Category: pyrazoles-derivatives

Some common heterocyclic compound, 398495-65-3, name is 5-tert-Butyl 1-ethyl 3-aminopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate, molecular formula is C13H20N4O4, 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. SDS of cas: 398495-65-3

Step 2. 5-(tert-butyl) 1-ethyl 3-((6-bromo-2-fluoro-3-methoxybenzyl)amino)-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylateSodium triacetoxyborohydride (286.09 mg; 0.136 mmol; 2.00 eq.) was added to a solution of 5-(tert-butyl) 1-ethyl 3-amino-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylate (200.00 mg; 0.06 mmol; 1.00 eq.) and 6-bromo-2-fluoro-3-methoxybenzaldehyde (157.28 mg; 0.06 mmol; 1.00 eq.) in dichloromethane (4.00 ml), followed by the addition of acetic acid (40.53 mg; 0.06 mmol; 1.00 eq.) and the reaction mix was left stirring at RT. After 1 h no traces of product were seen by LCMS. Some molecular sieves were added to the reaction flask and after 1 h a peak corresponding to the desired product was observed. Reaction mix was left stirring overnight. The reaction was quenched by addition of NaHCO3 solution and extracted twice with DCM. The combined organics were dried over Na2SO4 filtered and concentrated. The crude was purified on silica gel column using 0-100% EtOAc on hexanes to give the desired 5-(tert-butyl) 1-ethyl 3-((6-bromo-2-fluoro-3-methoxybenzyl)amino)-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylate (70 mg). MS (M+H)+ found for C21H26BrFN4O5: 513/515.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 398495-65-3, its application will become more common.

Reference:
Patent; Global Blood Therapeutics, Inc.; Li, Zhe; Xu, Qing; Yu, Chul; Yee, Calvin; Gwaltney,, II, Stephen L.; Metcalf, Brian W.; Richards, Steven; Lardy, Matthew A.; Setti, Lina; Sham, Hing; US2015/315198; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 5334-39-4, name is 3-Methyl-4-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 5334-39-4, COA of Formula: C4H5N3O2

To a solution of cw-3-benzyloxycyclobutanol (17 g, 95 ,4 mmol) and 3-methyl-4-nitro-lH-pyrazole (12.1 g, 95.4 mmol) in THF (350 mL) was added PPh3 (37.5 g, 143 mmol). Then, DIAD (28.9 g, 143 mmol) was added slowly at 0 C, and the mixture was stirred at 15 C for 20 h. The mixture was quenched with H2Q (100 mL), then filtered. The filtrate was then extracted with EtOAc (3 x 70 mL), The organic phase was washed with brine (30 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel colum chromatography (PE:EtOAc = 10: 1 to 7: 1), to give trans- l-(3-benzyloxycyclobutyl)-5-methyl-4-nitro-pyrazole and trans-l-(3- benzyloxycyclobutyl)-3-methyl-4-nitro-pyrazoleTo a solution of /ra>v-l-(3-benzyloxycyclobutyl)-5-methyl-4-nitro-pyrazole and rra?is-l-(3-benzyloxyxyck)butyl)-3-methyl-4-nitro-pyrazole (19.5 g, 67.9 mmol) in DCM (200 mL) was added BC1 (1 M, 26.5 mL) at 0 C, and the mixture was stirred at 0 C for 2 h. The mixture was poured into water (200 mL) slowly, then extracted with DCM (2 x 100 mL). The organic phase was washed with aqueous ai K ()·. (50 mL), brine (40 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography (PE/EtOAc = 2 : 1 to 1 : 1), to give trans-3-[5- methyi-4-nitro-pyrazol- 1 -yl]cyclobutanol and trans-3-[3-methyl-4-nitro-pyrazol-1-yl]cyclobutanol as a mixture as a white soli d . To a mixture of trans-3~[5-methyl-4-nitro- pyrazol- 1 -yl] cyclobutanol and rrav-3-[3-methyl-4-nitro-pyrazol-l-yl]cyclobutanol ( 1.4 g, 7.1 mmol) in CL CN (100 mL) was added Cul (541 mg, 2.84 mmol) and 2,2-difluoro-2-fluorosulfonyl-acetic acid ( 1.9 g, 10.65 mmol) at 15 C, and the mixture was stirred at 55 C for 2 h. The mixture was quenched with water (5 mL), The solvent was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE: EtOAc = 10: 1), to give trans- 1 – [3 -(difluoromethoxy)cyciobutyl] -5 -methy 1-4-nitr o-pyrazole and trans- 1-[3- (difluoroinethoxy)cyclobutyi]~3-methyl-4-nitro~pyrazole as a yellow solid To a mixture of ras-l-[3- (difiuoi methoxy)cyclobutyl |-5~methyl-4″nitro-pyrazoie and ro;/s~l~[3-(difluoromethoxy)cyclobutyl]-3- methyl-4-nitro-pyrazole (350 mg, 1.42 mmol) and NH4CI (379 mg, 7.08 mmol) in EtOH (8,8 mL) and H20 (2.2 mL) was added powder Fe (395 mg, 7.08 mmol) at 15 C, then the mixture was stirred at 80 C for 2 h. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The mixture was extracted with EtOAc (2 x 30 mL). The organic phase was washed with brine (10 mL), dried over anhydrous Na2S04, filtered and concentrated to give trans-l-[3- (dif]uoromethoxy)cyclobutyl]-5-methyl-pyrazol-4-amine and rranA”-l-[3-(di£luoromethox’)cyclobutyl]-3- methyl-pyrazol-4-amme as a brown oil. LCMS: RT 2.06 min, m/z ==393.1 |M+H]+. To a mixture of trans- 1 – f 3 -(difluoromethoxy )cyclobutyl] -5 -methyl -pyrazol -4-amine and trans- 1 – f 3 – (difluoromethoxy)cyclobutyl]-3-methyl-pyrazol-4-amine (270 mg, 1.24 mmol) in 1,4-dioxane (10 mL) was added 2~chloro-N-methy3-5~(trifliJoromethyi)pyrimidin-4-amine (262 mg, 1.24 mmol) and TsOH-H20 (236 mg, 1.24 mmol) at 15 C. The mixture was warmed to 90 C and stirred for 2 h. The reaction was quenched with H20 ( 1 mL), then concentrated under reduced pressure. The crude was purified by prep-HPLC (FA) to give trans-N2-[l-[3-(difluoromethoxy)cyclobutyl]-5-methyl-pyrazol-4-yl]-N4-methyl-5- (trifluoromethyl)pyrimidine-2,4-diamine (D-25): 1H NMR (400 MHz, CDC13): delta rhorhoiotaeta 8.08 (s, 1 H) 7.71 – 7.98 (br. s., 1 H), 6.23 (t, J =3.2 Hz, 1 H), 5 ,20 (t, .7 =3,2 Hz, 1 H), 4.1 (t, J =3.2 Hz, 1 H), 4 ,75 (br. s., 1 H), 3,03 (s, 3 H), 2.97 – 3.03 (m, 2 H), 2.68 – 2,73 (m, 2 H), 2,20 (s, 3 H); HPLC: RT 2.06 mm; MS: m/z: 393.1 [M+H]+ trans-N2-[l-[3-(difluoromethoxy)cyclobutyl]-3-methyl-pyrazol-4-yl]-]N4-methyl-5- (trifluoromethyl)pyrimidine-2,4-diamine (D-26): ‘H NMR (400 MHz, CDCi3): delta rhorhoetaiota 8.21 (s, 1 H), 8.07 (br, s,, 1 ). 7.89 (s, 1 H), 6,22 (t, J =3 ,2 Hz, I H), 5.34 (br. s., 1 H), 4.96-5.02 (m, 1 H), 4,81 – 4.90 (m, 1 H) 3.04 – 3.15 (m, 3 H), 2.84 – 2.96 (m, 2 H), 2.65 – 2.78 (m, 2 H), 2.31 (s, 3 H); HPLC: RT 2.06 min; MS: m/z: 393.1 j M 1 1 ] –

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; DENALI THERAPEUTICS INC.; ESTRADA, Anthony A.; FENG, Jianwen A.; LYSSIKATOS, Joseph P.; SWEENEY, Zachary K.; DE VICENTE FIDALGO, Javier; (271 pag.)WO2017/87905; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

89181-79-3, name is 3-Amino-1-methyl-1H-pyrazole-4-carboxamide, 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. Application In Synthesis of 3-Amino-1-methyl-1H-pyrazole-4-carboxamide

General procedure: To a solution of carboxamides 11-14 (0.015 mol) in dry acetone(10 mL), benzoyl isothiocyante (0.0165 mol, 1.1 equiv) was addedand refluxed at 60 C for 12 h. The reaction mixture was cooled.The resulting yellow solid was filtered, washed with acetone and dried under vacuum. The crude product was further recrystalizedfrom methanol to obtain a pure solids.

The synthetic route of 89181-79-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Venkatesan, Gopalakrishnan; Paira, Priyankar; Cheong, Siew Lee; Vamsikrishna, Kosaraju; Federico, Stephanie; Klotz, Karl-Norbert; Spalluto, Giampiero; Pastorin, Giorgia; Bioorganic and Medicinal Chemistry; vol. 22; 5; (2014); p. 1751 – 1765;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 29097-00-5, 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. 29097-00-5, name is Methyl 3-amino-1H-pyrazole-4-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

a) A mixture of 11.5 g of methyl 5-aminopyrazole-4-carboxylate, 16 ml of ethyl omega, omega, omega-trifluoroacetoacetate and 150 g of polyphosphoric acid was heated to 100 while stirring for 16 hours. After cooling to 20, cold water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with 1N aqueous hydrochloric acid and aqueous saturated sodium chloride solution and then dried over Na2 SO4. The solvent was evaporated in a vacuum and the residue was taken up in ether. The solid product was filtered off under suction and recrystallized from 2-propanol. There was obtained an isomer of the product, namely methyl 7-hydroxy-5-(trifluoromethyl)pyrazolo-[1,5-a]pyrimidine-3-carboxylate of m.p. 216-217. The product enriched in the mother liquors was crystallized from ethyl acetate. There was obtained methyl 5-hydroxy-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate of m.p. 149-150.

The synthetic route of Methyl 3-amino-1H-pyrazole-4-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoffmann-La Roche Inc.; US5036064; (1991); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 930-36-9, 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. 930-36-9 name is 1-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.

Step 1) Method A: Phosphorus oxychloride (6.92 g, 45.1 mmol, 1.5 eq.) was cooled to 0C and then added drop- wise to anhydrous DMF (3.50 mL, 45.2 mmol, 1.5 eq.) at 0C. The colorless DMF solution soon becomes orange. The mixture was stirred for 1 hour at room temperature and then heated to 80C. 1 -Methyl- IH-pyrazole (2.5 mL, 30.2 mmol) is then added drop-wise to the reaction, and the resulting mixture was stirred 3 hours at 95C. The reaction was then quenched by slow addition to ice (40 g) via Pasteur pipette. The pH of the resulting solution was 2, and it was raised to 5 by slowly adding 12N aqueous sodium hydroxide solution (11.2 mL total). The resulting aqueous solution was extracted with dichloromethane (3 x 40 mL). At this point, the pH of the aqueous layer had dropped to 3, therefore additional 12 N NaOH solution (1 mL) was added to bring the pH to 6. The aqueous layer was then extracted further with ether (4 x 40 mL). The combined extracts were then dried over sodium sulfate, filtered and concentrated (at about 40-50C). After drying for 30 minutes under vacuum, a brown oil was recovered (3.79 g) which NMR indicated consisted of a mixture of product, starting material and DMF (52 wt %, 22 wt %, and 26 wt %, respectively). The calculated yield of was 59% and the calculated yield for recovery of unreacted starting material, was 34%. This crude material may be used without further purification in the next step.

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; SHUMWAY, Stuart Denham; TONIATTI, Carlo; ROBERTS, Brian Scott; MARTIN, Melissa M.; WO2013/39854; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 3994-50-1, A common heterocyclic compound, 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, molecular formula is C4H5N3O2, 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 500 mL round bottom flask containing 4-nitro-i-H-pyrazole (5g, 44.2 mmol) was added sodium hydroxide (1M, 200 mL) and dimethyl sulfate (31 mL, 330 mmol). The mixture was stirred at room temperature for 72 h and the mixture was extracted with CH2C12 (2 x 150 mL). The organic layer was separated and the solvent was distilled off to yield 1- methyl-4-nitro- lH-pyrazole as a white solid (4.30 g, 76%). Following WO 2007/99326, to a 500 mL 3-neck-round bottom flask was added 1- methyl-4-nitro- lH-pyrazole (4.30 g, 33.8 mmol) and THF (12 mL). The mixture was cooled to -78 C and lithium hexamethyldisilazide in THF (1M, 88.4 mL, 90 mmol) was added dropwise via an addition funnel over 20 min. The brown mixture was stirred for 30 min and warmed to -45 C over 30 min. The mixture was cooled back down to -78 C and hexachloroethane (10.5 g, 44.2 mmol) dissolved in THF (20 mL) was added via an addition funnel over 15 min. The mixture was stirred for 2.5 h, warmed from -78 C to -40 C and the reaction was monitored by LCMS. Upon completion of the reaction, the reaction was quenched with a solution of saturated NH4C1 (150 mL), and ethyl acetate (100 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layer was washed with water (150 mL), dried over Na2S04 and the organic solvent was distilled off. The crude product was purified via flash chromatography (CH2C12/ 7% MeOH) to yield 5-chloro-l-methyl-4-nitro- lH-pyrazole as a white solid (1.40 g, 20%). 1H NMR (400 MHz, CDC13) delta 8.13 (s, 1H), 3.92 (s, 3H); ESIMS m/z = 162.0 (M+l)

The synthetic route of 3994-50-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BURCH, Jason; CHEN, Huifen; WANG, Xiaojing; WO2015/140189; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 5334-39-4, 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. 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 550 mg (2.45 mmol) 4-[(5-methyl-4-nitro-1 H-pyrazol-1 – yl)methyl]piperidine and 4-[(3-methyl-4-nitro-1 H-pyrazol-1 -yl)methyl]piperidine (intermediate 18B) in 5 mL DMF was stirred with 195 muL (2.06 mmol) ethanesulfonyl chloride and 1.23 mL (8.83 mmol) triethylamine overnight. Saturated aqueous sodium bicarbonate was added to the reaction. The mixture was extracted with ethyl acetate, and the combined organic phase was washed with brine, dried, filtered, and evaporated. 628 mg of the desired title compounds as crude product were obtained which were used without further purification. 1 H NMR (400 MHz, DMSO d6): delta (ppm) = 1.19 (t, 3H), 1.20 / 1.27 (m, 2H), 1.57 (m, 2H), 2.00 (m, 1 H), 2.42 / 2.62 (s, 3H), 2.76 (m, 2H), 3.01 (q, 2H), 3.58 (m, 2H), 4.03 / 4.09 (d, 2H), 8.80 / 8.24 (s, 1 H).

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

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BUCHMANN, Bernd; HEISLER, Iring; MUeLLER, Thomas; CLEVE, Arwed; HEROULT, Melanie; NEUHAUS, Roland; PETRUL, Heike; QUANZ-SCHOeFFEL, Maria; (194 pag.)WO2016/12474; (2016); 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. 83-10-3, name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 83-10-3

Step 2) N-(5-hydroxypyridin-2-yl)-2,5-dimethyl-3-oxo-1-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide A suspension of 2-amino-5-hydroxypyridine hydrochloride (500 mg, 3.41 mmol) and Et3N (0.77 mL, 5.5 mmol) in DMF (8 mL) was stirred at rt for 1 hour. At the same time, to a solution of 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (0.64 g, 2.75 mmol), HOAT (449 mg, 3.3 mmol) and EDCI (0.63 g, 3.3 mmol) in DMF (8 mL) was added Et3N (0.77 mL, 5.5 mmol) drop wise. The mixture was stirred at rt for 1 hour, followed by the addition of the above prepared mixture. The reaction was heated at 60 C. for 5 hours, then cooled to rt and diluted with water (150 mL). and adjust to pH=6 with HCl (1 M). The mixture was extracted with EtOAc (20 mL*4), and the combined organic phases were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=10/1) to give the title compound as a pale yellow solid (699 mg, 78%). MS (ESI, pos. ion) m/z: 325.1 [M+H]+.

The synthetic route of 83-10-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; Calitor Sciences, LLC; Xi, Ning; Wu, Yanjun; Liao, Min; Feng, Yanming; US2015/37280; (2015); 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., Recommanded Product: 37687-24-4

A solution of 849 mg (4.00 mmol) diethyl pyrazole-3,5-dicarboxylate and 1.02 g (4.00 mmol) 2-bromo-1-(4-tert-butyl-phenyl)-ethanone in 4 ml acetone is treated with 663 mg (4.80 mmol) potassium carbonate. The resulting suspension is stirred overnight at room temperature. The reaction mixture is partitioned between water and dichloromethane. The organic phase is dried over sodium sulfate and evaporated to give 1-[2-(4-tert-butyl-phenyl)-2-oxo-ethyl]-1H-pyrazole-3,5-dicarboxylic acid diethyl ester as light yellow foam; HPLC/MS 2.77 (A), [M+H] 387.

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; MERCK PATENT GMBH; DORSCH, Dieter; BUCHSTALLER, Hans-Peter; MOINET, Gerard; WEGENER, Ansgar; WO2013/143663; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 35344-95-7, The chemical industry reduces the impact on the environment during synthesis 35344-95-7, name is 1H-Pyrazole-4-carbaldehyde, I believe this compound will play a more active role in future production and life.

To a stirred solution of tert-butyl 6-methylsulfonyloxy-2-azaspiro[3.3]heptane-2- carboxylate 23-2 (500 mg, 1.72 mmol) and lH-pyrazole-4-carbaldehyde 23-3 (164.89 mg, 1.72 mmol) inDMF (10 mL) was added cesium carbonate (1.12 g, 3.43 mmol) and the reaction mixture was stirred at 80C for 16 hours. The reaction mixture was diluted with cold water and EtOAc, and the layers were separated. The organic layer was washed with water, brine, dried over NaiiSCfi and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford tert-butyl 6-(3-formylpyrazol-l-yl)-2-azaspiro[3.3]heptane-2- carboxylate 23-4 (420 mg, 1.44 mmol, 84.01% yield) as gummy solid. LC MS: ES+ 292.2.

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-4-carbaldehyde, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; C4 THERAPEUTICS, INC.; VEITS, Gesine, Kerstin; HE, Minsheng; HENDERSON, James, A.; NASVESCHUK, Christopher, G.; PHILLIPS, Andrew, J.; GOOD, Andrew, Charles; (471 pag.)WO2019/191112; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics