Tag: M.W=0-100

Related Products of 28466-26-4, 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. 28466-26-4 name is 4-Aminopyrazole, 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.

Example 150 3-[(2-chlorophenoxy)methyl]-N-1H-pyrazol-4-ylbenzamide 3-[(2-Chlorophenoxy)methyl]benzoic acid was suspended in tetrahydrofuran (50 mL), and oxalyl chloride (1.03 mL) and N,N-dimethylformamide (catalytic amount) were added. After stirring at room temperature for 30 min, the mixture was added dropwise to a suspension of 1H-pyrazol-4-amine (1.0 g) in N,N-dimethylacetamide (50 mL). After stirring at room temperature for 5 hr, ethyl acetate was added, and the mixture was washed 3 times with saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography and recrystallized from ethyl acetate/hexane to give the object product (280 mg, 7.8%). 1H NMR (300 MHz, DMSO-d6) delta ppm 5.29 (s, 2H) 6.93-7.02 (m, 1H) 7.22-7.35 (m, 2H) 7.46 (dd, J=1.51, 7.91 Hz, 1H) 7.56 (t, J=7.72 Hz, 1H) 7.63-7.70 (m, 1H) 7.85 (brs, 2H) 7.89-7.95 (m, 1H) 8.02-8.06 (m, 1H) 10.47 (s, 1H) 12.63 (brs, 1H)

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

Reference:
Patent; Taniguchi, Takahiko; Miyata, Kenichi; Kubo, Osamu; Matsui, Junji; US2009/325956; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine, molecular formula is C4H7N3, 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. category: pyrazoles-derivatives

Procedure NA mixture of an appropriate amine or aniline, respectively (1.0 mmol), an appropriate carbox- ylic acid (1.0 mmol), HBTU (1.0 mmol), a catalytic amount of 4-dimethylaminopyridine (DMAP), iV-ethyldiisopropylethylamine (1.25 mmol), and dry dichloromethane (2 mL) was stirred at room temperature for 12-48 h. The solvent was evaporated under reduced pressure. The residue was taken up with EtOAc (25 mL) and washed with 5 percent citric acid, water, saturated aqueous NaHCO3 solution, and brine. After drying (MgSO4), the solvent was removed under reduced pressure. The product was purified by preparative TLC, flash chromatography, or preparative HPLC. Purity was confirmed by 1H NMR and LC/ESIMS.For the synthesis of Example 145, gaseous ammonia was introduced into the reaction mixture. No additional amine base was applied.For the synthesis of Example 146, methylammonium chloride was applied as the amine, and the amount of amine base was increased to 2.5 mmol. For the synthesis of Example 147, dimethylammonium chloride was applied as the amine, and the amount of amine base was increased to 2.5 mmol.For the synthesis of Example 148, diethylamine was applied as the solvent. Therefore, no additional amine base was applied. For the preparation of 2-(nonyloxy)acetic acid (Intermediate 5) and 3-(octyloxy)propanoic acid (Intermediate 6), 12-(methylthio)dodecanoic acid (Intermediate 13), 12-(methyl- sulfonyl)dodecanoic acid (Intermediate 14), 10-(methylsulfonamido)decanoic acid (Intermediate 15), 4-aza-3-oxododecanoic acid (Intermediate 16), and l-dodecanoylpyrrolidine-3- carboxylic acid (Intermediate 17) see below.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1192-21-8, its application will become more common.

Reference:
Patent; QUONOVA LLC; WO2009/77844; (2009); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 31230-17-8,Some common heterocyclic compound, 31230-17-8, name is 5-Methyl-1H-pyrazol-3-amine, molecular formula is C4H7N3, 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 1: Synthesis of2-chloro-6-methyl-N-(5-methyl-lH-pyrazol-3-yl)pyrimidin-4-amine. (0234) A suspension of 2,4-dichloro-6-methyl-pyrimidine (120.00 g, 736.2 mmol, 1.00 eq) , 5- methyl-lH-pyrazol-3-amine (78.65 g, 0.81 mol, 1.10 eq) and DIPEA (142.72 g, 1.10 mol, 1.50 eq) in DMSO (400.00 mL) was heated at 60 C for 16 hrs, at which point TLC (PE/EA, 5: 1, 1: 1) analysis showed the reaction was complete. The reaction mixture was cooled to 30 C, poured into ice-water (800 mL), and the resulting mixture was extracted with MTBE (800 mL x 10). The combined organic layers were washed with water (400 mL x 3), brine (400 mL x 3) and dried over Na2S04. After filtration, the filtrate was concentrated under reduced pressure and the residue was recrystallized from DCM (10 mL/g) to afford 2-chloro-6-methyl-N-(5-methyl-lH- pyrazol-3-yl)pyrimidin-4-amine (105.60 g, 472.14 mmol, 64%) as a yellow solid. The structure was confirmed by LC-MS and NMR.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Methyl-1H-pyrazol-3-amine, its application will become more common.

Reference:
Patent; BLUEPRINT MEDICINES CORPORATION; BRUBAKER, Jason, D.; KIM, Joseph, L.; WILSON, Kevin, J.; WILSON, Douglas; DIPIETRO, Lucian, V.; (84 pag.)WO2017/79140; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 31108-57-3,Some common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, molecular formula is C4H3N3, 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 7(2R)-4-(4-cvano-1 H-pyrazol-1 -yl)-N-hvdroxy-2-methyl-2-Step A: (2R)-4-(4-cvano-1 H-pyrazol-1 -yl)-2-methyl-2-(methylsulfonyl)butanoic acid To a solution of 4-cyanopyrazole (0.150 g, 1 .61 mmol, 1 eq) in acetonitrile (10 mL) was added cesium carbonate (1 .31 g, 4.03 mmol, 2.5 eq), sodium iodide (0.048 mg, 0.322 mmol, 0.2 eq) and (R)-ethyl 4-bromo-2-methyl-2- (methylsulfonyl)butanoate (0.555 g, 1 .93 mmol, 1 .2 eq). The mixture was heated at 50 C overnight. The reaction mixture was cooled to room temperature and was filtered via Buchner funnel, and eluted with EtOAc. The filtrate was concentrated under reduced pressure and was diluted with up in tetrahydrofuran (5 mL) and water (5 mL). Lithium hydroxide (0.1 16 g, 4.83 mmol, 3 eq) was added, and the reaction mixture was allowed to stir at room temperature for four hours. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate (10mL), and concentrated again. This yielded (2R)-4-(4-cyano-1 H-pyrazol-1 -yl)-2-methyl-2- (methylsulfonyl)butanoic acid as a yellow oil, which was carried on crude in the next step. LC-MS M+H+ 272.2.

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; BROWN, Matthew F.; CHEN, Jinshan Michael; MELNICK, Michael; MONTGOMERY, Justin I.; REILLY, Usa; WO2012/137099; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 31108-57-3,Some common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, molecular formula is C4H3N3, 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.

In a microwave tube propan-2-yl (2R)-oxirane-2-carboxylate (2.00 g, 15.4 mmol) and 4- cyanopyrazole (3.58 g, 38.4 mmol) were dissolved in isopropanol (10 ml). The RM was heated in a microwave reactor at 100C for 3 h. The RM was concentrated in vacuo, then purified by prep-HPLC: (column: Agela Innoval ODS-2 100mm*350mm; mobile phase: [water (0.1 % TFA) – ACN]; B %: 5 % – 25 %, 20 min) to obtain the title compound as a yellow oil. MS ES+: 224.2. NMR (400MHz, chloroform-) delta 7.94 (s, 1H), 7.78 (s, 1H), 5.13 – 5.06 (m, 1H), 4.51 – 4.48 (m, 2H), 3.72 (s, 1H), 1.32 – 1.26 (m, 6H).

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NODTHERA LIMITED; BOCK, Mark G.; WATT, Alan Paul; PORTER, Roderick Alan; HARRISON, David; (229 pag.)WO2019/25467; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 1072-68-0, name is 1,4-Dimethylpyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C5H8N2

1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole A solution of 1,4-dimethyl-1H-pyrazole (480.0 mg, 4.993 mol) in tetrahydrofuran (20 mL, 300 mmol) at 0 C. was added 1.6 M n-butyllithium in hexane (4.7 mL, 7.5 mmol). The solution was stirred at room temperature for 1 h and then cooled to -78 C. To the solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.63 mL, 7.99 mmol). The reaction mixture was stirred at -78 C. for 0.5 h, then warmed up to 0 C. (taking 0.5 h). The reaction was quenched with brine and extracted with EtOAc (3*). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by combi-flash chromatography and eluted with EtOAc/hexane (0-60%). The purification gave 142 mg of product as white solid.

The synthetic route of 1072-68-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Incyte Corporation; Huang, Taisheng; Feng, Hao; Kong, Lingquan; Wang, Anlai; Ye, Hai Fen; US2013/96144; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 1904-31-0, 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 1904-31-0 as follows.

Example 290a 5-Bromo-1-methyl-3-(1-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one 290a A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (100 mL), 1-methyl-1H-pyrazol-3-amine (970 mg, 10.0 mmol), 3,5-dibromo-1-methylpyridin-2-(1H)-one (2.9 g, 11 mmol), and cesium carbonate (6.5 g, 20.0 mmol). After bubbling nitrogen through the suspension for 10 minutes, tris(dibenzylideneacetone)dipalladium(0) (457 mg, 0.50 mmol) and Xantphos (587 mg, 1.0 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 2 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2 X 50 mL) and the combined organic filtrate was concentrated. The residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 290a as a yellow solid (900 mg, 32%). MS-ESI: [M+H]+ 283.1

According to the analysis of related databases, 1904-31-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F.Hoffmann-La Roche AG; CRAWFORD, James John; ORTWINE, Daniel Fred; WEI, BinQing; YOUNG, Wendy B.; EP2773638; (2015); B1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 1904-31-0, These common heterocyclic compound, 1904-31-0, name is 1-Methyl-1H-pyrazol-3-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.

2-Bromopyridine (1) (1 .Og, 6.3mmol), 1-methyl-I H-pyrazol-3-amine (2) (0.79g,8.2mmol), Xantphos (0.37g, 0.63mmol), and Cs2003 (4.Ig, 12.6mmol) were combined in dry 1,4-dioxane (I5mL). The reaction mixture was then degassed with N2(g), and placed under vacuum for 10mm. Pd2(dba)3 (0.29g, 0.3Immol) was added and the resulting reaction mixture was heated at 90°C for 30h. It wasthen poured onto demineralized water (200mL), and extracted with EtOAc (3 x100mL). The organic phases were combined, dried over Na2SO4, filtered and subsequently evaporated under vacuum. The resulting residue was purified by flash chromatography, eluting with EtOAc/Hexane (1:1) to provide N-(1-methyl- I H-pyrazol-3-yl)pyridin-2-amine (3) as a yellow solid (0.75g, 68percent).LCMS (ES): Found 175.2 [MH].

The synthetic route of 1904-31-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KARUS THERAPEUTICS LTD; SHUTTLEWORTH, Stephen Joseph; TOMASSI, Cyrille Davy; CECIL, Alexander Richard Liam; MACCORMICK, Somhairle; NODES, William John; SILVA, Franck Alexandre; WO2014/72714; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 35277-02-2,Some common heterocyclic compound, 35277-02-2, name is 4-Fluoro-1H-pyrazole, molecular formula is C3H3FN2, 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 solution of 5-chloropyrazine-2-carbonitrile (280 mg, 2.0 mmol) in DMF was added 4-fluoro-1H-pyrazole (170 mg, 2.0 mmol), and potassium acetate (395 mg, 4.0 mmol). The mixture was stirred at the 100C for 4 hours. The reaction mixture was cooled to 20C, poured into brine (25 mL), and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated and purified by column chromatography (hexane: ethyl acetate = 5:1) to give 5-(4-fluoro-1H-pyrazol-1- yl)pyrazine-2-carbonitrile (310 mg, Yield 82%). The structure was confirmed by LC-MS.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Fluoro-1H-pyrazole, its application will become more common.

Reference:
Patent; BLUEPRINT MEDICINES CORPORATION; BRUBAKER, Jason D.; GUZI, Timothy; WILSON, Kevin J.; DIPIETRO, Lucian V.; ZHANG, Yulian; WILSON, Douglas; FLEMING, Paul E.; (137 pag.)WO2018/17983; (2018); A1;,
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