Day: September 16, 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. 127107-23-7, name is 1-Methyl-1H-pyrazol-4-amine hydrochloride, A new synthetic method of this compound is introduced below., Computed Properties of C4H8ClN3

The 2,5-dichloro-N-(6-methoxyhexahydrofuro[3,2-b]furan-3-yl)pyrimidin-4-amine (430mg, 1.4046 mmol), diisopropylethylamine (546.7 mg, 4.23 mmol) and 1-methylpyrazol-4-amine hydrochloride (283.3 mg,2.12 mmol) was dissolved in n-BuOH (10 mL), the temperature of the reaction solution was raised to 150 C, sealed tube reaction for 23 hours, and then concentrated under reduced pressure.The residue was purified by silica gel column chromatography (DCM / MeOH (v / v) = 50/1) to afford the title compound as a white solid which was recrystallized from acetone to give the title compound as a white solid (220 mg, 42.6% ).

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; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Li Minxiong; Li Xiaobo; Dai Weilong; Wang Tingjin; (74 pag.)CN104926824; (2017); B;,
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. 7119-95-1, name is 1-Nitropyrazole, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

A solution of 1-nitro-1H-pyrazole (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into 160 mL of hexanes. A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent). H1-NMR (400 MHz, DMSO-d6) delta: 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz).

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; Berthel, Steven Joseph; Kester, Robert Francis; Murphy, Douglas Eric; Prins, Thomas Jay; Ruebsam, Frank; Sarabu, Ramakanth; Tran, Chinh Viet; Vourloumis, Dionisios; US2008/21032; (2008); 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. 139756-02-8, name is 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide, A new synthetic method of this compound is introduced below., name: 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide

General procedure: A mixture of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 1a (1.0 mmol), Ketones 2(1.0 mmol) and InCl3 (10 mol%,) in acetonitrile (6 mL) was stirred at room temperature for the time indicated in Table 3. After completion of the reaction (indicated by TLC) the reaction mixture was filtered and wash with acetonitrile (2 X 5 mL) to remove the insoluble catalyst. The filtrate was collected and concentrated under vacuum. The solid isolated was triturated with MTBE (10 mL), filtered and dried to give the desired product.

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:
Article; Ismail; Kuthati, Bhaskar; Thalari, Gangadhar; Bommarapu, Venkatesham; Mulakayala, Chaitanya; Chitta, Suresh Kumar; Mulakayala, Naveen; Bioorganic and Medicinal Chemistry Letters; vol. 27; 6; (2017); p. 1446 – 1450;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 13808-65-6, 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. 13808-65-6 name is 4-Bromo-3-phenyl-1H-pyrazole, 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.

[0164] In a microwave tube was placed ethyl 2-bromothiazole-4-carboxylate (1058 mg, 4.48 mmol), 3-bromo-4-phenyl-1H-pyrrole (995 mg, 4.48 mmol), and K2C03 (929 mg, 6.72 mmol). The tube was sealed and DMSO (4 ml) was added. The mixture was heated at 120C for 4 h. The mixture was poured into vigorously stirred H20 (100 mL), and the solid was filtered, triturated with H20, and dried. The solid was re-dissolved in EtOAc and filtered. Some undissolved material was the hydrolized acid. The filtrate was concentrated and triturated with ca. 3% EtOAc/hexane to give ethyl 2-(4-bromo-3-phenyl- 1H-pyrazol- 1- yl)thiazole-4-carboxylate (1329 mg, 3.51 mmol, 78% yield).

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

Reference:
Patent; THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES; VANDERBILT UNIVERSITY; MALONEY, David J.; JADHAV, Ajit; BANTUKALLU, Ganesha Rai; BRIMACOMBE, Kyle Ryan; MOTT, Bryan T.; YANG, Shyh Ming; URBAN, Daniel Jason; HU, Xin; SIMEONOV, Anton; KOUZNETSOVA, Jennifer L.; WATERSON, Alex Gregory; SULIKOWSKI, Gary Allen; KIM, Kwangho; CHRISTOV, Plamen; JANA, Somnath; (387 pag.)WO2016/109559; (2016); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 25016-12-0,Some common heterocyclic compound, 25016-12-0, name is 1,3-Dimethyl-1H-pyrazole-4-carbaldehyde, molecular formula is C6H8N2O, 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.

General procedure: To a solution of Example 13 (53 mg, 0.17 mmol, 1.0 eq) and 1-methyl-1H-imidazole-2-carbaldehyde (28 mg, 0.25 mmol, 1.5 eq) in THF (2 mL) under a N2 atmosphere was added NaBH(OAc)3 (72 mg, 0.34 mmol, 2.0 eq) and the mixture was stirred at RT overnight. The mixture was purified by C18 reverse phase column (Biotage, 30% to 70% ACN in water, 0.1% TFA) to afford the title compound (22 mg, 34%) as a white solid. LCMS: [M+H]+ 384.2. 1H NMR (400 MHz, CDCl3) delta 8.10 (d, J=8.4 Hz, 1H), 7.65 (d, J=7.2 Hz, 1H), 7.41 (s, 2H), 7.20 (s, 1H), 4.78 (s, 2H), 3.98 (s, 3H), 3.80 (s, 2H), 3.40 (m, 2H), 3.17-3.00 (m, 3H), 2.59 (s, 3H), 2.24 (m, 2H), 1.95 (m, 2H).

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-4-carbaldehyde, its application will become more common.

Reference:
Patent; Ribon Therapeutics Inc.; Schenkel, Laurie B.; Vasbinder, Melissa Marie; Kuntz, Kevin Wayne; Swinger, Kerren Kalai; (179 pag.)US2019/194174; (2019); 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. 49633-25-2, name is 3-Isopropylpyrazole, A new synthetic method of this compound is introduced below., Recommanded Product: 3-Isopropylpyrazole

Part A – 4-Bromo-3-isopropylpyrazole To a stirred solution of sodium acetate (19.7 g., 0.24 mole) in acetic acid (100 ml.) and water (15 ml.), 3-isopropylpyrazole (11.0 g., 0.1 mole) was added, followed by dropwise addition of bromine (16.0 g., 0.11 mole) keeping the internal temperature below 15 C. The mixture was kept at 25 C. for 15 hours, treated with water (200 ml.) and extracted with ethyl ether (3 * 50 ml.), and the ether layer washed with water (1 * 50 ml.) dried, (sodium sulfate) and evaporated under reduced pressure. The resultant pale yellow oil was distilled to give 4-bromo-3-isopropylpyrazole (15.3 g., 81%) with a boiling point of 85 C. at 0.06 mm Hg. Analysis: Calc’d. for C6 H9 BrN2: C, 38.11; H, 4.80; N, 14.82; Br, 42.27. Found: C, 37.91; H, 4.89; N, 14.83; Br, 42.15.

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; The Upjohn Company; US3957480; (1976); A;,
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. 17635-44-8, name is 3,4,5-Tribromopyrazole, This compound has unique chemical properties. The synthetic route is as follows., Formula: C3HBr3N2

To a solution of 3,4,5-tribromo-1H-pyrazole (25 g, 81.96 mmol, 1.0 eq) in THF (300 ml), was added n-BuLi (2.5 M in hexanes, 65.6 ml, 164 mmol, 2.0 eq) over 30 min at -78 C. and the RM was stirred at this temperature for 30 min. The RM was quenched by the dropwise addition of MeOH-THF (2:3; 125 ml) at -78 C., and stirred for an additional 1.5 h while gradually allowing it to warm to RT. The solvent was removed under reduced pressure. The residue was diluted with diethyl ether (600 ml), washed with aq. HCl (0.5 N, 60 ml) and brine (75 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to afford the title product (16 g, 86%)

According to the analysis of related databases, 17635-44-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GRUeNENTHAL GMBH; Schunk, Stefan; Reich, Melanie; Koenigs, Rene Michael; (62 pag.)US2017/101397; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 3469-69-0, name is 4-Iodopyrazole, 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 3469-69-0, Application In Synthesis of 4-Iodopyrazole

General procedure: To a solution of pyrazole 1-13 (1 equiv.) and trifluoroacetic acid (0.01 equiv.) in dichloromethane(for 1 mol of pyrazole – 1 L of dichloromethane were used) ethyl vinyl ether (1.27 equiv.) wasadded dropwise, keeping the temperature between 28-32 C (exothermic reaction) and left to stir atroom temperature for 12-78 hours. Dichloromethane was washed with saturated NaHCO3 solution(1 × 250 mL – for 1 L of dichloromethane) then with deionized H2O (1 × 250 mL). Organic layerwas dried with anhydrous Na2SO4, and evaporated under reduced pressure. Products were purifiedby distillation or recrystallization.

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

Reference:
Article; Mazeikaite, Rita; Sudzius, Jurgis; Urbelis, Gintaras; Labanauskas, Linas; ARKIVOC; vol. 2014; 6; (2014); p. 54 – 71;,
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. 1621-91-6, name is 1H-Pyrazole-3-carboxylic acid, A new synthetic method of this compound is introduced below., name: 1H-Pyrazole-3-carboxylic acid

Ethyl 1H-pyrazole-3-carboxylate (6) A 100 mL Schlenk tube was dried under vacuum, filled with nitrogen and charged with 0.5 g (4.461 mmol, 1.0 eq) 1H-pyrazol-3-carboxylic acid which was dissolved in 20 mL EtOH. After adding 1.31 g (0.72 mL, 13.382 mmol, 3.0 eq) conc. H2SO4 the colorless reaction mixture was heated to reflux (100° C.) and stirred at this temperature for 4 h. TLC analysis (DCM/MeOH 95:5) indicated full conversion of the starting material. After cooling to rt the mixture was transferred to a flask to remove the solvent at a rotary evaporator. The colorless residue was diluted in 20 mL water and neutralized with 17 mL saturated aqueous NaHCO3 solution. Thereby a white solid precipitated. The aqueous layer was extracted with EtOAc (4*50 mL), dried over MgSO4 and the solvent was evaporated under reduced pressure to yield the pure title compound. yield: 582.5 mg (93percent); colorless solid; M.p.: 158-161° C.; Rf (DCM/MeOH 95:5): 0.42; 1H-NMR (300 MHz, CDCl3): delta (ppm)=10.69 (bs, 1H, NH), 7.84 (d, 4J=2.1 Hz, 1H, Ar-H), 6.86 (d, 4J=2.1 Hz, 1H, Ar-H), 4.43 (q, 3J=7.2 Hz, 2H, CH2), 1.41 (t, 3J=7.2 Hz, 3H, CH3); 13C-NMR (75.5 MHz, CDCl3): delta (ppm)=161.8 (C=O), 141.6 (Cq), 132.3 (CHAr), 107.8 (CHAr), 61.1 (CH2), 14.3 (CH3); GC-MS (NM-50_S2): tR=4.655 min (m/z=140.1, 98.0percent M+, BP: 95.0).

The synthetic route of 1621-91-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Technische Universitaet Graz; Karl-Franzens-Universitaet Graz; Schweiger, Martina; Romauch, Matthias; Zimmermann, Robert; Mayer, Nicole; Breinbauer, Rolf; US9206115; (2015); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 175277-11-9,Some common heterocyclic compound, 175277-11-9, name is 3-tert-Butyl-1-methylpyrazole-5-carboxylic Acid, molecular formula is C9H14N2O2, 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.

46) 3-(tert-butyl)-N-(6-fluoro-2,3-dimethoxybenzyl)-1-methyl-1H-pyrazole-5-carboxamide To a solution of aldehyde (250 mg, 1.36 mmol, 1.0 eq) in toluene (15 mL) was added 2,4-dimethoxybenzyl amine (227 mg, 1.36 mmol, 1.0 eq) and the reaction mixture was stirred at room temperature for 24 h. Toluene was removed to give a residue, which was taken in MeOH (15 mL) and then NaBH4 (103 mg, 2.72 mmol, 2.0 eq) was added slowly. The reaction mixture was stirred at room temperature for 6 h. Solvent was removed and the residue was extracted in Ethyl acetate and stirred with saturated aq NaHCO3 for 1 h. The organic layer was collected, dried and solvent was removed to give the crude amine, which was used in the next step without further purification. To a solution of the crude amine (0.45 mmol, 1.1 eq) in DMF (5 mL) were added the acid (75 mg, 0.407 mmol, 1.0 eq), DIEA (262 mg, 2.04 mmol, 5 eq) and HBTU (205 mg, 0.54 mmol, 1.2 eq) and the reaction mixture was stirred at rt for 12 h. The reaction mixture was then diluted with ethyl acetate (20 mL) and washed with 10% aq HCl (1*20 mL), sat NaHCO3 (1*20 mL) and water (4*20 mL). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was purified by column chromatography (EtOAc/Hexane 25% to 75%)) to give the amide, which was directly used in the next step. The amide was treated with 95% TFA:H2O for 12 h. TFA was removed and azeotroped with toluene to give a residue, which was purified by column chromatography (EtOAc/Hexane 10% to 50%) to give the desired product. Mass Spectrum (LCMS, ESI Pos.) Calcd. For C18H25FN3O3: 350.0 (M+H), Found 350.0.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-tert-Butyl-1-methylpyrazole-5-carboxylic Acid, its application will become more common.

Reference:
Patent; Prosetta Antiviral ,Inc.; Selvarajah, Suganya; Paulvannan, Kumar; (58 pag.)US2018/118679; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics