin (0.013 mmol) per well. To the resin 400 mul of dichloromethane was added, followed by 100 mul of DIEA, followed by 0.13 mmol (10 equiv) of heterocyclic carboxylic acid XXa-XXn was added followed by 61 mg (0.13 mmol, 10 equiv) of PyBrop. The plate was shaken at room temperature for 24 hours, then drained and washed with dichloromethane, methanol/dichloromethane, dimethylformamide, methanol/dichloromethane and dichloromethane. The compounds were cleaved with TFA/dichloromethane (600 mul, 1:1) into a 96 deep well plate and submitted for testing without further purification. (Mass spec results obtained are shown in Table 4). Carboxylic Acids Het-COOH XX:

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; Adolor Corporation; US2006/74086; (2006); 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. 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., name: 3-Methyl-4-nitro-1H-pyrazole

Procedure B:General Procedure for the Synthesis of 4-Amino-3 -methyl- 1-N-alkylated pyrazolesA solution of 3-methylpyrazole (1.96mL, 24.0mmol) in sulfuric acid (15mL) was cooled to – 5C and potassium nitrate (l . leq) was added portion-wise. The reaction was warmed to rt and stirred for 16h. The mixture was cooled to 0C and neutralized with ammonium hydroxide solution. The resulting solid was filtered and air-dried to give 3-methyl-4-nitro- 1H-pyrazole. To a solution of 3-methyl-4-nitropyrazole (300mg, 2.6mmol), potassium carbonate (2eq) and the alkylating reagent (l. leq) in acetonitrile (lOmL) was heated at 60C for 18h. After cooling to rt the mixture was diluted with EtOAc and washed with water. The organic phase was collected, dried (MgSC^) and concentrated in vacuo. The crude residue was dissolved in methanol (lOmL), palladium on carbon (50mg) was added and the reaction was stirred under a balloon of hydrogen for 18h. The resulting mixture was filtered through Celite and the filtrate concentrated in vacuo to give the desired product.Example 23: 2-((6-(l-(2-methoxyethyl)-3 -methyl- 1 H-pyrazo 1-4-ylamino)- 1 H-pyrazo lo [3,4- d]pyrimidin- 1 -yl)methyl)benzonitrileThe following compound was made according to the procedure in Example 1, using l-(2- methoxyethyl)-3 -methyl- lH-pyrazo 1-4-amine. 1 -(2 -methoxyethyl)-3 -methyl- lH-pyrazo 1-4- amine was prepared by Procedure B using l-bromo-2-methoxyethane as alkylating agent:1H NMR (d6-DMSO) delta 9.29-9.36 (m, 1Eta), 8.94 (s, 1Eta), 8.09 (s, 1Eta), 7.89 (d, 1Eta), 7.65 (td, 1Eta), 7.51 (t, 1Eta), 7.28-7.30 (m, 1Eta), 5.68 (s, 2Eta), 4.15 (t, 2Eta), 3.63 (t, 2Eta), 3.18 (s, 3Eta), 2.14 (s, 3H); LC-MS method B, (ES+) 389.1, RT = 7.86min

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; CELLZOME LIMITED; RAMSDEN, Nigel; HARRISON, Richard John; OXENFORD, Sally; BELL, Kathryn; PITON, Nelly; DAGOSTIN, Claudio; BOUSSARD, Cyrille; RATCLIFFE, Andrew; WO2011/48082; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 83-10-3, name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, molecular formula is C12H12N2O3, 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: 83-10-3

Step 4) 4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,5-difluorophenoxy)picolinamide To a solution of 4-(4-amino-2,5-difluorophenoxy)picolinamide (200 mg, 0.76 mmol), and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (165 mg, 0.75 mmol) in DCM (10 mL) was added EDCI (175 mg, 0.93 mmol), and HOAT (26 mg, 0.15 mmol). The reaction was stirred at 45 C. for 16 hours, cooled to rt and diluted with EtOAc (20 mL). The solid was collected through filtration, dried at 45 C. in vacuo overnight to give the title compound as a white solid (230 mg, 63.7%). MS (ESI, pos. ion) m/z: 480.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6): delta (ppm) 11.24 (s,1H), 8.53-8.57 (m, 2H), 8.15 (s, 1H), 7.75 (s, 1H), 7.53-7.59 (m, 4H), 7.44-7.45 (m, 3H), 7.24-7.25 (d, J=5.2 Hz, 1H), 3.43 (s, 3H), 2.70 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 83-10-3, its application will become more common.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; Calitor Sciences, LLC; Xi, Ning; Wu, Yanjun; Liao, Min; Feng, Yanming; US2015/37280; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 1310350-99-2, name is 4-Chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid, 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 4-Chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid

4-Chloro-l -(difluoromethyl)- 1 H-pyrazole-3 -carboxylic acid (0.083 g, 0.423 mmol) was added to DMTMM (0.117 g, 0.423 mmol) in MeOH (2 mL). After stirring the mixture for 5 minutes, a solution of intermediate 1-12 (0.1 g, 0.384 mmol) in MeOH (2 mL) was added at 0 C, and the mixture was stirred for 24 hours. The solvent was evaporated in vacuo. The residue was then suspended in DCM and treated with sat. aq. Na2C03 sol. The organic layer was separated, dried (MgS04), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 7 M ammonia in MeOH/DCM 0/100 to 5/95). The desired fractions were collected and concentrated in vacuo. The product was purified further by preparative HPLC (RP, C18 XBridge 30×100 5 urn), mobile phase (gradient 90% 0.1% to 0% 0.1% NH4HCO3/NH4OH pH 9 solution in water, 10% MeCN). The desired fractions were collected and the product was extracted with DCM. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The residue was dried overnight (vacuum oven, 50C) yielding compound 5 (53 mg, 31% yield) as a pale yellow solid.

The synthetic route of 4-Chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; OEHLRICH, Daniel; GIJSEN, Henricus, Jacobus, Maria; WO2014/198854; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics