Day: July 14, 2021

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

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

Synthetic Route of 1222174-92-6, 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. 1222174-92-6, name is Methyl 5-bromo-1-methyl-1H-pyrazole-3-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A solution of intermediate 2a (506 mg) in dioxane (10 mL) was treated with LiOH solution (2 M, 1 mL) and the mixture was stirred at 70 C. for 1 h. HCl (1 M) was added and the mixture was extracted with EtOAc. The combined organic layers were dried and the volatiles were removed under reduced pressure to yield the desired compound (84% yield). [0358] LC-MS (Method 2): m/z [M+H]+=205.0 (MW calc.=205.01); Rt=0.31 min.

The synthetic route of Methyl 5-bromo-1-methyl-1H-pyrazole-3-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Gruenenthal GmbH; Nordhoff, Sonja; Wachten, Sebastian; Kless, Achim; Voss, Felix; Ritter, Stefanie; US2014/194452; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 1280210-79-8, A common heterocyclic compound, 1280210-79-8, name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, molecular formula is C10H15N3O2, 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 stirred solution of feri-butyl 2,6-dihydropyriOlo[3,4-c]pyrazole-5(4H)- carboxylate (Step A of Intermediate 7) (35 g, 167 mmol) in DMF (500 mL) at 0 C under N2 was added sodium hexamethyldisilazide in THF (351 mL, 351 mmol) and the mixture was stirred at 0 C for 30 min. Isobutylene oxide (74.3 mL, 836 mmol) was then slowly added. The solution was stirred at 0C for 0.5 h and then stirred at room temperature for 1 h. The solution was heated to 80C for 100 min in a microwave oven, cooled to room temperature and evapoarted under vacuum. The residue was purified by column chromatography on silica gel, eluting with a gradient of 0% to 6% CH2Cl2 MeOH (containing 10% NH4OH) to give a mixture of two regioisomers. The mixture of two regioisomers A and B was resolved by chromatography on a ChiralPak AD-H column eluting with 4-40% MeOH/C02 to give isomer A as the faster eluting isomer and isomer B as the slower eluting isomer. NMR (500 MHz, CD3OD) for isomer B: 57.42 (d, 1H); 4.42 (s, 2H); 4.41 (s, 2H); 4.07 (s, 2H); 1.51 (d, 9H); 1.16 (s, 6H). LC-MS: 226.27 (M+l -56).The desired isomer B was treated with 1 : 1 TF A/CH2CI2 for 1 h to give the title compound. NMR (500 MHz, CD3OD): 67.55 (s, 1H); 4.43 (s, 2H); 4.39 (s, 2H); 4.10 (s, 2H); 1.17 (s, 6H). LC-MS: 182.31 (M+l).

The synthetic route of 1280210-79-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; HICKS, Jacqueline, D.; BIFTU, Tesfaye; CHEN, Ping; QIAN, Xiaoxia; WILKENING, Robert, R.; WO2011/146358; (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. 133228-21-4, name is N,N-Dimethyl-1H-pyrazole-1-sulfonamide, A new synthetic method of this compound is introduced below., COA of Formula: C5H9N3O2S

Step A: Preparation of3-Chloro-N,N-dimethyl- 1 H-pyrazole- 1-sulfonamideTo a solution of N-dimethylsulfamoylpyrazole (188.0 g,1.07 mol) in dry tetrahydrofuran (1500 mE) at 78 C. wasadded dropwise a solution of 2.5 M n-butyllithium (472 mE,1.18 mol) in hexane while maintaining the temperature below65 C. Upon completion of the addition the reaction mixturewas maintained at 78 C. for an additional 45 minutes, afterwhich time a solution of hexachloroethane (279 g, 1.18 mol)in tetrahydrofuran (120 mE) was added dropwise. The reac40 tion mixture was maintained for an hour at 78 C., warmedto 20 C. and then quenched with water (1 E). The reactionmixture was extracted with methylene chloride (4×500 mE);the organic extracts were dried over magnesium sulfate andconcentrated. The crude product was further purified by chro45 matography on silica gel using methylene chloride as eluentto afford the title product compound as a yellow oil (160 g).?HNMR(CDC13) oe 3.07 (d, 6H), 6.33 (s, 1H), 7.61 (s, 1H).

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; E I DU PONT DE NEMOURS AND COMPANY; Berger, Richard Alan; Annan, Isaac Billy; Lahm, George Philip; Flexner, John Lindsey; Selby, Thomas Paul; Stevenson, Thomas Martin; US9173400; (2015); B2;,
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. 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Formula: C9H15N3O2

To a solution of 2-(3-bromophenyl)acetic acid (0.5g, 2.32mmol) in DCM (20mL) was added EDCI (0.88g, 0.4.65mmol) at 0 C followed by DIPEA (1.l2mL, 6.97mmol) and finally added tert-butyl 3-amino-5-methyl- 1 H-pyrazole- 1 -carboxylate (0.4g, 2.O9mmol). The reaction mass was stined for 12h at room temperature. The reaction mixture was quenched with ice-water and diluted with DCM. The aqueous layer was separated and extracted with ethyl acetate (2x25mL). The combined organic phase was washed with brine, dried over Na2504, filtered and concentrated under reduced pressure and purified by eluting with 20% ethyl acetate-hexane in combiflash to afford the title compound (0.3g, 60%). LCMS: mlz = 395.9 (M+H).

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 578008-32-9.

Reference:
Patent; AURIGENE DISCOVERY TECHNOLOGIES LIMITED; SAMAJDAR, Susanta; PODDUTOORI, Ramulu; PANDIT, Chetan; MUKHERJEE, Subhendu; GOSWAMI, Rajeev; (126 pag.)WO2016/193939; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

866837-96-9, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, 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. Safety of Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate

11512] A solution of ethyl 5-amino-i-phenyl-1H-pyra-zole-3-carboxylate (CAS: 866837-96-9, 300 mg, 1.3 mmol) in THF (6.5 mE), under nitrogen atmosphere was cooled down to -78 C. Diisobutylaluminum hydride (1 M in toluene, 2.9 mE, 2.9 mmol) was added dropwise to the solution, and the stirring at -78 C. was continued for 1 hour. Methanol was added, and the reaction mixture was stirred for 30 minutes warming to RT. DCM was added, and the organic phase was washed with water. The organic phase was separated using a phase separator and concentrated under reduced pressure. The titled compound was used as such without any further purification.

The synthetic route of 866837-96-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Akkari, Rhalid; Alvey, Luke Jonathan; Bock, Xavier Marie; Claes, Pieter Isabelle Roger; Cowart, Marlon D.; De Lemos, Elsa; Desroy, Nicolas; Duthion, Beranger; Gfesser, Gregory A.; Gosmini, Romain Luc Marie; Housseman, Christopher Gaetan; Jansen, Koen Karel; Ji, Jianguo; Kym, Philip R.; Lefrancois, Jean-Michel; Mammoliti, Oscar; Menet, Christel Jeanne Marie; Newsome, Gregory John Robert; Palisse, Adeline Marie Elise; Patel, Sachin V; Pizzonero, Mathieu Rafael; Shrestha, Anurupa; Swift, Elizabeth C.; Van der Plas, Steven Emiel; Wang, Xueqing; (454 pag.)US2017/101406; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 852443-61-9, name is 3-(Trifluoromethyl)-1H-pyrazol-5-amine, molecular formula is C4H4F3N3, 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. Application In Synthesis of 3-(Trifluoromethyl)-1H-pyrazol-5-amine

Tert-butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-l-carboxylate (1.0 g, ca. 2.77 mmol), 3- (trifluoromethyl)-lH-pyrazol-5 -amine (0.28 g, 1.85 mmol) and potassium phosphate (0.79 g, 3.70 mmol) were suspended in 1 -methoxy-2-propanol (10 ml) in a 20 ml microwave vial. The vial was capped and the mixture was heated in a microwave to 180C for 15 min. After cooling to RT, the solvent was evaporated and the residue was treated with water and ethyl acetate. After separation of the layers the aqueous phase was neutralized by addition of HQ 4N and extracted with ethyl acetate. The collected organic layers were dried over magnesium sulfate, filtered and evaporated. The crude product was purified by preparative HPLC (Method 1A). The combined product fractions were neutralized with a 33% ammonia solution and then acetonitrile was evaporated. The aqueous phase was extracted with ethyl acetate and the collected organic fractions were dried over sodium sulfate, filtered and evaporated under vacuo to yield the title compound (132 mg, 19% of theory). LC-MS (Method IB): Rt = 1.06 min, MS (ESIPos): m/z = 387 [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 852443-61-9, its application will become more common.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ELLERMANN, Manuel; VALOT, Gaelle; CANCHO GRANDE, Yolanda; HAssFELD, Jorma; KINZEL, Tom; KOeBBERLING, Johannes; BEYER, Kristin; ROeHRIG, Susanne; SPERZEL, Michael; STAMPFUss, Jan; MEYER, Imke; KOeLLNBERGER, Maria; BURKHARDT, Nils; SCHLEMMER, Karl-Heinz; STEGMANN, Christian; SCHUHMACHER, Joachim; WERNER, Matthias; HEIERMANN, Joerg; HENGEVELD, Willem Jan; (764 pag.)WO2016/71216; (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. 3469-69-0, name is 4-Iodopyrazole, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 3469-69-0

4-Iodo-l-(4-methoxybenzyl)-lH-pyrazole According to Scheme 9 Step 1 : A suspension of 4-iodo-lH-pyrazole (26.3 mmol, 5.11 g), l-(chloromethyl)-4-methoxybenzene (29.0 mmol, 3.95 mL) and K2CO3 (39.5 mmol, 5.46 g) in acetonitrile (150 mL) was heated at 6O0C overnight. The reaction mixture was cooled to room temperature and was filtered. The filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel using DCM as eluent to afford 4-iodo-l-(4-methoxybenzyl)-lH-pyrazole (23.2 mmol, 7.3 g, 88%) as a yellow solid. UPLC-MS: RT = 1.02 min; MS m/z ES+= 315.

According to the analysis of related databases, 3469-69-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ADDEX PHARMA S.A.; BOLEA, Christelle; WO2010/79239; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 478968-48-8 as follows. HPLC of Formula: C7H10N2O3

Step 4. Ethyl 3-methoxy-l-pyrimidin-2-yl-lH-pyrazole-4-carboxylate; Sodium hydride (60% in mineral oil, 528 mg, 13.2 mmol) is added portion wise to a solution of ethyl 3-methoxy-lH-pyrazole-4-carboxylate (1.5 g, 8.81 mmol) in 40 mL of THF at RT. Evolution of H2 (g) is observed. After about 5-10 min, 2-chloropyrirnidine (1.0 g, 8.81 mmol) is added, and the resulting reaction mixture is stirred at reflux for 15 h. After cooling to RT, the reaction is quenched with 10 mL of sat. NH4Cl and 10 mL of water and extracted with CH2Cl2 (2 x 40 mL). The combined organic extracts are dried (Na2SO4), filtered, and evaporated in vacuo to give a brown solid. Purification by silica gel column chromatography (gradient from 50% EtOAc/hexane to EtOAc) affords the title compound as a fluffy white solid.

According to the analysis of related databases, 478968-48-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NEUROGEN CORPORATION; WO2009/12482; (2009); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics