Tag: M.W:200-300

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. 706819-66-1, name is 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone, A new synthetic method of this compound is introduced below., Safety of 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone

General procedure: A 40 mL vial was charged with 5e (640 mg, 1.61 mmol), 12 (546 mg, 1.77 mmol), anhydrous MeCN (15mL) and -325 mesh K2CO3 powder (266 mg, 1.93 mmol). The mixture was stirred at 20 C for 18 h, before being diluted with EtOAc (15 mL) and H2O (15 mL). The phases were separated and the aqueous phase was extracted with additional EtOAc (2 x 10mL). The combined extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica (heptane – EtOAc) to afford 520 mg (52%) of 15d and 410 mg (41%) of 16d.

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:
Article; Wright, Stephen W.; Arnold, Eric P.; Yang, Xiaojing; Tetrahedron Letters; vol. 59; 4; (2018); p. 402 – 405;,
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. 1202993-11-0, name is 5-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Product Details of 1202993-11-0

Step 2 : preparation of of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride (lllb-1 ) 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid and 44.3 ml of thionyl chloride are refluxed for 5 hours. After cooling down, the reaction mixture is evaporated under vacuum to yield 3.5 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride as a yellow oil. H NMR (400 MHz, CHCI3-c/6) delta ppm : 3.97 (s, 3H); 7.00 (t, J = 52.01 Hz, 1 H); IR (TQ) : 1759 and 1725 cm”1 (C=0).

The synthetic route of 1202993-11-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER CROPSCIENCE AG; BENTING, Juergen; COQUERON, Pierre-Yves; CRISTAU, Pierre; DAHMEN, Peter; DESBORDES, Philippe; GARY, Stephanie; GREUL, Joerg; HADANO, Hiroyuki; MEISSNER, Ruth; WACHENDORFF-NEUMANN, Ulrike; WO2011/151370; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 139308-52-4, The chemical industry reduces the impact on the environment during synthesis 139308-52-4, name is Ethyl 3-bromo-1-methyl-1H-pyrazole-4-carboxylate, I believe this compound will play a more active role in future production and life.

(4-(((Trans)-4-morpholinocyclohexyl)amino)quinazolin-6-yl)boronic acid (30 mg, 0.084mmol) was dissolved in EtOH (1 mL) and added to a vial containing ethyl 3-bromo-1-methyl-1H-pyrazole-4-carboxylate (29.0 mg, 0.126 mmol) and Si-DPP-Pd (64.8 mg, 0.0 17mmol). Potassium carbonate (1M in water, 0.084 ml, 0.168 mmol) was added, the vial wassealed and the resulting mixture was then heated to 125 C for 10 minutes under microwave irradiation. The mixture was filtered and purified by mass triggered reverse phase HPLC (ACN/water with 0.1% TFA modifier) to afford the title product as a TFA salt. MS: 465 (M+1). ?H NMR (DMSO-d6, 600 MHz) oe 9.79 (s, 1H), 8.89 (s, 1H), 8.75 (s, 1H), 8.48 (s,1H), 8.25 (d, J = 8.69 Hz, 1H), 7.81 (d, J = 8.67 Hz, 1H), 4.39 (br s, 1H), 4.14 (q, J = 7.10 Hz, 2H), 4.02-4.00 (m, 2H), 3.95 (s, 3H), 3.71-3.69 (m, 2H), 3.44-3.39 (br s, 1H), 2.52-2.50 (m, 4H), 2.20-2.18 (m, 2H), 2.10-2.08 (m, 2H), 1.64-1.58 (m, 4H), 1.16 (t,J= 7.10 Hz, 3H).

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; ALTMAN, Michael, D.; ANDRESEN, Brian, M.; BRUBAKER, Jason, D.; CHILDERS, Matthew, L.; DONOFRIO, Anthony; FISCHMANN, Thierry; GIBEAU, Craig, R.; KATTAR, Solomon, D.; LESBURG, Charles, A.; LIM, Jongwon; MACLEAN, John, K. F.; MANSOOR, Umar, F.; NORTHRUP, Alan, B.; SANDERS, John, M.; SMITH, Graham, F.; TORRES, Luis; (91 pag.)WO2016/53771; (2016); 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. 1227611-94-0, name is 4-(4-Iodo-1H-pyrazol-1-yl)cyclohexanone, This compound has unique chemical properties. The synthetic route is as follows., Formula: C9H11IN2O

Intermediate 21 and 22: cis and trans-4-(4-Iodo-pyrazol-1-yI)-cyclohexanol Sodium borohydride (86 mg; 2.27 mmol; 0.5 eq.) was added portionwise to a suspension of 4-(4-lodo-pyrazol-1-yl)-cyclohexanone (1.33 g; 4.55 mmol; 1.0 eq.) in EtOH (10 mL).The reaction mixture was stirred at RT for 30 mm and concentrated under vacuum. The residue was taken up with EtOAc (50 mL) and washed with NH4CI aq sat (50 mL). The aqueous phase was back-extracted with EtOAc (twice). Combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to give 1.42 g of an oil. Purification by flash chromatography on silica (heptane/EtOAc, gradient from 80:20 to 40:60) afforded the title compounds.1st eluting compound: colorless glue (234 mg, 18%). Cis-4-(4-Iodo-pyrazol-1-yl)-cyclohexanol. HPLC (Condition A): Rt 2.69 mm (purity 99.7 %). MS (ESI+): 293.1.2nd eluting compound: white powder (730 mg, 55%). Trans-4-(4-lodo-pyrazol-1-yl)-cyclohexanol. HPLC (Condition A): Rt2.65 mm (purity 100 %). MS (ESI+): 293.1.

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 1227611-94-0.

Reference:
Patent; ARES TRADING S.A.; CROSIGNANI, Stefano; JORAND-LEBRUN, Catherine; GERBER, Patrick; MUZERELLE, Mathilde; WO2014/8992; (2014); 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

Application of 330792-70-6, 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. 330792-70-6 name is 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile, 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.

[0553] To a solution of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (83 mg, 0.3mmol) in HOAc (2 mL) was added sodium 2-nitro-1,3-dioxopropan-2-ide (47 mg, 0.3 mmol).After stirring at RT for 1 hr, water (2 mL) was added. The mixture was partitioned between EA(25 mL) and brine (25 mL). The combined organic layers were washed with brine (25 mL x 2),dried over Na2S04 and concentrated to afford 90 mg of 6-nitro-2-(4-phenoxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (84percent) as a yellow solid. MS (ESI) m/e[M+1t 358.2.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; GUO, Yunhang; BEIGENE, LTD.; WANG, Zhiwei; WO2014/173289; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3528-45-8,Some common heterocyclic compound, 3528-45-8, name is 1-(4-Methoxybenzyl)-1H-pyrazol-5-amine, molecular formula is C11H13N3O, 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.

1-(4-Methoxybenzyl)-1H-pyrazol-5-amine (3.94 g, 1 9.39 mmol), followed by diethyl 2-(ethoxymethylene)malonate (4 mL, 20 mmol) was added to a 200 mL round bottom flask fitted with a distillation head to remove ethanol. The mixture was heated to 130 C for 45 min, then 10 mL of diphenyl ether was added and the temperature was raised to 240 C for 2 h. The reaction mixture was then cooled to rt and Et2O ( 1 00 mL) was added. The resulting precipitate was collected by vacuum filtration and dried under vacuum to afford the target compound as a white solid (4 g, 62%).

The synthetic route of 3528-45-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GENENTECH,INC.; FORMA TM, LLC; BAIR, Kenneth W.; BAUMEISTER, Timm R.; BUCKMELTER, Alexandre J.; CLODFELTER, Kanl H.; DRAGOVICH, Peter; HAN, Bingsong; LIN, Jian; LIU, Xiongcai; REYNOLDS, Dominic J.; SMITH, Chase C.; WANG, Zhongguo; YUEN, Po-Wai; ZAK, Mark; ZHANG, Yamin; ZHENG, Xiaozhang; ZHAO, Guiling; WO2013/127268; (2013); 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. 37687-24-4, name is Diethyl 3,5-pyrazoledicarboxylate, This compound has unique chemical properties. The synthetic route is as follows., Safety of Diethyl 3,5-pyrazoledicarboxylate

Example 4: ethyl 4-hydroxy-6-methyl-pyrazolo[l,5-a]pyrazine-2-carboxylate (0257) l-Chloropropan-2-one (10.5 kg, 113 mol) was added slowly at room temperature (0258) (exothermic) to a suspension of diethyl lH-pyrazole-3,5-dicarboxylate (20 kg, 94.2 mol) and cesium carbonate (30.7 kg, 94.2 mol) in acetone (200 1). The reaction mixture was stirred for 1.5 hours, filtred and the precipitate was washed with acetone. Acetone was distilled off from the filtrate at 60 C to obain a volume of 60-90 1, DMSO (85 1) was added and the distillation was continued until acetone was completely removed. (0259) Ammonium acetate (14.5 kg, 188 mol) was added at room temperature. The reaction mixture was stirred at 80 C for 18 hours, cooled to 60 C and water (290 1) was slowly added. The suspension was stirred 2 hours at 0-5 C. The precipitate was filtered off, washed with water and dried at 70 C under high vacuum affording ethyl 4-hydroxy-6- methyl-pyrazolo[l,5-a]pyrazine-2-carboxylate (16.8 kg, 80.6%) as beige crystals. (0260) 1H-NMR (600 MHz, DMSO-d6): 11.51 (s, 1H), 7.62 (s, 1H), 7.32 (s, 1H), 4.33 (q, 2H), 2.14 (s, 3H), 1.32 (t, 3H); MS(ISP): m/e = 222.09 (M+H+).

According to the analysis of related databases, 37687-24-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; DOTT, Pascal; FEYEN, Fabian; HILDBRAND, Stefan; HOFFMANN, Ursula; HOFFMANN-EMERY, Fabienne; MEIER, Roland; MOINE, Gerard; REGE, Pankaj; WUITSCHIK, Georg; (64 pag.)WO2017/186668; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 83-10-3, name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-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 83-10-3, Application In Synthesis of 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid

(Step 11) N-(4-(5-bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide; To a solution of 4-(5-bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluoroaniline (57 mg, 0.178 mmol) and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (124 mg, 0.534 mmol) prepared in Preparation Example 1 in dimethylformamide (2 mL), HATU (270 mg, 0.711 mmol) and triethylamine (0.1 mL, 0.711 mmol) were sequentially added and stirred at 50 C. overnight. The resulting reaction mixture was concentrated under reduced pressure and the resulting residue was extracted with dichloromethane and water. The organic layer was separated, dried with magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (10% ethyl acetate in dichloromethane) to give the target compound as a white solid (60 mg, 0.111 mmol, 63% yield).MS (ESI pos. ion) m/z: 536, 538 (MH+). Calc’d exact mass for C25H19Br79FN5O3: 535, Calc’d exact mass for C25H19Br81FN5O3: 537.1H NMR (400 MHz, CDCl3): 10.89 (br s, 1H), 7.91 (dd, J=12.4 Hz, 2.4 Hz, 1H), 7.78 (d, J=5.6 Hz, 1H), 7.65 (d, J=2.8 Hz, 1H), 7.59-7.54 (m, 2H), 7.52-7.46 (m, 1H), 7.38-7.35 (m, 2H), 7.31-7.28 (m, 1H), 7.19 (t, J=8.8 Hz, 1H), 6.80 (d, J=2.8 Hz, 1H), 5.67 (dd, J=5.6 Hz, 1.2 Hz, 1H), 3.38 (s, 3H), 2.80 (s, 3H).

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; NEOPHARM CO., LTD.; US2011/183983; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics