Tag: M.W:100-200

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. 948570-75-0, name is 1-(2-Methoxyethyl)-4-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., HPLC of Formula: C6H9N3O3

1-(2-methoxyethyl)-4-nitro-1H-pyrazole (84 mg, 0.49 mmol) and -chloro-6-(2,6-dichloro-3,5-dimethoxy phenyl)pyrido[3,4-d]pyrimidine (200 mg, 0.54 mmol) were dissolved into DMA (15 mL), then CuI (112 mg, 0.59 mmol), PivOH (15 mg, 0.15 mmol), K2CO3 (88 mg, 0.64 mmol) and Pd(PPh3)2Cl2 (34 mg, 0.05 mmol) were added, the mixture was heated to 140 C. under N2 and stirred for 1 h. The reaction was completed, and the mixture was concentrated to remove the sol vent by reduced pressure and separated by fast silica gel column (PE/EA 2:1) to obtain compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(1-(2-methoxyethyl)-4-nitro-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidine (103 mg, yield 42%). MS m/z (ESI): 505 [M+1]+.

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; Abbisko Therapeutics Co., Ltd.; YANG, Fei; DENG, Haibing; YING, Haiyan; YU, Hongping; CHEN, Zhui; XU, Yaochang; (604 pag.)US2019/270742; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 17635-45-9, name is 4-Pyrazol-1-yl-phenylamine, 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 17635-45-9, Recommanded Product: 4-Pyrazol-1-yl-phenylamine

General procedure: A dry 50 mL capacity carousel reaction tube was charged with the relevant substituted indole (1.5 mmol), and this starting material dissolved in dry THF (12 mL). Oxalyl chloride (144 muL, 209 mg, 1.65 mmol) was added and the mixture stirred at room temp. After 24 h, either N,N-diisopropylethylamine (590 muL, 438 mg, 3.4 mmol) or 2,6-lutidine(396 muL, 364 mg, 3.4 mmol) was introduced to the reaction, followed by the relevant amine (1.8 mmol). The temperature was raised to 45 °C, and heating continued for 18 h. The solvent was evaporated, then the residue resuspended in a mixture of ethyl acetate (20 mL) and brine (10 mL) and stirred vigorously for 30 min. After passing through a liquid-liquid extraction column, ensuring washing through of the column with additional ethyl acetate, a second extraction was carried out with sat. NH4Cl (10 mL) in the same manner. Product solutions were then evaporated to dryness giving the crude indole-3-glyoxylamide derivatives, which were purified as necessary (see Supplementary Information for individual compound details). Typically, two sequential recrystallizations, from ethyl acetate-hexane followed by 2-propanol-water, afforded final products of good purity. For products derived from poorly nucleophilic anilines (p-1H-pyrazol-1-ylaniline,p-pyrrol-1-ylaniline and p-morpholinoaniline), a further modification was used. Immediately following introduction of the arylamine to the reaction mixture, DMAP (18 mg, 0.15 mmol, 10 molpercent) was added to assist the final step, as its use was found to enhance the extent of conversion in the final step in such cases.

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, 4-Pyrazol-1-yl-phenylamine, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Thompson, Mark J.; Louth, Jennifer C.; Ferrara, Steven; Jackson, Matthew P.; Sorrell, Fiona J.; Cochrane, Edward J.; Gever, Joel; Baxendale, Sarah; Silber, B. Michael; Roehl, Henry H.; Chen, Beining; European Journal of Medicinal Chemistry; vol. 46; 9; (2011); p. 4125 – 4132;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 72760-85-1, name is 3-Amino-5-(methylthio)-1H-pyrazole-4-carbonitrile, 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 72760-85-1, name: 3-Amino-5-(methylthio)-1H-pyrazole-4-carbonitrile

General procedure: An equimolar mixture of Int-I (chalcones) and Int-II (5-amino-3-(methylthio)-1H-pyrazole-4-carbonitrile) was refluxed in n-butanol for 4-5 h. The completion of reaction was confirmed by Thin Layer Chromatography using (6:4- hexane: ethyl acetate) as a mobile phase. The reaction mixture was then allowed to cool and the resulting solid was filtered and washed with diethyl ether to remove impurities. The procedure was repeated 3-4 times to free the product from impurities.

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:
Article; Baluja, Shipra; Nandha, Kajal; Journal of Molecular Liquids; vol. 201; (2015); p. 90 – 95;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 89717-64-6, name is 4-Bromo-3-nitro-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 89717-64-6, Formula: C3H2BrN3O2

To a solution of 4-bromo-3- nitro-lH-pyrazole (1.3 g, 6.8 mmol) in DMF (15 mL) was added benzyl bromide (1.72 g, 10.1 mmol) and K2CO3 (1.86 g, 13.5 mmol) at room temperature. The reaction mixture was stirred at 80 C for 12 h. After cooling down to room temperature, the mixture was diluted with water (40 mL) and extracted with EtOAc (40 mL x 2). The combined organic layers were washed with water (30 mL) and brine (30 mL), dried over Na2S04, filtered and concentrated. The residue was purified by silica gel chromatography (eluted with petroleum ether/EtOAc from 0% to 20%) to give the l-benzyl-4-bromo-3-nitro-lH-pyrazole (1.5 g, Yield: 78%) as a yellow solid. ESI-LCMS (m/z): 282.0 [M+1]; 1HNMR (400 MHz, CD3OD): delta 8.05 (s, 1H), 7.43-7.32 (m, 5H), 5.41 (s, 2H) ppm

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

Reference:
Patent; EPIZYME, INC.; CAMPBELL, John Emmerson; (178 pag.)WO2016/44666; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

82560-12-1, name is 3-Amino-5-tert-butylpyrazole, 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. Quality Control of 3-Amino-5-tert-butylpyrazole

To a solution of 5-amino-3-tert-butylpyrazole (3.93 g, 28.2 mmol) in CH2Cl2 (140 mL) was added di-tert-butyl dicarbonate (6.22 g, 28.5 mmol) in one portion. The resulting solution was stirred at room temp. for 13 h, then diluted with EtOAc (500 mL). The organic layer was washed with water (2 x 300 mL), dried (MgSO4) and concentrated under reduced pressure. The solid residue was triturated (100 mL hexane) to give the desired carbamate (6.26 g, 92%): mp 63-64 C; TLC Rf (5% acetone/95% CH2Cl2); 1H-NMR (DMSO-d6) delta 1.15 (s, 9H), 1.54 (s, 9H), 5.22 (s, 1H), 6.11 (s, 2H); FAB-MS m/z ((M+H)+).

The synthetic route of 82560-12-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Bayer Pharmaceuticals Corp.; EP1047418; (2005); B1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 35691-93-1, name is Ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate, molecular formula is C8H12N2O2, 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 Ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate

A microwave vial was charged with ethyl 3,5-dimethyl-1 H-pyrazole-4-carboxylate (1.00 g, 5.95 mmol), methyl vinyl sulfone (0.521 ml, 5.95 mmol), K2CO3 (2.465 g, 17.84 mmol) and DMF (15 ml), and the mixture was irradiated for 30 minutes at 135 C in a personal microwave reactor. The reaction mixture was diluted with EtOAc, washed with brine and dried over magnesium sulfate. The solvent was removed to give ethyl 3,5-dimethyl-1-[2-(methylsulfonyl)ethyl]-1 H-pyrazole-4-carboxylate (1.61 g, 99 % yield). 1 H NMR (400 MHz, CHLOROFORM-d) delta ppm 4.47 (t, J=6.2 Hz, 2 H), 4.30 (q, J=IA Hz, 2 H), 3.65 (t, J=6.2 Hz, 2 H), 2.61 (s, 3 H), 2.60 (s, 3 H), 2.42 (s, 3 H), 1.37 (t, J=IA Hz, 3 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 35691-93-1, its application will become more common.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2008/157273; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 15754-60-6, name is 1-(tert-Butyl)-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. HPLC of Formula: C7H12N2

Flash vacuum pyrolysis reactions were carried out by distillation of the substrate in vacuo through an electrically heated silica furnace tube (35 × 2.5 cm). Products were trapped in a U-tube situated at the exit point of the furnace and cooled with liquid N2. Conditions were first established on a small scale (20 mg) where the product(s) were dissolved in a deuterated solvent and analyzed directly by 1H NMR spectroscopy. Larger-scale pyrolyses, involving 0.1 g or more of substrate, were usually removed from the trap by solution in CH2Cl2 (30mL). The precursors and pyrolysis conditions [quantity of precursor, inlet temperature (Ti), furnace temperature (Tf), pressure range (P), and pyrolysis time (t)] and yields are stated. This compound was too volatile for normal inlet conditions. It was therefore cooled in an acetone-dry ice bath, which was slowly removed to allow sublimation (20 mg, Ti acetone/dry ice bath, Tf 600-850 C, P 0.03 Torr, t 15 min).

The synthetic route of 1-(tert-Butyl)-1H-pyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Article; Mackay, Martha; Nortcliffe, Andrew; McNab, Hamish; Hulme, Alison N.; Synthesis; vol. 47; 2; (2015); p. 242 – 248;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 5334-40-7, 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. 5334-40-7, name is 4-Nitro-1H-pyrazole-3-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows.

Step 1: Into a 100 mL round bottom flask containing a solution of methyl 4-nitro-1H-pyrazole- 3-carboxylate (5.0 g, 29 mmol) in dimethylformamide (50 mL) were added anhydrous potassium carbonate (8.0 g, 58 mmol) and 2-iodopropane (5.8 mL, 58 mmol) at 0 oC and the mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified flash chromatography eluting with ethyl acetate in petroleum ether (10-20percent) to afford a mixture of regioisomers, methyl 1-isopropyl-4-nitro-1H-pyrazole-5-carboxylate (2.2 g, 35percent yield) as a colorless oil and methyl 1-isopropyl-4-nitro-1H-pyrazole-3-carboxylate as an oil. For methyl 1- isopropyl-4-nitro-1H-pyrazole-5-carboxylate; 1H NMR (CD3OD, 400 MHz): delta 8.16 (s, 1H), 4.75-4.71 (m, 1H), 4.04 (s, 3H), 1.52 (d, J = 6.6 Hz, 6H). For methyl 1-isopropyl-4-nitro-1H- pyrazole-3-carboxylate; 1H NMR (CD3OD, 400 MHz): delta 8.68 (s, 1H), 4.66-4.59 (m, 1H), 3.95 (s, 3H), 1.55 (d, J = 6.7 Hz, 6H).

The chemical industry reduces the impact on the environment during synthesis 4-Nitro-1H-pyrazole-3-carboxylic acid. I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIM, Jongwon; ALTMAN, Michael, D.; BRUBAKER, Jason, D.; GIBEAU, Craig, R.; (94 pag.)WO2016/144847; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 55864-87-4, 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. 55864-87-4 name is Ethyl 4-nitro-1H-pyrazole-3-carboxylate, 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.

A mixture of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (6.40 g, 34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 h. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-lH-pyrazole-3- carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1H NMR (400 MHz, DMSOd6) delta 12.7 (s, IH)5 7.1 (s, IH), 4.8 (s, 2H)5 4.3 (q, 2H), 1.3 (t, 3H)).

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

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2006/70198; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 5744-80-9, A common heterocyclic compound, 5744-80-9, name is 3-Bromo-1,5-dimethyl-1H-pyrazole, molecular formula is C5H7BrN2, 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.

Example 173 3-amino-5-(dicyclopropylmethyl)-7-(1,5-dimethyl-1H-pyrazol-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (0879) A mixture of 3-amino-7-bromo-5-(dicyclopropylmethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (300 mg) obtained in Example 78, Step C, 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (283 mg), tetrakis(triphenylphosphine)palladium(0) (107 mg), potassium acetate (182 mg) and N,N-dimethylacetamide (4 mL) was stirred under an argon atmosphere at 110C for 4 hr. The reaction mixture was cooled to room temperature, 3-bromo-1,5-dimethyl-1H-pyrazole (195 mg), aqueous sodium carbonate solution (2 M, 0.928 mL) and tetrakis(triphenylphosphine)palladium(0) (107 mg) were added. Under an argon atmosphere, the reaction mixture was stirred at 130C for 5 hr. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane/ethyl acetate) and further purified by silica gel chromatography (diol silica gel, hexane/ethyl acetate). The obtained solid was crystallized from ethyl acetate/diisopropyl ether to give the title compound (104 mg).

The synthetic route of 5744-80-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; YOSHIDA, Masato; NAGAMIYA, Hiroyuki; OHBA, Yusuke; SETO, Masaki; YOGO, Takatoshi; SASAKI, Satoshi; TOKUNAGA, Norihito; ASO, Kazuyoshi; (298 pag.)EP2980089; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics