Category: pyrazoles-derivatives

Electric Literature of 20154-03-4, 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. 20154-03-4, name is 3-(Trifluoromethyl)-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows.

Compound Bl (3 g; 8.43 mmol), 3-trifluoromethylpyrazole (3.44 g; 25.28 mmol), potassium carbonate (7 g; 50.58 mmol) and copper iodide (322 mg; 1.69 mmol) were suspended in 50 mL of nitrobenzene in a stream of nitrogen, and the temperature of the water bath was raised to 200°C under stirring. The mixture was stirred for 2 hours under heating, and then cooled to room temperature. Insolubles were removed by sellaite filtration, and the solvent of the filtrate was distilled off under reduced pressure. Purification of the residue through a silica gel column (hexane:ethyl acetate = 9:1) yielded 2.57 g (yield: 65.4percent) of compound Cl as a colorless liquid. Phosphorescence lambdamax = 452 nm (dichloromethane solution).

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

Reference:
Patent; FUJI PHOTO FILM CO., LTD.; WO2006/98505; (2006); 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. 39806-90-1, name is 4-Iodo-1-methyl-1H-pyrazole, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

A solution of 4-iodo-1-methyl-1H-pyrazole (0.80 g, 3.9 mmol) in THF (7.04 g, 8.00 ml, 98 mmol) was cooled at 0 C. A solution of isopropylmagnesium chloride lithium chloride complex in THF (5.42 ml, 4.23 mmol, 0.78 molar) was added dropwise and the reaction was stifled for 1 hour. A solution of N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (0.733 g, 4.23 mmol) in THF (2 mL) was added dropwise. Cooling was removed after 15 min and reaction was then stirred for 2 hours. To the mixture was added 2 M HCl (20 mL) and it was extracted with AcOEt (3×25 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography to yield (1-methyl-1H-pyrazol-4-yl)(tetrahydro-2H-pyran-4-yl)methanone (220 mg, 1.13 mmol, 29.4% yield). [0365] 1H NMR (600 MHz, CDCl3) delta 7.87 (s, 1H), 7.87 (s, 1H), 4.03 (ddd, J=11.4, 4.1, 2.4 Hz, 2H), 3.92 (s, 3H), 3.49 (td, J=11.7, 2.3 Hz, 211), 3.06 (tt, J=11.3, 3.8 Hz, 1H), 1.86 (dtd, J=13.8, 11.7, 4.4 Hz, 2H), 1.72 (ddd, J=13.4, 3.7, 2.0 Hz, 2H)

The synthetic route of 39806-90-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; H. Lundbeck A/S; Kilburn, John Paul; Rasmussen, Lars Kyhn; Jessing, Mikkel; Eldemenky, Eman Mohammed; Chen, Bin; Jiang, Yu; Hopper, Allen T.; US2014/107340; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 25016-11-9, 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. 25016-11-9 name is 1-Methyl-1H-pyrazole-4-carbaldehyde, 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.

Acetic acid (101muL; 1.76mmol) was added under nitrogen atmosphere, at rt to a solution of intermediate 27 (430mg; 0.88mmol) and 1-methyl-1H-pyrazole-4- carbaldehyde( CAS [25016-11-9]) (194mg; 1.76mmol) in THF (15mL). The mixture was stirred at rt for 3 hours. Subsequently, NaBH(OAc)3 (561mg; 2.65mmol) was added portionwise and the mixture was stirred at rt for 15 hours. The mixture was poured into a mixture of water, and a 10% solution of K2CO3. EtOAc was added and stirred at rt for 15 min and extracted with EtOAc (x2). The organic layers were combined, dried over MgSO4, filtered and evaporated to dryness. The residue was purified by chromatography over silica gel (Stationary phase: irregular SiOH 15-40mum 24g GRACE, Mobile phase: Gradient from 0.1% NH4OH, 97% DCM, 3% MeOH to 0.1% NH4OH, 95% DCM, 5% MeOH). The fractions containing product were collected and evaporated to dryness yielding 420 mg (82%) of intermediate 28.

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

Reference:
Patent; JANSSEN PHARMACEUTICA NV; ANGIBAUD, Patrick, Rene; PANDE, Vineet; HERKERT, Barbara; KROSKY, Daniel, Jason; QUEROLLE, Olivier, Alexis, Georges; PATRICK, Aaron, Nathaniel; PILATTE, Isabelle, Noelle, Constance; (157 pag.)WO2018/109088; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 37687-24-4,Some common heterocyclic compound, 37687-24-4, name is Diethyl 3,5-pyrazoledicarboxylate, molecular formula is C9H12N2O4, 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 250 mL of acetonitrile was dissolved 2-chloro-l-(l -methyl- 1H- pyrazol-4-yl)ethanone (18.3 g, 115 mmol) and diethyl lH-pyrazole-3,5-dicarboxylate (24.5 g, 115 mmol) before finely ground K2CO3 (31.9 g, 231 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was filtered, and the cake was washed with acetonitrile (100 mL). The filtrate was concentrated in vacuo to a thick oil. The oil was dissolved in EtOAc (80 mL), and heptane (200 mL) was added slowly with stirring. The resultant solids were stirred for 2 h, then filtered and washed with heptane. The solids were dried in a vacuum oven to afford the title compound (26.4 g, 67% yield).

The synthetic route of 37687-24-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ANDREWS, Steven W.; BLAKE, James F.; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MORENO, David A.; REN, Li; WALLS, Shane M.; (421 pag.)WO2018/136661; (2018); 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. 17635-45-9, name is 4-Pyrazol-1-yl-phenylamine, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

Example 274 Synthesis of 5-(4-(1H-pyrazol-1-yl)phenylamino)-7-(cyclopropylamino)-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde To 4-(1H-pyrazol-1-yl)aniline (54 mg, 0.34 mmol), Cs2CO3 (130 mg, 0.4 mmol) were added to tert-butyl 5-chloro-3-formyl-2-methylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (100 mg, 0.29 mmol) dissolved in 1,4-dioxane (1.1 mL). Racemic BINAP (11 mg, 0.017 mmol) and palladium(II) acetate (8 mg, 0.011 mmol) were then added. The mixture was sealed and irradiated at 110° C. for 60 min in the microwave. Et2O (3 mL) was added and the solution was filtered. The filtrate was concentrated in vacuo. The crude residue was dissolved in dichloromethane (1.5 mL) and trifluoroacetic acid (1.5 mL). After stirring at room temperature for 1 hour, the solution was concentrated under a stream of air. The crude material was purified by silica gel chromatography (15percent acetone/dichloromethane) to yield the product, 5-(4-(1H-pyrazol-1-yl)phenylamino)-7-(cyclopropylamino)-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde (24 mg, 23percent yield). LCMS (M+1=374)

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; SENHWA BIOSCIENCES, INC.; Haddach, Mustapha; Tran, Joe A.; Pierre, Fabrice; Regan, Collin F.; Raffaele, Nicholas; Ravula, Suchitra; Ryckman, David M.; (417 pag.)US9303033; (2016); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 82560-12-1, The chemical industry reduces the impact on the environment during synthesis 82560-12-1, name is 3-Amino-5-tert-butylpyrazole, I believe this compound will play a more active role in future production and life.

Step j04: 3-Tert-butyl-1H-pyrazol-5-amine (J-lll) (1 equivalents, 40 g) was dissolved in diluted HCl (120 mL of HCl in 120 mL of water) and mixed dropwise with NaNO2 (1 .03 equivalents, 25 g in 100 mL) at 0 – 5 C over a period of 30 min. After stirring for 30 minutes, the reaction mixture was neutralised with Na2CO3. A diazonium salt obtained by reaction of KCN (2.4 equivalents, 48 g), water (120 mL) and CuCN (1 .12 equivalents, 31 g) was added dropwise to the reaction mixture within 30 min and the mixture was stirred for a further 30 min at 75 C. After complete reaction, the reaction mixture was extracted with ethyl acetate (3 x 500 mL), the combined organic phases were dried over sodium sulphate and the solvent was removed under vacuum. The purification (silica gel: 100-200 mesh, eluent: 20 % ethyl acetate/n-hexane) of the residue by column chromatography produced a white solid (J-IV) (6.5 g, 15 %).

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, 3-Amino-5-tert-butylpyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GRUeNENTHAL GMBH; FRANK, Robert; CHRISTOPH, Thomas; DAMANN, Nils; LESCH, Bernhard; BAHRENBERG, Gregor; SAUNDERS, Derek John; STOCKHAUSEN, Hannelore; KIM, Yong-Soo; KIM, Myeong-Seop; LEE, Jeewoo; WO2013/68462; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 31230-17-8, A common heterocyclic compound, 31230-17-8, name is 5-Methyl-1H-pyrazol-3-amine, molecular formula is C4H7N3, 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 solution of compound 12 (84 mg, 0.30 mmol) in DMF (3 mL) at room temperature were added DIPEA (0.103 mL, 0.6 mmol) and 5-methyl-1H-pyrazol-3-amine (88 mg, 0.9 mmol).The reaction mixture was heated at 40° C. overnight.Water was added, and the yellow precipitate was collected by filtration and washed with water.The solid was purified by silica gel chromatography eluting with DCM/MeOH to give compound I (30 mg, 29percent).1H NMR (300 MHz, DMSO-d6) delta 2.19 (s, 3H), 6.54 (s, 1H), 7.40 (m, 2H), 7.68 (t, 1H), 7.9-7.7 (m, 2H), 8.08 (m, 2H), 8.74 (d, 1H), 10.66 (s, 1H), 12.20 (s, 1H); LC-MS (ESI) m/z: 348 (M+H)+.

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; AMBIT BIOSCIENCES CORP.; US2012/53193; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 1904-31-0, name is 1-Methyl-1H-pyrazol-3-amine, 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 1904-31-0, Formula: C4H7N3

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (93 mg, 0.27 mmol), 1-methyl-1H-pyrazol-3-ylamine (29 muL, 0.30 mmol) and N,N-diisopropylethylamine (141 muL, 0.81 mmol) were combined in acetonitrile (1.25 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N’N’-tetramethyluronium hexafluorophosphate (103 mg, 0.27 mmol) was added and the ice bath was removed. After stirring 2 h, the reaction mixture was evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2*3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 mum; 60percent ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-N-(1-methyl-1H-pyrazol-3-yl)-acetamide (79 mg, 69percent) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C18H21ClN4O4S [M+] 424.10, found 425 [M+H+]; H1-NMR (400 MHz, CDCl3) delta ppm 1.64 (m, 4 H, 2*CH2), 1.86 (m, 4 H, 2*CH2), 3.29 (s, 3 H, SO2CH3), 3.85 (s, 3 H, NCH3), 4.88 (p, J=4.1 Hz, 1 H, OCH), 6.69 (d, J=2.3 Hz, 1 H, Ar), 7.28 (d, J=2.3 Hz, 1 H, Ar), 7.55 (dd, Jo=8.2, Jm=1.3 Hz, 1 H, Ar), 7.66 (d, Jm=1.3 Hz, 1 H, Ar), 8.18 (d, Jo=8.2 Hz, 1 H, Ar), 9.16 (s, 1 H, NH).

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-Methyl-1H-pyrazol-3-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Berthel, Steven Joseph; Kester, Robert Francis; Murphy, Douglas Eric; Prins, Thomas Jay; Ruebsam, Frank; Tran, Chinh Viet; Vourloumis, Dionisios; US2008/146625; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, 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. Recommanded Product: 3-Methyl-4-nitro-1H-pyrazole

To a solution of 3-methyl-4-nitro-lH-pyrazole (20 g, 157.36 mmol), cyclopent-3- en-l-ol (15.88 g, 188.83 mmol) and PPh3 (61.91 g, 236.04 mmol) in THF (300 mL) was added D1AD (47.73 g, 236.04 mmol) at 0 C. The mixture was stirred at 25 C for 12 h. The reaction mixture was concentrated under reduced pressure to give a residue, w hich was purified by silica gel chromatography (PE:EtOAc = 50: 1 to 20: 1) to give a mixture of l-(cyclopent-3-en-l-yi)-5-methyl-4-nitro-lH-pyrazoie and 1 -(cyclopent-3-en- 1 -yl)-3-methyl-4-nitro- lH-pyrazole as a yellow oil. LCMS: RT 1.301 min, m/z = 194.1 [M+H].To a mixture of 1-cyclopent- 3-en-l-yl-5-methyl-4-nitro-pyrazole and l-cyciopent-3-en-l-yl-3-methyl-4-nitro-pyrazole (10 g, 51.76 mmol), bis [(Z)-l-methyl-3-oxo-but-l-enoxy]copper (948 mg, 3.62 mmol) in DCE (300 mL) was added a solution of ethyl 2-diazoacetate (23.6 g, 207.04 mmol) in DCE (600 mL) over a period of 12 h at 90 C. The mixture was stirred at 90 C for 4 h. The reaction mixture was concentrated under reduced pressure to give a residue, which was purified by silica gel column chromatography (PE:EtOAc :=: 20: 1 to 5: 1) to give a mixture of ethyl 3-(5-methyl-4-nitro-lH-pyrazol-l-yl)bicyclo[3.1.0]hexane-6-carboxylate and ethyl 3-(3-methy3-4~nitro-lH-pyrazol-l-yl)bicyclo[3.1.0]hexane-6~carboxy as a yellow solid. LCMS: RT 0.831 mm, m/z = 280.1 [M+H]+.

The synthetic route of 5334-39-4 has been constantly updated, and we look forward to future research findings.

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

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. 1453-58-3, name is 3-Methylpyrazole, A new synthetic method of this compound is introduced below., COA of Formula: C4H6N2

Step C. [2-Methyl-5-(3-methyl-1H-pyrazol-1-yl)-phenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone Sodium hydride (60percent suspension in oil, 0.25 g, 6.25 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (10 mL). Neat 3-methylpyrazole (0.28 mL, 3.5 mmol) was added in one portion at ambient temperature. Stirring was continued until the gas evolution subsided. The (5-fluoro-2-(methyl)-phenyl)-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone of Step B (0.75 g, 1.94 mmol) was added in one portion to the clear solution. The mixture was heated to reflux for 26 hours, cooled and partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with hexane-ethyl acetate (gradient from 8:2 to 7:3) provided the title product (0.55 g) as a pale yellow foam which was crystallized by sonication from hexane-ethanol, m.p. 209-210° 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:
Patent; American Home Products Corporation; US6235900; (2001); B1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics