Category: pyrazoles-derivatives

Electric Literature of 14521-80-3, 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. 14521-80-3, name is 3-Bromo-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 3-bromopyrazole (1.00 g, 6.8 mmol) in ethyl ether (20 mL) was treated with 37% formaldehyde (0.3 mL, 4.0 mmol). The obtained solution was set aside at room temperature overnight. The volatiles were evaporated under reduced pressure. Toluene (5 mL) was added, and the evaporation was repeated. The obtained oil was triturated with ethyl ether (3 mL) to crystallize. The crystals were separated by decantation and dried to give 3-bromo-l- (hydroxymethyl)pyrazole (371 mg, 37%). A suspension of the obtained product in chloroform (5 mL) was treated with thionyl chloride (0.5 mL) and heated at reflux for 1 h. The volatiles were removed under reduced pressure to provide crude 3-bromo-l-(chloromethyl)pyrazole. A suspension of the unsubstituted triazinone from Example 38 (100 mg, 0.41 mmol) in DMF (3 mL) was treated with 60% NaH (18 mg, 0.45 mmol) followed by 3-bromo-l- (chloromethyl)pyrazole (82 mg, 0.49 mmol). After stirring for 1 h at room temperature, the solvent was evaporated under reduced pressure, and the residue was chromatographed (chloroform/ethyl acetate, 1 : 1). The obtained material was recrystallized from ethanol (5 mL) to give the desired product, 70 mg, MP: 180-1810C. 1H NMR (CDCl3) delta 2.03 (1 H, m), 2.19 (1 H, m), 2.35 (1 H, m), 2.53 (1 H, m), 3.70 (1 H, m), 3.91 (1 H, dt, J = 12.3 and 7.2 Hz), 5.61 (1 H, t, J = 6.0 Hz), 6.55 ( 1 H, d, J = 13.8 Hz), 6.60 (1 H, d, J = 13.5 Hz), 7.51 (1 H, s), 7.85 (1 H, s), 7.87 (1 H, s), and 8.77 (1 H, s).

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

Reference:
Patent; CORTEX PHARMACEUTICALS, INC.; WO2008/85505; (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. 138907-68-3, name is Ethyl 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., Application In Synthesis of Ethyl 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate

Intermediate 9; 5-Amiotano-1-(4-fluorophenyl)-1 /-/-pyrazole-4-carboxyliotac acid; To a suspension of ethyl 5-amiotano-1-(4-fluorophenyl)-1 /-/-pyrazole-4-carboxylate (12 1g, 48 5mmol) in ethanol (250ml) was added a solution of lithium hydroxide (5 8g, 242mmol) in water (100ml) The mixture was stirred at reflux for 2 5 hours It was allowed to cool and concentrated to 50% of its volume before 5M hydrochloric acid (47ml) was added. After stirring for 15 minutes, the resulting white solid was filtered off and further 5M hydrochloric acid (3ml) was added to the filtrate and the resulting solid was filtered and the combined solids were washed with water and diethyl ether and then dried under vacuum to give the title compound (10.27g).1H NMR (400 MHz, DMSOd6) delta ppm 12.09 (br. s., 1 H) 7.67 (s, 1 H) 7.54 – 7.60 (m, 2H) 7.34 – 7.41 (m, 2H) 6.29 (br. s., 2H). LC-MS Retention Time 2.20mins, MH+ 222.

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; GLAXO GROUP LIMITED; WO2008/777; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 876343-24-7,Some common heterocyclic compound, 876343-24-7, name is 1-Ethyl-1H-pyrazol-4-amine, molecular formula is C5H9N3, 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]; 2-(6-Chlorobenzotriazol- 1 -yl)- 1 , 1 ,3,3-tetramethyluronium tetrafluoroborate was used in place of 2-(7-azabenzotriazol-l-yl)-l,l53,3-tetramethyluronium hexafluorophosphate(V) as the coupling agent. The product gave the following characterising data :- 1H NMR Spectrum: (DMSOd6) 1.32 (t, 3H), 3.61 (s, 2H), 3.77 (s, 3H), 4.07 (q, 2H), 6.76 (d, IH), 6.92 (m, IH), 7.06 (d, IH), 7.38 (d, IH), 7.42 (s, IH)5 7.88 (s, IH), 8.08 (s, IH), 8.92 (d, IH), 9.57 (s, IH), 10.05 (s, IH); Mass Spectrum: M+H+ 438 and 440.

The synthetic route of 876343-24-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/113565; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 1192-21-8, 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. 1192-21-8 name is 1-Methyl-1H-pyrazol-5-amine, 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.

To the solution containing the amine compound (A-1), 700 mL of methanol was added. While stirring the obtained solution at an internal temperature of 5 ° C., To this solution, 120 g of an 85percent by mass aqueous solution of phosphoric acid (H 3 PO 4) (1.0 mol as H 3 PO 4) was added dropwise. By dropwise addition, Crystals precipitated. Precipitated crystals were collected by filtration, 111 g of crystals (slightly yellow to white crystals) of the organic amine salt (I-beta-2) were obtained (yield 57percent).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Methyl-1H-pyrazol-5-amine, and friends who are interested can also refer to it.

Reference:
Patent; FUJIFILM Corporation; Mikoshiba, Atsushi; (36 pag.)JP2017/19914; (2017); A;,
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. 141573-95-7, name is Ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., Formula: C8H10F2N2O2

ethyl 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate containing 0.2 area%, Purity 96.6 area% of ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate 10.0 g (0.05 mol), toluene 94 g, water 15.2 g, 25 wt% sodium hydroxide aqueous solution 1.8 g (0.07 mol) were added to the 200ml round-bottomed flask, while stirring it was heated in an oil bath and reacted under reflux for 23 hours. After cooling to room temperature, 15 mass% hydrochloric acid 21.0 g (0.09 mol) was dropped from the dropping funnel. After dropping, after cooling for 1 hour in an ice-water bath, using a 5C filter paper, suction filtered through a Kiriyama funnel, the filtrate was washed with 2 volumes of cold water. The obtained filtrate was dried under reduced pressure at 80 C. for 4 hours and got 8.60 g of crystals. When this crystal was analyzed by HPLC, it was 3- (difluoromethyl) -1-methyl -1H- pyrazole-4-carboxylic acid : 99.2 area %, 5- (difluoromethyl) -1-methyl-1 H-pyrazole-4-carboxylic acid : 0.1 area %. The toluene layer obtained by separating the filtrate into two layers, after concentrated in an evaporator, dried under reduced pressure at 80 C for 4 hours, got 0.02 g of crystals. When this crystal analyzed by HPLC, it was 3- (difluoromethyl) -1-methyl -1H- pyrazole-4-carboxylic acid : 27.2 area %, 5- (difluoromethyl) -1-methyl-1 H-pyrazole-4- carboxylic acid: 15.0 area %.

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; CENTRAL GLASS COMPANY LIMITED; IMURA, HIDEAKI; TAKADA, NAOTO; (11 pag.)JP5830957; (2015); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 35100-92-6,Some common heterocyclic compound, 35100-92-6, name is 1,5-Dimethyl-1H-pyrazol-3-amine, molecular formula is C5H9N3, 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 9 Preparation of N-(1,5-dimethylpyrazol-3-yl)-2,6 dimethyl benzamide (compound 3) To a cooled (0-5 C.) solution of 3-amino-1,5-dimethyl pyrazole (95%, 32.7 g, 0.28M) in anhydrous CH2 Cl2 (200 ml) was added a CH2 Cl2 (100 ml) solution of the 2,6 dimethyl benzoyl chloride (23.6 g, 0.14M). The reaction mixture was allowed to room temperature for 18 hours and then CH2 Cl2 was concentrated to give an oily mixture which was diluted in AcOEt. This suspension was then treated with saturated NaHCO3. After usual work-up, the crude material was cristallized with diisopropyloxide to give 13 g of the desired amide (38%: yield based on the 2,6-dimethyl benzoyl chloride). m.p.: 184 C.

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

Reference:
Patent; Novapharme; US5464860; (1995); A;,
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. 863548-52-1, name is (1-Methyl-1H-pyrazol-5-yl)methanamine, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

Step a. To a mixture of tert-butyl 2-chloro-4-(3-(2-oxopyrrolidin-l-yl)phenyl)-5,7-dihydro-6H- pyrrolo[3,4-d]pyrimidine-6-carboxylate (prepared as in step a of Example 289, 0.450 g, 1.086 mmol) and l-methyl-lH-pyrazol-5-yl)methylamine (CAS Number 863548-52-1; 0.180 g, 1.629 mmol) in 1,4-dioxane (100 ml) was added K2C03 (0.450 g, 3.258 mmol) at rt. The reaction mixture was degassed for 10 min before addition of Pd2(dba)3 (0.099 g, 0.108 mmol) and Xanthphos (0.062 g, 0.108 mmol). The reaction mixture was heated at 90C for 16 h. The resulting mixture was cooled to rt, poured into water (20 ml) and extracted with EtOAc (3 x 30 ml). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (3.2% MeOH in DCM) yielding tert-butyl 2-(((l-methyl-lH-pyrazol-5- yl)memyl)amino)-4-(3-(2-oxopyrrolidin-l-yl)phenyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6- carboxylate (0.250 g, 0.511 mmol). LCMS: Method A, 1.858 min, MS: ES+ 490.41.

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; MISSION THERAPEUTICS LIMITED; GIBSON, Karl Richard; JONES, Alison; KEMP, Mark Ian; MADIN, Andrew; STOCKLEY, Martin Lee; WHITLOCK, Gavin Alistair; WOODROW, Michael D; (241 pag.)WO2017/158388; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 25016-20-0, name is 1-Methyl-1H-pyrazole-3-carboxylic acid, 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 25016-20-0, Product Details of 25016-20-0

1-methyl-1H-pyrazole-5-carboxylic acid (35 mg, 0.28 mmol, 1.1 equiv.), HATU (109 mg, 0.29 mmol,1.15equiv.), DIPEA (37mg, 0.29mmol, 1.15equiv.) is dissolved in an appropriate amount of DMF, stirred for 10 minutes and then added (4-fluoro-2-(Trifluoromethyl)phenyl)(5-aminoindolin-1-yl)methanone (81 mg, 0.25 mmol, 1.0 equiv.), stirring at room temperature for 8 hoursTime. The TLC monitors the reaction in real time. After the reaction, dilute with water, extract the appropriate amount of ethyl acetate three times, combine the organic phase, and then use water,The mixture was washed with saturated NaHCO3 solution and saturated NaCl solution, and the organic layer was dried over anhydrous NaSO?Purification afforded N-(1-(4-fluoro-2-(trifluoromethyl)benzoyl)indolin-5-yl)-1-methyl-1H-pyrazole-3-carboxamide(80 mg, yield: 74%).

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

Reference:
Patent; Fudan University; Wang Yonghui; Yu Fazhi; Li Wei; (38 pag.)CN109232358; (2019); A;,
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. 92525-10-5, name is 3-Iodo-1-methyl-1H-pyrazole, A new synthetic method of this compound is introduced below., COA of Formula: C4H5IN2

A degassed solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one (27 mg, 0.100 mmol), 3-iodo-1-methyl-1H-pyrazole (20 mg, 0.097 mmol), N1,N2-dimethylethane-1,2-diamine (5 mg, 0.049 mmol), copper iodide (4 mg, 0.020 mmol), and potassium phosphate (43 mg, 0.197 mmol) 2 mL of N-methylpyrrolidone was heated to 70 C. After allowing the reaction to stir overnight (17 h) at 70 C., the reaction was complete and allowed to cool to room temperature. The reaction was extracted 3X’s with EtOAc (3*5 mL) and 2X’s with NaHCO3 (3*10 mL). The crude organic layers were combined, dried over anhydrous Na2SO4 (s), filtered and then concentrated in vacuo. The crude mixture was then purified using the ISCO flash chromatography system using a 0-100% EtOAc/100-0% Hexane gradient mixture. A second column was done on the impure product using a gradient of MeOH/CHCl3 after which, the appropriate fractions were concentrated, to afford a yellow solid (17 mg, 52%). 1H NMR (DMSO) delta: 8.01 (s, 1H), 7.79 (d, J=6.0, 1H), 6.34 (d, J=6.0, 1H), 6.24 (m, 1H), 6.15 (d, J=7.0 Hz, 2H), 4.00 (br. S, 2H), 3.22 (s, 2H), 2.64 (t, j=5.3 Hz, 2H), 2.20 (s, 3H)

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; Allergan, Inc.; Wurster, Julie; Yee, Richard; Hull III, Clarence Eugene; Malone, Thomas C.; (39 pag.)US2016/96832; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

34605-66-8, name is 3-(2,5-Dimethyl-1H-pyrrol-1-yl)-1-methyl-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. name: 3-(2,5-Dimethyl-1H-pyrrol-1-yl)-1-methyl-1H-pyrazole

To 3-(2,5-Dimethyl-pyrrol-1-yl)-1-methyl-1H-pyrazole (4.5 g, 25.71 mmol) in dry THF (40 ml) at -78 C. was added n-BuLi (1.7M, 16.4 ml, 28.02 mmol). The reaction mixture was stirred for 2 h at -78 C. before CNBr (2.97 g, 28.02 mmol) dissolved in THF (5 ml) was added. The mixture was allowed to warm to rt, and stirred for an additional 2 h, after which ice-water was added and the aqueous mixture extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated and purified by column chromatography to give 5-Bromo-3-(2,5-dimethyl-pyrrol-1-yl)-1-methyl-1H-pyrazole (4.4 g, 68%).

The synthetic route of 34605-66-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Alam, Muzaffar; Du Bois, Daisy Joe; Hawley, Ronald Charles; Kennedy-Smith, Joshua; Minatti, Ana Elena; Palmer, Wylie Solang; Silva, Tania; Wilhelm, Robert Stephen; US2011/71150; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics