Month: June 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. 288148-34-5, name is 1-Methyl-1H-pyrazole-4-sulfonyl chloride, A new synthetic method of this compound is introduced below., Recommanded Product: 1-Methyl-1H-pyrazole-4-sulfonyl chloride

General procedure: A mixture of the appropriate (aryloxy)ethyl piperidine(0.38 mmol) in CH2Cl2 (3 mL), and TEA (1.14 mmol) was cooled down (ice bath), and arylsulfonyl chloride (0.46 mmol) was added at 0 C in one portion. The reaction mixture was stirred for 2-6 h under cooling. Then, the solvent was evaporated and the sulfonamides were purified using silica gel column with CH2Cl2/MeOH as an eluting system. Free bases were then converted into the hydrochloride salts by treatment of their solution in anhydrous ethanol with 1.25 M HCl in MeOH.; 9.2.6.8 1-Methyl-N-(1-{[2-(t-butyl-2-yl)phenoxy]ethyl}piperidin-4-yl)-N-methyl-1H-pyrazole-sulfonamide (17) Yellow oil, 80 mg following chromatographic purification over silica gel with CH2Cl2/MeOH (9:0.7); LC/MS purity 100%, tR = 4.81, C22H34N4O3S, MW 434.60, Monoisotopic Mass 434.24, [M+H]+ 435.5. 1H NMR (300 MHz, CDCl3) delta 1.37 (s, 9H), 1.50-1.58 (m, 2H), 1.70 (qd, J = 12.17, 3.89 Hz, 2H) 2.19 (td, J = 11.80, 2.23 Hz, 2H), 2.73 (s, 3H), 2.82 (t, J = 6.07 Hz, 2H), 2.97-3.04 (m, 2H), 3.76-3.88 (m, 1H), 3.93 (s, 3H), 4.06 (t, J = 6.06 Hz, 1H), 6.83 (dd, J = 8.21, 1.03 Hz, 1H), 6.87-6.91 (m, 1H), 7.15 (td, J = 7.71, 1.70 Hz, 1H), 7.27 (dd, J = 7.92, 1.44 Hz, 1H), 7.70 (s, 1H), 7.74 (s, 1H). 13C NMR (75 MHz, CDCl3) delta 28.58, 29.28, 29.68, 29.81, 34.81, 39.55, 53.48, 55.09, 57.13, 65.94, 112.03, 120.39, 122.24, 126.64, 126.97, 131.35, 138.10, 138.15, 157.49. Anal. calcd for C22H34N4O3S·2HCl: C: 52.06, H: 7.15, N: 11.04, S: 6.32; Found C: 51.95, H: 6.95, N: 10.82, S: 6.11. Mp for C22H34N4O3S·2HCl: 181.7-182.3 C.

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; Canale, Vittorio; Kurczab, Rafa?; Partyka, Anna; Sata?a, Grzegorz; S?oczy?ska, Karolina; Kos, Tomasz; Jastrz?bska-Wi?sek, Magdalena; Siwek, Agata; P?kala, Elzbieta; Bojarski, Andrzej J.; Weso?owska, Anna; Popik, Piotr; Zajdel, Pawe?; Bioorganic and Medicinal Chemistry; vol. 24; 2; (2016); p. 130 – 139;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 152120-54-2, 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. 152120-54-2, name is tert-Butyl (((tert-butoxycarbonyl)amino)(1H-pyrazol-1-yl)methylene)carbamate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of piperidine-4-carboxylic acid trifluoroacetate salt (0.20 g, 0.82 mmol) in methanol (10 mL), triethylamine (0.20 mL, 1.6 mmol) and N,N’-bis{[(2-methyl-2-propanyl)oxy]carbonyl}-1H-pyrazole-1-carboximidamide (0.30 g, 0.98 mmol) was added and the reaction mixture stirred at room temperature for 18 h. The solvent was evaporated under reduced pressure and the resulting residue dissolved in ethyl acetate and washed with brine. The organic layer was dried and concentrated to dryness to obtain the title compound (200 mg, 76%) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta 3.91 (d, 2H), 3.30 (t, 2H), 2.63-2.66 (m, 1H), 1.90-1.96 (m, 2H), 1.67-1.69 (m, 2H), 1.45 (s, 18H).

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, tert-Butyl (((tert-butoxycarbonyl)amino)(1H-pyrazol-1-yl)methylene)carbamate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ONO PHARMACEUTICAL CO., LTD.; Imagawa, Akira; Kondo, Takashi; Nishiyama, Taihei; Courtney, Steve; Yarnold, Chris; Ichihara, Osamu; Flanagan, Stuart; US2015/152048; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 155377-19-8, name is Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate, 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. Computed Properties of C7H7F3N2O2

(S)-Benzyl 5-(hydroxymethyl)-2,3-dihydro-7/-/-inden-2-ylcarbamate (2.96 mmol, 880mg) was dissolved in DCM (10 ml.) and thionyl chloride (5.92 mmol, 0.432 ml, 704 mg) added. The mixture was stirred at room temperature for 30 min TLC before the solvent was removed under reduced pressure and residual thionylchloride azeotroped with DCM (x3). To the residue was added potassium carbonate (8.88 mmol, 1227 mg) followed by DMF (8 ml) then ethyl 3-(trifluoromethyl)-7/-/-pyrazole-4-carboxylate (2.96 mmol, 616 mg) and the mixture heated to 60 0C. After 1 h the mixture was concentrated and partitioned between EtOAc/H2O and the organic layer was washed with water (x 3). The organic layer was dried, filtered and concentrated to give a yellow oil which was purified by flash chromatography eluting with 15% EtOAc/Heptane to give the desired isomer as a colourless oil (45 mg, 0.092 mmol, 3.1%). 1H NMR (400 MHz, CDCI3) delta 1.34 (t, 3H) 2.75 (m, 2H) 3.25 (m, 2H) 4.33 (q, 2H), 4.50 (m, 1 H) 4.95 (m, 1 H), 5.08 (s, 2H) 5.48 (s, 2H) 7.00 (m, 2H) 7.15 (d, 1 H) 7.34 (m, 5H) 7.99 (s, 1 H).

The synthetic route of Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; N.V. ORGANON; WO2009/147167; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 930-36-9, 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. 930-36-9, name is 1-Methylpyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

The (1 -methyl-1 H-pyrazol-5-yl)acetic acid used in the above procedure was prepared as follows: (i) 1 -Methyl-1 H-pyrazole-5-carbaldehyde was prepared as follows (c.f. Bioorg. Med. Chem., 2001 , 9, 961-982): A solution of 1 -methyl- 1 H-pyrazole (11.0 g, 0.134 mol) in tetrahydrofuran (200 ml) was stirred at -700C under argon. n-Butyl lithium (2.5 M in hexanes, 58.8 ml, 0.147 mol) was added dropwise maintaining the internal reaction temperature below -600C. The mixture was cooled to -700C and N, N- dimethylformamide (40 ml) was added dropwise. The reaction mixture was allowed to warm to room temperature overnight. The mixture was cooled to 00C and water (200 ml) was added followed by ethyl acetate (300 ml). The organic layer was separated and the aqueous layer was re-extracted with ethyl acetate. The combined organic extracts were washed with water, brine, then dried and evaporated. The residue was purified by flash chromatography on silica gel eluting with 0-100% ethyl acetate in hexanes to afford 1 -methyl-1 H-pyrazole-5-carbaldehyde which was used in the next step.

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

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/125600; (2008); A2;,
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 78703-53-4 as follows. Recommanded Product: 1,3-Dimethyl-1H-pyrazole-4-carboxylic acid

1,3-Dimethyl-1H-pyrazole-4-carboxylic acid of formula (III) (7.76 g, 40 mmol)Reflowed with thionyl chloride (47.6 g, 0.4 mol) for 4 hours.When the reaction system turns into a pale yellow transparent liquid,Continue to react for 30 minutes,The reaction stops,After cooling to room temperature, it was distilled under reduced pressure.1,3-dimethyl-1H-pyrazole-4-yl chloride,1,3-Dimethyl-1H-pyrazole-4-yl chloride (2mmol)Add 15ml of dichloromethane,Join(R)-1-phenethyl-1-amine(2.1mmol),Then triethylamine (0.3 g, 3 mmol) was slowly added dropwise at room temperature overnight;TLC (EA: PE=2:1(V)) tracking,After the reaction was completed, it was extracted three times with a dichloromethane/water = 1:1 (V) system.Concentrated organic layer,Extracted with toluene or 75% ethanol,Column chromatography (EA: PE = 2:1 (V)),Obtained (K19)(R)-1,3-dimethyl-N-(1-phenethyl)-1H-pyrazole-4-carboxamide;

According to the analysis of related databases, 78703-53-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Zhejiang University of Technology; Jin Tao; Wang Han; Tan Chengxia; Weng Jianquan; Han Liang; Liu Xinghai; (9 pag.)CN109156471; (2019); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 1192-21-8, These common heterocyclic compound, 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine, 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.

Step 3 Under an atmosphere of nitrogen 1-methyl-1H-pyrazol-5-amine (284.5 mg, 2.93 mmol) was dissolved in THF (17.8 mL) at RT and treated with 1.0M LiHMDS in THF (5.86 mL, 5.86 mmol). The reaction was stirred vigorously for 10 min, and then 90 (280 mg, 1.4647 mmol) was added as a solid in one portion. The 100 mL round bottom reaction flask was equipped with a water cooled condenser and heated to 80° C. The reaction was 30percent complete after 3.5 h, so additional 1.0M LiHMDS was added (8.86 mL, total: 14.72 mL, 14.72 mmol), and the reaction heated at 80° C. for another 2.5 hours (total time at 80° C.=6 h). The reaction mixture was diluted with water (20 mL), transferred to a separatory funnel and washed with DCM (4*30 mL). The DCM washings were combined, and the aqueous layer was neutralized via the addition 1.26 mL of 11.6 M aqueous HCl. The resulting precipitate was collected via vacuum filtration to afford 373 mg (94percent) of 3-(1-methyl-1H-pyrazol-5-ylamino)isoquinoline-6-carboxylic acid (92), which was used without any further purification.

Statistics shows that 1-Methyl-1H-pyrazol-5-amine is playing an increasingly important role. we look forward to future research findings about 1192-21-8.

Reference:
Patent; Genentech, Inc.; Array BioPharma Inc.; Blake, Jim; Chen, Huifen; Chicarelli, Mark; Gaudino, John; Gazzard, Lewis; Kintz, Sam; Mohr, Pete; Robarge, Kirk; Schwarz, Jacob; Zhou, Aihe; US2014/66453; (2014); 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. 1145-01-3, name is 3,5-Diphenyl-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 1145-01-3

General procedure: A mixture of chalcone (1d) (208 mg, 1.0 mmol) and TsNHNH2 (205 mg, 1.1 mmol) in EtOH (2 mL) were stirred at room temperature for 48 h and then EtOH (2 mL), NaOH (44.0 mg, 1.1 mmol) were added and the mixture was heated at reflux for 15 h, then the solvent was removed under reduced pressure, then CH3CN (4 mL), NaOH (60 mg, 1.5 mmol) and benzyl bromide (255 mg, 1.5 mmol) were subsequently added and the mixture was stirred at room temperature for 2 h. The product was extracted with Et2O and the organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. Purification by chromatography on silica gel afforded the desired product 4n as white crystalline solid (276 mg, 89% yield). Mp 114-117 C; deltaH (400 MHz, CDCl3) 5.38 (2H, s), 6.66 (1H, s), 7.09 (2H, d, J 7.2 Hz), 7.21-7.30 (4H, m), 7.32-7.42 (7H, m), 7.87 (2H, d, J 7.2 Hz); deltaC (100 MHz, CDCl3) 53.2, 103.7, 125.6, 126.7, 127.4, 127.6, 128.55, 128.56, 128.6, 128.8, 130.6, 133.4, 137.7, 145.4, 150.9; HRMS (ESI): MH+, found 311.1536. C22H19N2 requires 311.1543, numax (liquid film) 3060, 2955, 2924, 2853, 1452, 1361, 1307 cm-1.

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 1145-01-3.

Reference:
Article; Tang, Meng; Zhang, Fu-Min; Tetrahedron; vol. 69; 5; (2013); p. 1427 – 1433;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 119083-00-0, A common heterocyclic compound, 119083-00-0, name is 1-Methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid, molecular formula is C6H5F3N2O2, 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 159 N-(4-{trans-2-[(cyclopropylmethyl)amino]cyclopropyl}phenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide hydrochloride By a method similar to Example 80, the title compound (56.1 mg) was obtained from tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate (82.8 mg) and 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (63.8 mg). MS (API+): [M+H]+ 379.3. 1H NMR (300 MHz, DMSO-d6) delta 0.29-0.40 (2H, m), 0.52-0.62 (2H, m), 0.95-1.11 (1H, m), 1.18-1.30 (1H, m), 1.39-1.52 (1H, m), 2.32-2.47 (1H, m), 2.82-3.02 (3H, m), 3.98 (3H, s), 7.14 (2H, d, J = 8.6 Hz), 7.61 (2H, d, J = 8.6 Hz), 8.54 (1H, s), 9.01 (2H, brs), 10.12 (1H, s).

The synthetic route of 119083-00-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; TOMITA, Naoki; KAJII, Shigeo; CARY, Douglas Robert; TOMITA, Daisuke; IMAMURA, Shinichi; TSUCHIDA, Ken; MATSUDA, Satoru; HARA, Ryujiro; EP2743256; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 288148-34-5,Some common heterocyclic compound, 288148-34-5, name is 1-Methyl-1H-pyrazole-4-sulfonyl chloride, molecular formula is C4H5ClN2O2S, 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: A mixture of the appropriate (aryloxy)ethyl piperidine(0.38 mmol) in CH2Cl2 (3 mL), and TEA (1.14 mmol) was cooled down (ice bath), and arylsulfonyl chloride (0.46 mmol) was added at 0 C in one portion. The reaction mixture was stirred for 2-6 h under cooling. Then, the solvent was evaporated and the sulfonamides were purified using silica gel column with CH2Cl2/MeOH as an eluting system. Free bases were then converted into the hydrochloride salts by treatment of their solution in anhydrous ethanol with 1.25 M HCl in MeOH.; 9.2.6.4 1-Methyl-N-(1-{2-[(propan-2-yl)phenoxy]ethyl}piperidin-4-yl}-N-methyl-1H-pyrazole-4-sulfonamide (13) Yellow oil, 90 mg following chromatographic purification over silica gel with CH2Cl2/MeOH (9:0.7); LC/MS purity 96%, tR = 4.47, C21H32N4O3S, MW 420.57, Monoisotopic Mass 420.22, [M+H]+ 421.3 1H NMR (300 MHz, CDCl3) delta 1.19 (d, J = 6.92 Hz, 6H), 1.49-1.58 (m, 2H), 1.71 (qd, J = 12.21, 3.88 Hz, 2H), 2.22 (td, J = 11.89, 2.24 Hz, 2H), 2.73 (s, 3H), 2.81 (t, J = 5.72 Hz, 2H), 2.99-3.07 (m, 2H), 3.29 (quin, J = 6.92 Hz, 1H), 3.81 (tt, J = 11.97, 4.22 Hz, 1H), 3.92 (s, 3H), 4.06 (t, J = 5.72 Hz, 2H), 6.80 (dd, J = 8.14, 0.99 Hz, 1H), 6.88-6.94 (m, 1H), 7.12 (td, J = 7.76, 1.73 Hz, 1H), 7.20 (dd, J = 7.53, 1.67 Hz, 1H), 7.70 (d, J = 0.61 Hz, 1H), 7.74 (s, 1H). 13C NMR (75 MHz, CDCl3) delta 22.70, 26.73, 28.60, 29.27, 39.55, 53.47, 55.03, 57.13, 66.40, 111.26, 120.78, 122.21, 126.06, 126.53, 131.37, 137.03, 138.15, 155.79.

The synthetic route of 288148-34-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Canale, Vittorio; Kurczab, Rafa?; Partyka, Anna; Sata?a, Grzegorz; S?oczy?ska, Karolina; Kos, Tomasz; Jastrz?bska-Wi?sek, Magdalena; Siwek, Agata; P?kala, Elzbieta; Bojarski, Andrzej J.; Weso?owska, Anna; Popik, Piotr; Zajdel, Pawe?; Bioorganic and Medicinal Chemistry; vol. 24; 2; (2016); p. 130 – 139;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 313735-62-5, name is 4-Bromo-1-isopropylpyrazole, 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 313735-62-5, COA of Formula: C6H9BrN2

n–Butyllithium (2.5M in hexanes, 1.38 mL, 3.45 mmol) was added over 15 min to a solution of 4-bromo-1-isopropyl-1H-pyrazole (500 mg, 2.65 mmol) in diethyl ether (10 mL) at -78 C. After 30 min, a solution of tri-n-butylstannane chloride (920 muL, 3.45 mmol) in diethyl ether (1 mL) was added and the resultant reaction mixture was left to stir at -78 C for 1 h, then allowed to warm to ambient temperature. The reaction mixture was diluted with diethyl ether (40 mL) and washed with water (20 mL), then brine (20 mL). The organic layer was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford the title product as a colourless oil (98 mg, 94%) which was used without further purification. 1H-NMR (CDCl3, 400MHz): 7.46- 7.42 (m, 1 H); 7.28 (t, J = 4.2Hz, 1 H); 4.59-4.43 (m, 1 H); 1.58-1.42 (m, 12 H); 1.39-1.24 (m, 6 H); 1.02-0.77 (m, 15 H).

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

Reference:
Patent; GENENTECH, INC.; WO2009/151598; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics