Day: May 19, 2021

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. 4027-57-0, name is Ethyl 5-methylpyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: Ethyl 5-methylpyrazole-3-carboxylate

Reference 4 Preparation of 3-formyl-5-methylpyrazole; Under nitrogen environment, 3-ethoxycarbonyl-5-methylpyrazole (1.0 g, 4.34 mmol) was dissolved in 15 ml of purified toluene, and DIBAL (8.68 ml, 8.62 mmol) was slowly added and stirred at -78C. The reaction progress and completion were confirmed using TLC (hexane : EtOAc = 6 : 1). Upon completion of the reaction, MeOH and water were slowly added to the reaction mixture and the resulting mixture was filtered through a celite bed, and the aqueous layer was extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The concentrate was separated by column chromatography (hexane : EtOAc : CH2Cl2 = 3 : 1 : 1) to obtain the title compound. Yield: 82.4% 1H NMR (300 MHz, CDCl3) delta 9.92 (s, 1H), 6.68 (s, 1H), 2.82 (s, 3H)

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; Korea Institute of Science and Technology; EP1757590; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 113808-86-9,Some common heterocyclic compound, 113808-86-9, name is 3,5-Dimethylpyrazole-4-carboxylic Acid, molecular formula is C6H8N2O2, 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 3,5-dimethyl-1H-pyrazole-4-carboxylic acid (18 mg, 0.13 mmol), HOBt*H2O (0.13 mmol), N-Methylmorpholine (1 mmol), 4-Dimethylaminopyridine (0.01 mmol) in 0.75 mL of DMF, a solution of intermediate 5 (0.11 mmol in 1 mL DMF) was added followed by EDC (neat, 0.13 mmol). The tube was closed with a screw cap and shaken over night at 40 C. 0.1 ml TFA was added and the volume was adjusted to 2.2 ml with DMF. The solution was filtered and submitted to preparative RP-HPLC purification to give 5-[4-(3,5-Dimethyl-1 H-pyrazole-4-carbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid (2-methoxy-pyridin-4-ylmethyl)-amide trifluoroacetate as a colorless film (33 mg, 52%). 1 H NMR (DMSO-d6, 500 MHz) d ppm 9.22 (t, 1 H), 8.1 (d, 1 H), 7.80 (d, 1 H), 7.30 (bs, 1 H), 6.90 (d, 1 H), 6.69 (s, 1 H), 4.6 (bs, 2H), 4.40 (bs, 2H), 4.3-3.7 (broad signal, 4H), 3.7 (s, 3H), 3.5-3.0 (broad signal, 4H), 2.13 (s, 6H). LC/MS (Method 3); Rt = 1.15 min; detected mass: m/z = 469.31 ([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 3,5-Dimethylpyrazole-4-carboxylic Acid, its application will become more common.

Reference:
Patent; SANOFI; The designation of the inventor has not yet been filed; EP2881390; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 50877-41-3,Some common heterocyclic compound, 50877-41-3, name is 1-Benzyl-4-bromo-1H-pyrazole, molecular formula is C10H9BrN2, 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 2: Preparation of l-benzyl-4-(l-ethoxyvinyl)-lH-pyrazole [00168] Nitrogen was purged into a solution of l-benzyl-4-bromo-lH-pyrazole (0.55 g, 2.32 mmol) and tributyl(l-ethoxyvinyl)stannane (0.862 niL, 2.55 mmol) in toluene (15 niL) for 15 minutes. Then tetrakis(triphenylphosphine)palladium(0) (0.134 g, 0.116 mmol) was added and the reaction mixture was heated at 110 C for 12 h. The reaction mixture was filtered through celite and the filtrate was evaporated to afford the title compound l-benzyl-4-(l-ethoxyvinyl)- lH-pyrazole (0.52 g, crude) as a black liquid. The crude material was as such taken for next step without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Benzyl-4-bromo-1H-pyrazole, its application will become more common.

Reference:
Patent; MNEMOSYNE PHARMACEUTICALS, INC.; ANDERSON, David, R.; VOLKMANN, Robert, A.; MENNITI, Frank, S.; (181 pag.)WO2016/49165; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 96450-53-2, These common heterocyclic compound, 96450-53-2, name is 1-(2-Chloroethyl)-1H-pyrazole, 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.

A solution of Boc methylenedioxybenzenesulfonamide free phenol (0.010 g, 0.020 mmol) in acetone (1 ML) was combined with cesium carbonate (0.015 g, 0.047 mmol), 1-(2-chloroethyl)pyrazole (0.004 9, 0.031 mmol) and sodium iodide (~1 mg, 0.007 mmol).The solution was heated to 55 C. with stirring for 60 hours, and was cooled and dried in vacuo to give a yellow oil.Flash column chromatography (1:3 ethyl acetate/hexane) gave Boc methylenedioxybenzenesulfonamide ethylpyrazole tethered product (0.0015 g, 13%) as a colourless oil: Rf=0.20 (1:1 ethyl acetate/hexane); coupled LCMS showed the product as a single major peak with m/z 631 [M+H]+ at RT of 1.65 min.

The synthetic route of 96450-53-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Vertex Pharmaceuticals Incorporated.; US2004/122000; (2004); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 50-33-9,Some common heterocyclic compound, 50-33-9, name is Phenylbutazone, molecular formula is C19H20N2O2, 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.

3-((2R,3R)-1-(Dimethylamino)-2-methylpentan-3-yl)phenol (250 mg) was dissolved while heating in as little ethanol as possible. 4-Butyl-1 ,2-diphenylpyrazolidine-3,5- dione (Phenylbutazone, 339 mg) was dissolved in H2O/ethanol under heating. The solutions were mixed, heated to reflux for 12 hours and allowed to cool to room temperature overnight. The solvent was removed in vacuo and the residue was dried by freeze drying to obtain a white solid (589 mg).

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

Reference:
Patent; GRUeNENTHAL GMBH; WO2007/128412; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 2820-38-4, A common heterocyclic compound, 2820-38-4, name is 3,5-Dimethyl-1H-pyrazol-4-ol, molecular formula is C5H8N2O, 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.

A mixture of 3,5-dimethyl- lH-pyrazol-4-ol (386 mg, 3.44 mmol), N-( – bromopropyl)phthalimide (1.16 g, 3.78 mmol), Cs2C03 (2.24 g, 6.88 mmol) and acetone (20 mL) was heated at reflux for 16 h. The mixture was filtered and concentrated under reduced pressure to give a thick oil, which was purified by flash chromatography (90% EtOAc/petroleum spirits) gave the title compound (290 mg, 25%). 1H NMR (400 MHz, CDC13) delta 2.07 (2 H, dd, 7 13.6, 6.4 Hz, CH2CH2N), 2.19 (6 H, s, 2 x CH3), 3.86 (4 H, td, 7 6.6, 4.7 Hz, CH2N,CH20), 7.67 (2 H, dd, 7 5.4, 3.1, AR), 7.81 (2 H, dd, 7 5.5, 3.1 HZ, Ar);13C NMR (100 MHz, CDC13) delta 9.85, 29.24, 35.43, 72.04, 123.25, 132.13, 133.99, 134.61, 138.93, 168.39; HRMS (ESI+): m/z 300.1341 [M+H]+ (calcd. [Ci6Hi7N303+H]+ 300.1343).

The synthetic route of 2820-38-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; THE FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH; THE UNIVERSITY OF MELBOURNE; WILLIAMS, Spencer John; JARROTT, Bevyn; (94 pag.)WO2016/149765; (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. 111573-59-2, name is 3-(Dimethoxymethyl)-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 111573-59-2

2.3 kg of formic acid at 0-15 degrees Celsius was slowly added dropwise to 13.8 kg of Compound 3 in 15 L of water.Subsequently, the reaction mixture was magnetically stirred at 25 C for 12 hours,After the reaction was light yellow solid precipitation,Filter the 10 L water and wash the filter cake to obtain 643 g yellow solid compound 4.

According to the analysis of related databases, 111573-59-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Wuhan Yao Ming Kant, Immanuel New Drug Development Co., Ltd.; Xu Xueqin; Zhou Qiang; An Ziqiang; Liu Yueling; He Yanping; Jiao Jiasheng; Wang Ruiqi; Wu Yan; Xu Fujun; Yu Lingbo; Ma Rujian; (6 pag.)CN107235982; (2017); A;,
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. 191980-54-8, name is 4-Iodo-1-trityl-1H-pyrazole, A new synthetic method of this compound is introduced below., COA of Formula: C22H17IN2

Example 95: Methyl (S)-{2,3,9-trimethyl-4-[4-(1H-pyrazol-4-yl)phenyl]-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl}acetate To a mixture of the compound described in Starting Material Synthetic Example 1 (420 mg), tetrakistriphenylphosphine palladium”(58 mg) and 4-iodo-1-trityl-1H-pyrazole (654 mg) were added tetrahydrofuran (1.5 mL) and 2 M aqueous sodium carbonate solution (1.5 mL), and the mixture was stirred at 100C for 4 hr. After cooling, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol=100:1) to give compound (729 mg). The obtained compound (729 mg) was dissolved in methanol (3 mL). Trifluoroacetic acid (154 muL) was added, and the mixture was stirred at room temperature for 2 days. After completion of the reaction, the mixture was neutralized with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol=100:1) to give the title compound (162 mg) . 1H-NMR (400 MHz, DMSO-d6) delta: 2.67 (3H, s), 2.43 (3H, s), 2.62 (3H, s), 3.39-3.52 (2H, m), 3.68 (3H, s), 4.49 (1H, t, J = 7.2 Hz), 7.39 (2H, d, J = 8.2 Hz), 7.65 (2H, d, J = 8.2 Hz), 8.11 (2H, brs) MS (ESI) m/z: 447 (M+H)+.

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; Mitsubishi Tanabe Pharma Corporation; EP1887008; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 920006-32-2, 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. 920006-32-2 name is 1-Isopropylpyrazole-5-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.

To a solution of HATU (0.253 g) in DMF (3 ml) was added 1 -(1 -methylethyl)-1 H-pyrazole- 5-carboxylic acid (0.102 g) and DIPEA (0.21 1 ml) and the mixure was left to stand for 10 min. 6-(1 H-lndol-4-yl)-1 H-indazol-4-amine (0.075 g) dissolved in DMF (3 ml) was added and the solution was left to stand at RT for 18 h. DMF was removed by blow down (not to dryness) and the residue was dissolved in chloroform (1 ml) and loaded onto an aminopropyl SPE (2 g) (pre-conditioned with methanol (6 ml) and chloroform (6 ml)). The mixure was left on the column for 2 h then eluted with ethyl acetate:methanol (1 :1 , 10 ml). The solvent was blown down to dryness and the residue was dissolved in DMSO:methanol (1 ml, 1 :1 ) and purified by MDAP (method A). The solvent was removed in vacuo and dried in an vacuum oven (50 C) overnight to give title compound, 18 mg. LCMS (method A) Rt = 3.23 min, MH+ = 385.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Isopropylpyrazole-5-carboxylic Acid, and friends who are interested can also refer to it.

Reference:
Patent; GLAXO GROUP LIMITED; BALDWIN, Ian, Robert; DOWN, Kenneth, David; FAULDER, Paul; GAINES, Simon; HAMBLIN, Julie, Nicole; LE, Joelle; LUNNISS, Christopher, James; PARR, Nigel, James; RITCHIE, Timothy, John; ROBINSON, John, Edward; SIMPSON, Juliet, Kay; SMETHURST, Christian, Alan, Paul; WO2011/67364; (2011); 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. 39205-87-3, name is 3-Nitro-1H-pyrazole-4-carbonitrile, A new synthetic method of this compound is introduced below., Formula: C4H2N4O2

EXAMPLE 7 3-(1-Ethyl-3-nitro-4-pyrazolyl)-acrylic acid 20 g. 3-nitro-4-pyrazole-carbonitrile are stirred with 17.5 ml. ethyl iodide, 21 g. potassium carbonate and 145 ml. 1,2-dimethoxyethane for 2 hours under reflux, followed by cooling. The inorganic material is then filtered off with suction. The filtrate is evaporated in a vacuum, the evaporation residue is dissolved in about 250 ml. ethyl acetate and this solution is shaken up with 150 ml. aqueous 2N potassium carbonate solution and with sodium thiosulphate solution. The organic phase is separated off, dried and evaporated in a vacuum to give 21.7 g. crude 1-ethyl-3-nitro-4-pyrazole carbonitrile in the form of an oil. 15.7 g.

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 Mannheim GmbH; US4105772; (1978); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics