Category: 25016-11-9

Synthetic Route of 25016-11-9, 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 25016-11-9 as follows.

To a solution of l-methyl-IH-pyrazole-4-carbaldehyde (104a)(4.8 g, 43.6 mmol) in tetrahydrofuran (80 mL) was cooled to 0 C was added dropwise (3- (bis(trimethylsilyl)amino)phenyl)rnagnesium chloride (49c) (49.0 mL, 49.0 mmol) and stirred at 0 C for 2 h. The reaction was quenched with saturated aqueous NH4CI (1 20 mL)and extracted with ethyl acetate (2 x 120 rnL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4 followed by filtration and concentration. The residue was dissolved in ether (200 mL), treated with 4 N HCI in I ,4-dioxane (24 mL) and stirred at room temperature for 2 h. The solid obtained was collected by filtration washedwith ether, dried under vacuum to give (3-aminophenyl)(l-methyl-IH-pyrazol-4- yl)methanol (104b) (6.01 g, 68%) as an off-white solid; ?H NMR (300 MHz, DMSO-d(,) 8 7.47 (s, 111), 7.46- 7.20 (in, 5H), 5.69 (s, I H), 3.76 (s, 3H); MS (ES+) 204.1 (M+1).

According to the analysis of related databases, 25016-11-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; KOTIAN, Pravin, L.; BABU, Yarlagadda, S.; WU, Minwan; CHINTAREDDY, Venkat, R.; KUMAR, V., Satish; ZHANG, Weihe; WO2015/134998; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 25016-11-9, These common heterocyclic compound, 25016-11-9, name is 1-Methyl-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.

To a solution of 1-(methylsulfonyl)-5,6-dihydropyridin-2(11])-one (200 mg, 1.14 mmol, 1.0 eq), diethyl phosphorochloridate (197 mg, 1.14 mmol, 1 eq) and 1-methyl-1H-pyrazole-4- carbaldehyde (100 mg, 0.91 mmol, 0.8 eq) in THF (10 mL) at 0C was added LiHIVIDS 1M in THF (2.5 mL, 2.50 mmol, 2.0 eq). The reaction mixture was stirred at 0C for lh. Progress ofreaction was monitored by TLC. Reaction mixture was quenched by saturated ammonium chloride solution 20 mL and extracted with ethyl acetate (3 x 50 mL). Combined organic layer was washed with brine solution (50 mL) and dried over anhydrous Na2SO4. Removal of solvent under reduced pressure gave the crude which was purified by flash column chromatograpy (0-70% EtOAc-hexane) as eluent to 1- { [(E)-2-( 1-methyl- 1H-pyrazol-4-yl)ethenyl] sulfonyl } -5,6-dihydropyridin-2(11])-one (90 mg, 29.50%).LCMS: 268[M+1]1H NMR (400IVIHz, CDC13) (57.69 (s, 1 H), 7.59 (s, 1 H), 7.55 (d, 1 H), 6.91 (d, 1 H), 6.81 -6.86 (m, 1H), 5.97 (d, 1 H), 3.96 (t, 2 H), 3.92 (s, 3 H), 2.51 – 2.57 (m, 2 H),

The synthetic route of 25016-11-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AURANSA INC.; PROTTER, Andrew, Asher; GREEN, Michael, John; CHANG, Hak, Jin; PHAM, Son, Minh; CHAKRAVARTY, Sarvajit; LUEDTKE, Gregory, R.; (254 pag.)WO2019/103897; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, molecular formula is C5H6N2O, 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

Preparation 65: 3 ‘-Chloro-4-( 1 -methyl- 1 H-pyrazol-4-ylmethyl)-3 ,4,5 ,6-tetrahydro-2H- [l,2′]bipyrazineDissolve 3′-chloro-3,4,5,6-tetrahydro-2H-[l,2’]bipyrazinyl (3.43 g, 17.3 mmol) in tetrahydrofuran (100 mL). Add 1 -methyl- lH-pyrazole-4-carbaldehyde (2.244 g, 20.38 mmol) in dry tetrahydrofuran (5 mL), stir for 10 min. at room temperature, add sodium triacetoxyborohydride (4.32 g, 20.4 mmol) and subject the reaction to ultrasound stirring for 6 hr. at room temperature. Add saturated aqueous sodium hydrogen carbonate (100 mL) then 2 N sodium hydroxide (10 mL) to the mixture and extract with DCM (2 x 200 mL). Pass the combined DCM extracts through an 1ST Phase Separator Frit, concentrate and purify (silica gel chromatography, eluting with 0: 100 to 8:92 methanol:DCM), to give the title preparation as a crystalline solid (5.21 g, 92%). MS (ES): m/z = 293.1 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 25016-11-9, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; WO2008/141020; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 25016-11-9, 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. 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows.

Example 12: l-{l-[9-Methyl-8-(l-methyl-lH-pyrazol-4-yI)-9H-purin-6-yI]piperidin-4- yI}-l,3-dihydro-2H-benzimidazol-2-one (Compound 149)l H9-Methy -8-a-methyl-lH-pyrazol-^2H-benzimidazol-2-one[00207] To a solution of l-(l-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)- lH-benzo[d]imidazol-2(3H)-one (70 mg, 0.2 mmol) in anhydrous ethanol (8 mL) were added 1 -methyl- lH-pyrazole-4-carbaldehyde (34 mg, 0.3 mmol) and catalytic amount of hydrochloric acid (0.05 mL, 4M HCl in Dioxane, Aldrich). The reaction mixture was heated to 80 C for 18 hours. The resulting precipitate was collected by vacuum filtration, washed with ethanol (2 mL) and dried under reduced pressure, to give 62.6 mg (70% yield) of the title compound. NMR (400MHz, DMSO-d6): delta 10.84 (s, 1H), 8.41 (s, 1H), 8.25 (s, 1H), 8.02 (s, 1H), 7.13 (dd, 1H), 6.93 (m, 3H), 4.53 (m, 1H), 3.92 (s, 3H), 3.81 (d, 3H), 3.33 (m, 2H), 3.24 (m, 2H), 2.33 (m, 2H), 1.82 (d, 2H); MS (EI) for C22H23N9O: 430.4 (MH+).

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

Reference:
Patent; EXELIXIS, INC.; PATRICK, Kearney; WO2012/37226; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, 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. Recommanded Product: 1-Methyl-1H-pyrazole-4-carbaldehyde

Intermediate 69 (600mg, 1 eq.) was dissolved in tetrahydrofuran, and lithium aluminum hydride (210 mg, 1 eq.) was added under ice bath and the mixture was reacted at room temperature for 2 h. After completion of the reaction, 210 mul of water, 210 mul of 10percent aqueous sodium hydroxide solution, and 630 mul of water were successively added, followed by addition of anhydrous magnesium sulfate. The mixture was stirred for a while, filtered and evaporated to dryness to give 400 mg of an oil. MS (ESI): 113(M+H)

The synthetic route of 25016-11-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Institute Of Materia Medica Chinese Academy of Sciences; SHEN, Jianhua; WANG, Yiping; CHEN, Xinde; XU, Wenwei; WANG, Kai; (84 pag.)EP3239135; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. HPLC of Formula: C5H6N2O

A solution of N3-(3,5-dichlorophenyl)-lH-l,2,4-triazole-3,5-diamine Intermediate 2 (70 mg, 287 muiotaetaomicron) and 1 -methyl- lH-pyrazole-4-carbaldehyde (108.9 mg, 982 muiotaetaomicron) in MeOH (3 ml) was stirred at 45 C for 4 days to give a suspension, cooled to -20 C and was filtered to collect the solid. The solid was re-suspended in MeOH (5 ml), NaBH4 (65.1 mg, 1.72 mmol) was added and the reaction was stirred for 1 hour. The solvent was removed, and the reaction mixture was redissolved in EtOAc (5 ml) and washed with water (2x 4 ml), dried over MgS04 and concentrated in vacuo. Crystallization from DCM/hexanes afforded a white solid as desired product (66.6 mg, 69% yield). MS +m/z: 338 (M+H)+

The synthetic route of 25016-11-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DING, Qingjie; JIANG, Nan; WEIKERT, Robert James; WO2014/135422; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 25016-11-9, 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 25016-11-9 as follows.

Potassium terf-butoxide (23.47 g of 95%, 199.1 mmol, 2.44 equiv.) was suspended in anhydrous DME (90 mL) and cooled to – 60 0C. TosMIC (23.76 g, 121.7 mmol, 1.49 equiv.) was dissolved in anhydrous DME (75 mL), and this was added drop-wise to the potassium terf-butoxide solution over 20 minutes. After stirring for 20 minutes between – 60 and – 55 0C, the compound of formula IX, in anhydrous DME (55 ml_), was added over 23 minutes. The reaction was stirred one hour at – 55 to – 50 0C to yield a thick suspension. Methanol (90 ml_) was then added resulting in a clear brown solution. The cooling bath was removed, and after stirring 5 minutes in air, the reaction flask was immersed in an oil bath preheated to 85 0C. The reaction was stirred for 1 hour. After cooling, the mixture was concentrated and the resulting tan solid was dissolved in water (180 ml_) with acetic acid (9 ml_). This was extracted with ethyl acetate (3 x 250 ml_), and these extracts were combined, washed with saturated aqueous sodium chloride (100 ml_), dried over sodium sulfate, filtered and concentrated to yield a brown oil (13.71 g). This oil was dissolved in dichloromethane and purified by silica-gel chromatography using a gradient from 0% to 15% dichloromethane-acetone to yield the compound of formula Xl as a bright yellow oil (7.89 g, 63% yield).

According to the analysis of related databases, 25016-11-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SCHERING CORPORATION; WO2008/153870; (2008); 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. 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 25016-11-9

To a solution of tert-butyl 2-(diethoxyphosphoryl)acetate (12.60 g, 49.9 mmol) in tetrahydrofuran (THF) (30 mL) was added NaH 60% dispersion in mineral oil (2.179 g, 54.5 mmol) slowly. The mixture was stirred for 10 min at room temperature. A solution of l-methyl-lH-pyrazole-4-carbaldehyde (5.0 g, 45.4 mmol) in tetrahydrofuran (THF) (30 mL) was added slowly. After addition, the reaction mixture was stirred for 20 min at room temperature. The LCMS showed a complete reaction. The mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water and dried over anhydrous MgS04. It was filtered and the filtrate was concentrated to give the crude product which was then purified on the Combiflash column chromatography eluting with a gradient of 0 to 50% ethyl acetate in hexanes. The title compound was obtained as a clear colorless oil (9.0 g, 43.2 mmol, 95 % yield). LC-MS mlz 208.9 (M+H)+, 0.93 min (ret. time).

According to the analysis of related databases, 25016-11-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; ASTEX THERAPEUTICS LIMITED; BUDZIK, Brian W; LI, Peng; PERO, Joseph E.; GRIFFITHS-JONES, Charlotte Mary; HEIGHTMAN, Thomas Daniel; NORTON, David; WILLEMS, Hendrika Maria Gerarda; WOOLFORD, Alison Jo-Anne; (176 pag.)WO2018/109642; (2018); A1;,
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, Product Details of 25016-11-9

To a 22 L 3-neck RB flask in an ambient temperature water bath was charged with 7-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine monosulfate 6 (400 g, 1.38 mol) and sodium acetate (237 g, 2.89 mol) as solids, followed by 5 L MeOH. 1-methyl-1H-pyrazole-4-carbaldehyde (176 g, 1.60 mol) was then added in a single portion. The mixture was stirred for ~1 h, before the addition of sodium cyanoborohydride (143 g, 2.27 mol) in three portions over 15 min. After 2 h, additional sodium cyanoborohydride (13 g) was added, and it was stirred for another 4 h. Sarcosine (19 g, 0.21 mol) was then added and it was stirred at rt overnight. The solution was cooled to ~10 C, before the addition of 8 L water over 0.5 h while cooling in an ice bath. Then 2.5 L of 2N NaOH solution was added over 2.5 h (pH > 12). Additional 1.5 L water was added in a single portion. It was cooled in an ice bath and stirred overnight. The precipitate was collected by filtration, washed with water (2 x 1 L), and dried in vacuum at 50-60 C to afford the title compound (381.7 g, 97%). 1H NMR (500 MHz, d6-DMSO) d ppm 2.49-2.53 (m, 4H), 2.96-2.99 (m, 4H), 3.28 (s, 2H), 3.78 (s, 3H), 7.28 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.95-7.80 (m, 2H).

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

Reference:
Article; Xiong, Hui; Wu, Ye; Lehr, Scott G.; Blackwell, William; Steelman, Gary; Hulsizer, Jim; Urbanek, Rebecca A.; Tetrahedron Letters; vol. 53; 44; (2012); p. 5833 – 5836,4;,
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

1-Methyl-1H-pyrazole-4-carbaldehyde (11.0 g, 0.1 mol), sodium bromate (6.0 g, 0.04 mol) and 50 g of acetic acid (0.83 mol) were mixed at room temperature. Add 12.5 g of ammonia-containing molecular mass concentration of 25% ammonia water and 100 ml of water. heating to 90 C, the reaction is exothermic, maintaining the reaction temperature of 100 C, refluxing reaction for 1 hour (to 1-methyl-1H-pyrazole-4-carbaldehyde reaction is complete), The reaction solution was cooled to room temperature, poured into ice water and quenched and diluted. neutralize until the reaction solution is neutral, extract with ethyl acetate, and dry. After concentrating the product, it is distilled under reduced pressure and recrystallized.The product obtained was 10.2 g, the yield was 95%, and the purity was over 99%.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Changsha Luxing Biological Technology Co., Ltd.; Tan Yongjun; (14 pag.)CN108707113; (2018); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics