Tag: M.W=0-100

Electric Literature of 930-36-9, 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. 930-36-9, name is 1-Methylpyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

The (1 -methyl-1 H-pyrazol-5-yl)acetic acid used in the above procedure was prepared as follows: (i) 1 -Methyl-1 H-pyrazole-5-carbaldehyde was prepared as follows (c.f. Bioorg. Med. Chem., 2001 , 9, 961-982): A solution of 1 -methyl- 1 H-pyrazole (11.0 g, 0.134 mol) in tetrahydrofuran (200 ml) was stirred at -700C under argon. n-Butyl lithium (2.5 M in hexanes, 58.8 ml, 0.147 mol) was added dropwise maintaining the internal reaction temperature below -600C. The mixture was cooled to -700C and N, N- dimethylformamide (40 ml) was added dropwise. The reaction mixture was allowed to warm to room temperature overnight. The mixture was cooled to 00C and water (200 ml) was added followed by ethyl acetate (300 ml). The organic layer was separated and the aqueous layer was re-extracted with ethyl acetate. The combined organic extracts were washed with water, brine, then dried and evaporated. The residue was purified by flash chromatography on silica gel eluting with 0-100% ethyl acetate in hexanes to afford 1 -methyl-1 H-pyrazole-5-carbaldehyde which was used in the next step.

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, 1-Methylpyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/125600; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 132712-71-1, 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. 132712-71-1, name is 3-Methyl-1H-pyrazol-5-ol, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: 5-Amino-4-arylazo-3-methyl-1-phenylpyrazoles (0.01 mol) weredissolved in a mixture of glacial acetic acid and concentrated hydrochloricacid (20 ml, ratio 1:1) and the solutionwas then cooled to 0-5 C. Sodiumnitrite (0.69 g, 0.01 mol) in water (10 ml) was then added to this solution dropwise with vigorous stirring, for about 1 h, while cooling at0-5 C. Then the resulting diazonium solution was added in portionsover 30 min to a vigorously stirred solution of 5-hydroxy-3-methyl-1H-pyrazole or 5-hydroxy-3-methyl-1-phenylpyrazole (0.01 mol) in KOH (0.56 g, 0.01mol) andwater (10ml) between 0 and 5 C,maintainingthe pHat 7-8 by simultaneous sodiumacetate solution addition. The mixture was then stirred for 2 h at 0-5 C. The precipitated product separated upon dilution with water (50 ml) was filtered off, washed with water several times, dried and crystallized from DMF-H2O

The chemical industry reduces the impact on the environment during synthesis 3-Methyl-1H-pyrazol-5-ol. I believe this compound will play a more active role in future production and life.

Reference:
Article; Karci, Fikret; Bakan, Emine; Journal of Molecular Liquids; vol. 206; (2015); p. 309 – 315;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1453-58-3, 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. 1453-58-3 name is 3-Methylpyrazole, 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.

Potassium /-butoxide (3.9 g, 0.33 mmol) was dissolved in DMSO (25 mL). To this solution was added 3 -methyl pyrazole (2.7 g, 0.33 mmol) and the reaction was heated at 50 °C for 30 min. l-Bromo-4-chloro-2-fluorobenzene (4.6 g, 0.22 mmol) was then added and the reaction was stirred at 50 °C for 16 h. The reaction was cooled to RT and extracted with water and EtOAc, washed with brine, and dried over Na2S04) filtered and concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtO Ac/heptane) provided l-(2- bromo-5-chlorophenyl)-3-methyl-lH-pyrazole and l-(2-bromo-5-chloroplienyl)-5-methyl-lH- pyrazole as a 4: 1 mixture that was used in the next step directly,

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

Reference:
Patent; KAROS PHARMACEUTICALS, INC.; DE LOMBAERT, Stephane; GOLDBERG, Daniel R.; BRAMELD, Kenneth; SJOGREN, Eric Brian; SCRIBNER, Andrew; WO2015/35113; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 1192-21-8, 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. 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

BrettPhos 3rd generation precatalyst (12.44 mg, 0.02 mmol) was added to CS2CO3 (304 mg, 0.93 mmol), 1 -methyl- lH-pyrazol-5-amine (91 mg, 0.93 mmol) and (5)-2-(2-chloro-5- methylpyrimidin-4-yl)-7-(3-(difluoromethyl)benzyl)-6-methyl-6,7-dihydroimidazo[l,2- a]pyrazin-8(5H)-one (Intermediate 69; 130mg, 0.31 mmol) in 1,4-dioxane (5 mL) under nitrogen. The resulting mixture was stirred at 100 °C for 4 hours. The solvent was then removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 6percent MeOH in DCM. Pure fractions were evaporated to dryness to afford a residue. This residue was purified further by preparative HPLC (XSelect CSH Prep C18 OBD column, 5mu silica, 19 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1percent Formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (5)-7-(3- (difluoromethyl)benzyl)-6-methyl-2-(5-methyl-2-((l-methyl-lH-pyrazol-5- yl)amino)pyrimidin-4-yl)-6,7-dihydroimidazo[l,2-a]pyrazin-8(5H)-one (Example 21; 85 mg, 57.1percent) as a white solid. lH NMR (300 MHz, DMSO, 23 °C) delta 1.12 (3H, s), 2.40 (3H, s), 3.70 (3H, s), 3.90-4.10 (1H, m), 4.36-4.44 (3H, m), 5.14 (1H, d), 6.29 (1H, d), 7.04 (1H, t), 7.33 (1H, d), 7.50-7.59 (4H, m), 7.93 (1H, s), 8.32 (1H, s), 9.21 (1H, s). m/z (ES+), [M+H]+ = 479.

The synthetic route of 1-Methyl-1H-pyrazol-5-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; WARD, Richard, Andrew; JONES, Clifford, David; SWALLOW, Steven; GRAHAM, Mark, Andrew; DOBSON, Andrew, Hornby; MCCABE, James, Francis; (223 pag.)WO2017/80979; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3920-50-1,Some common heterocyclic compound, 3920-50-1, name is Pyrazole-3-carboxaldehyde, molecular formula is C4H4N2O, 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.

Reference Production Example 6-1 1-(hydroxymethyl)-3-formyl-1H-pyrazole The mixture of 0.96 g of 3-formyl-1H-pyrazole, 0. 60 g of paraformaldehyde and 0.3 ml of triethylamine was stirred at 100 °C for 5 hours. After the reaction mixture was cooled to room temperature, acetone was added to the reaction mixture. The mixture was filtered. The filterate was concentrated under reduced pressure to obtain 1.21 g of 1-(hydroxymethyl)-3-formyl-1H-pyrazole. The crude product was used for next process without purification. 1H-NMR(CDCl3,TMS,delta(ppm)):5.63(2H,s),6.84(1H,d),7.67(1H,d),9.96(1H,s)

The synthetic route of 3920-50-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sumitomo Chemical Company, Limited; EP1710234; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 930-36-9, These common heterocyclic compound, 930-36-9, name is 1-Methylpyrazole, 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.

Under room temperature, the 1-methyl -1H-pyrazole (2.0g, 24.4 mmol) dissolved in THF in (30 ml). Under the protection of the nitrogen of the obtained mixture to lower the temperature to -78 C, then slowly dripping n-BuLi to the (10.72 ml, 26.8 mmol). Then the resulting mixture at -78 C stirring 2 hours, to room temperature, then the stirring is performed for 1 hour. Then to the reaction solution to maintain this temperature in drying CO2gas, approximately through 5 minutes. After stirring at room temperature, to 1 hours. To the obtained water is added in the mixture of (30 ml) the reaction quenching and diluting. The resulting mixture is extracted with methylene chloride. After acid aqueous phase precipitating a large amount of solid, filtered. The resulting filter cake is dried to obtain 1.5 g of white solid (yield: 48.8%).

Statistics shows that 1-Methylpyrazole is playing an increasingly important role. we look forward to future research findings about 930-36-9.

Reference:
Patent; CSPC Weisheng Pharmaceutical Technology (Shijiahuang) Co., Ltd.; Shi, Ying; Gao, Qingzhi; Mi, Yi; Wang, Xuliang; (129 pag.)CN105384739; (2016); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 1120-82-7, The chemical industry reduces the impact on the environment during synthesis 1120-82-7, name is (1H-Pyrazol-1-yl)methanol, I believe this compound will play a more active role in future production and life.

To a Schlenk tube was added Cul (9.5 mg), Pd(Ph3P)2Cl2 (35 mg), compound A (1085) (188 mg, 0.5 mmol), TMS acetylene (98 mg, 1.0 mmol), DMF (2 mL), and Et3N (0.5 mL). The reaction mixture was heated at 80 C for 12 hours. The reaction mixture was cooled and treated with EtOAc and brine. The organic layer was separated, dried, and evaporated. The residue was chromatographed on silica gel to give the TMS intermediate. The TMS intermediate was treated with TBAF (0.6 mmol) in 2 mL dry THF for 15 min. The residue was chromatographed on silica gel to give compound C (115 mg, 17% yield). (1086) [0621] To a solution of (lH-pyrazol-l-yl)methanol (196 mg, 2 mmol) in DCM (2 mL) was added methanesulfonyl chloride (4 mmol). The mixture was stirred at 0 C for 10 minutes then Et3N (6 mmol) was slowly added. After stirring at r.t. for 30 min, all volatiles were removed. 3-(4-Hydroxy-l-oxoisoindolin-2-yl)piperidine-2,6-dione (520 mg, 2 mmol), KHC03 (400 mg, 4 mmol), KI (10 mg) and 4 mL CH3CN were added to the residue. The mixture was heated at reflux overnight. The residue was chromatographed on silica gel to give compound D (210 mg, 31% yield). (1087) [0622] To a solution of compound D (210 mg, 0.62 mmol) in acetic acid (4 mL) was added NIS (321 mg, 0.75 mmol). The reaction was stirred for 1 h prior to being concentrated. The residue was purified by HPLC to afford compound E (156 mg, 54%). ESI-MS: 481.05. (1088) [0623] To a Schlenk tube was added Cul (2 mg), Pd(Ph3P)2Cl2 (4 mg), compound C (1089) (20 mg, 0.06 mmol), compound E (28 mg, 0.06 mmol), DMF (2 mL), and Et3N (0.5 mL). The reaction mixture was heated at 80 C for 12 hours. The reaction mixture was cooled and treated with EtOAc and brine. The organic layer was separated, dried, and evaporated. The residue was subjected to HPLC purification to afford Cpd. No. 82 (25 mg, 64% yield). ESI-MS: 674.05.

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, (1H-Pyrazol-1-yl)methanol, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF MICHIGAN; WANG, Shaomeng; HU, Yang; QIN, Chong; XU, Fuming; HU, Jiantao; ZHOU, Bing; CHEN, Zhou; FERNANDEZ-SALAS, Ester; BAI, Longchuan; McEACHERN, Donna; (198 pag.)WO2018/52945; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 31108-57-3,Some common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, molecular formula is C4H3N3, 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.

Synthesis of III-B17 To a solution of III-B16 (90 mg, 0.2 mmol) and lH-pyrazole-4-carbonitrile (37.9 mg, 0.4 mmol) in acetone (5 mL) was added K2C03 (56.2 mg, 0.4 mmol). After stirring at 25C for 2 h, the reaction mixture was extracted with EtOAc (3 x 30 mL). The combined organic solution was washed with saturated brine (30 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by flash column (0-30% of EtOAc in PE) and then by (1240) Prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*30 5 pm; Condition: water (10 mM NH4HC03)-ACN; Begin B: 70; End B: 90; Gradient Time(min): 7; 100%B Hold (1241) Time(min): 1) to give III-B17 (32.6 mg, 53%) as a solid. 1H NMR (400 MHz, CDCl3) dH 7.86 (s, 1H), 7.81 (s, 1H), 5.04 (dd, J= 18.0, 95.6 Hz, 2H), 3.45-3.33 (m, 5H), 2.50 (t, J= 8.8 Hz, 1H), 2.40-2.23 (m, 2H), 1.88-1.10 (m, 23H), 1.00-0.83 (m, 1H), 0.60 (t, J= 7.6 Hz, 3H); LC-ELSD/MS purity 99%, MS ESI calcd. for C27H38N302 [M-H20+H]+ 436.3, found 436.3

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SAGE THERAPEUTICS, INC.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, G.; BLANCO-PILLADO, Maria, Jesus; LA, Daniel; HARRISON, Boyd, L.; (276 pag.)WO2019/126741; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 288-13-1, name is 1H-Pyrazole, 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 288-13-1, Product Details of 288-13-1

To a solution of 1H-pyrazole (5.00 g) in toluene (67.0 mL) were added dimethylsulfamoyl chloride (7.89 mL) and triethylamine (13.3 mL) at room temperature, and the reaction mixture was stirred at room temperature for 18 hr. The resulting solid was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (6.24 g). 1H NMR (400 MHz, CDCl3) delta 2.91 (6H, s), 6.38 (1H, dd, J = 2.6, 1.8 Hz), 7.72 (1H, d, J = 1.2 Hz), 7.96 (1H, d, J = 2.4 Hz)

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, 1H-Pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Takeda Pharmaceutical Company Limited; NAGAMIYA, Hiroyuki; YOSHIDA, Masato; SETO, Masaki; MARUI, Shogo; ODA, Tsuneo; ISHICHI, Yuji; SUZUKI, Hideo; KUSUMOTO, Tomokazu; YOGO, Takatoshi; RHIM, Chul Yun; YOON, Cheolhwan; LEE, Gil Nam; KANG, Hyun Bin; KIM, Kwang Ok; JEON, Hye Sun; EP2818473; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 694-48-4,Some common heterocyclic compound, 694-48-4, name is 1,3-Dimethyl-1H-pyrazole, molecular formula is C5H8N2, 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.

In a 5 L reactor, equipped with a stirrer, a reflux condenser, an argon inlet, thermometer and dropping funnel, 1,3-dimethyl-1H-pyrazole(500 g, 5.2 mol) was added slowly with stirring to acetic anhydride (1950 mL, 2125 g, 20.8 mol), while maintaining the temperature below 45 C. Concd H2SO4(50 mL, 92 g, 0.94 mol) was added with cooling and stirring and the mixture then was gradually heated to reflux and held at reflux for 6 h. The mixture was then cooled, evaporated at 70 C/7 Torr, and treated with crushed ice (2 kg). By carefully addition of 40% NaOH solution, the pH of the reaction mixture was adjusted to pH 8, then the organic phase was separated and the aqueous phase was extracted with CH2Cl2(2 × 1000 mL).The combined organic phases were washed successively with H2O(500 mL) and brine (500 mL), and dried over MgSO4. The solvent was removed at 7 Torr, and the residue was distilled (110-112 C/10 Torr) to afford the target ketone (452 g, 63%) as thick, light yellow oil, which crystallized upon standing.

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

Reference:
Article; Taydakov, Ilya V.; Krasnoselskiy, Sergey S.; Synthesis; vol. 45; 15; (2013); p. 2188 – 2192;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics