Day: August 5, 2021

Reference of 1029413-53-3, A common heterocyclic compound, 1029413-53-3, name is tert-Butyl 3-(4-amino-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate, molecular formula is C12H20N4O2, 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 72C (1S,2S,3R,4R)-3-{[5-chloro-2-({1-[(3S)-pyrrolidin-3-yl]-1H-pyrazol-4-yl}amino)pyrimidin-4-yl]amino}bicyclo[2.2.1]hept-5-ene-2-carboxamide (+)-(1S,2S,3R,4R)-3-(2,5-Dichloropyrimidin-4-ylamino)bicyclo[2.2.1]hept-5-ene-2-carboxamide (75 mg, 0.25 mmol) and (S)-tert-butyl 3-(4-amino-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate (63 mg, 0.25 mmol) were combined with 2-propanol (2.4 ml) in a sealed tube and the mixture was heated to 85 C. for 4 hours. The reaction mixture was concentrated to dryness, then treated with 5 mL TFA and stirred for 15 minutes. The mixture was again concentrated to dryness, the residue was dissolved in CH2Cl2, and the mixture was treated with aqueous saturated NaHCO3. The layers were separated and the aqueous layer was further extracted 3* with ethyl acetate. The extracts were dried (Na2SO4) and concentrated, then purified by flash chromatography yielding the desired product. 1H NMR (300 MHz, DMSO-D6) ppm 1.41 (d, J=7.8 Hz, 1H) 1.92-2.04 (m, 1H) 2.07-2.21 (m, 2H) 2.52-2.56 (m, 1H) 2.71-2.91 (m, 3H) 2.93 (d, J=5.4 Hz, 1H) 2.95-3.03 (m, 1H) 3.12 (dd, J=11.5, 7.12 Hz, 1H) 4.13 (t, J=7.5 Hz, 1H) 4.65-4.77 (m, 1H) 6.25-6.40 (m, 2H) 7.25 (s, 1H) 7.51 (s, 1H) 7.61-7.84 (m, 3H) 7.89 (s, 1H) 9.10 (s, 1H); MS (ESI(+)) m/e 415 (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; Abbott Laboratories; US2010/317680; (2010); 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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, A new synthetic method of this compound is introduced below., Computed Properties of C4H3N3

To a solution of compound F5 (150 mg, 0.329 mmol) in acetone (5 mL) was added K2C03 (68.1 mg, 0.493 mmol) and 1 H-pyrazole-4-carbonitrile (45.8 mg, 0.493 mmol). After stirring at 25 C for 3 h, LCMS showed the reaction was complete. The reaction mixture was filtered, and the filtrate was concentrated in vacuum to give the crude product (150 mg). The crude product was purified by prep. HPLC (HC1) to give the desired product 170 (13 mg, 8.41%) as white solid. 1H NMR (170) (yield 8.4%): (400 MHz, CDC13) delta 7.86(s,lH), 7.81 (s, 1H), 5.03-4.87 (m, 2H), 3.54(d, J= 9.2Hz, 1H), 3.68-3.41 (m, 2H), 3.24 (d, J= 9.2Hz,lH), 2.59 (t, J= 9.2Hz, lH), 2.21- 1.15 (m, 29H), 0.65 (s, 3H). LCMS tR = 0.949 min in 1.5 min chromatography, 5-95AB, purity 98.6%, MS ESI calcd. for C28H42 3O3 [M+H]+ 467, found 450[M+H-18]+.

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

Reference:
Patent; SAGE THERAPEUTICS, INC.; MARTINEZ BOTELLA, Gabriel; HARRISON, Boyd, L.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, Gerald; HERR, Robert, Jason; KARGBO, Robert, Borbo; WO2015/27227; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 612511-81-6, These common heterocyclic compound, 612511-81-6, name is (1-Methyl-1H-pyrazol-3-yl)methanamine, 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 4-fluoro-N-methyl-3-nitrobenzamide (350 mg, 1 .766 mmol) in DMF (5 mL) were added (1 -methyl-1 H-pyrazol-3-yl)methanamine (206 mg, 1 .855 mmol) and K2C03 (317 mg, 2.296 mmol), and the reaction mixture was stirred at room temperature overnight. The reaction was then quenched with water (10 mL), and the resulting solid was isolated by filtration, washed with water, and dried in vacuum oven for 4 hours to afford N-methyl-4-(((1 -methyl- 1 H-pyrazol-3-yl)methyl)amino)-3-nitrobenzamide (390 mg) as an orange color solid. LC-MS (ES) m/z = 290 [M+H]+. NMR (400 MHz, DMSO-d6): delta 2.76 (d, J = 4.3 Hz, 3H), 3.81 (s, 3 ), 4.57 (d, J = 5.3 Hz, 2H), 6.19 (d, J = 2.0 Hz, 1 H), 7.15 (d, J = 9.1 Hz, 1 H), 7.64 (d, J = 2.3 Hz, 1 H), 7.96 (dd, J = 9.0, 2.2 Hz, 1 H), 8.46 (d, J = 4.8 Hz, 1 H), 8.63 (d, J = 2.3 Hz, 1 H), 8.77 (t, J = 5.6 Hz, 1 H).

The synthetic route of 612511-81-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; MEDINA, Jesus Raul; TIAN, Xinrong; NG DI MARCO, Christina; GRAYBILL, Todd L.; HEERDING, Dirk A.; LI, William Hoi Hong; MANGATT, Biju; MARTYR, Cuthbert D.; RIVERO, Raphael Anthony; (570 pag.)WO2019/49061; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 5203-77-0, name is 1,3-Dimethyl-1H-pyrazol-5-ol, 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 5203-77-0, SDS of cas: 5203-77-0

Intermediate 9 (4 mmol), dissolved in dry dichloromethane( 60 mL), and DCC (4.8 mmol) were mixed together and stirred at room temperature for 1 h. Then 1,3-dimethyl-1H-pyrazol-5-ol (4 mmol) and DMAP (0.4 mmol) were added to the above solution,and stirred for a further 24-36 h at room temperature. After adding dichloromethane (30 mL), the resultant mixture was washed sequentially with 2 N hydrochloric acid (100 mL), saturated NaHCO3 and saturated brine and dried over anhydrous sodium sulfate.The residue solution was evaporated in vacuum and purified by silica gel column chromatography using gradient elution of ethyl acetate/hexane (V/V = 1/2) to obtain the desired intermediate 10.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,3-Dimethyl-1H-pyrazol-5-ol, and friends who are interested can also refer to it.

Reference:
Article; Xu, Yu-Ling; Lin, Hong-Yan; Cao, Run-Jie; Ming, Ze-Zhong; Yang, Wen-Chao; Yang, Guang-Fu; Bioorganic and Medicinal Chemistry; vol. 22; 19; (2014); p. 5194 – 5211;,
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. 25016-11-9, name is 1-Methyl-1H-pyrazole-4-carbaldehyde, A new synthetic method of this compound is introduced below., Safety of 1-Methyl-1H-pyrazole-4-carbaldehyde

To a solution of ethyl 2-(diethoxyphosphoryl)acetate (5.4 g, 22.7 mmol, 1 eq) in THF (100 mL) at 0C was added sodium hydride (60 % in mineral oil, 1.2 g, 29.5 mmol, 1.3 eq)portion-wise and the mixture was allowed to stir at the same temperature for 30 minutes. To this mixture was added a solution of 1-methyl-1H-pyrazole-4-carbaldehyde (2.5 g, 22.7 mmol, 1.0 eq) in THF (10 mL) and the resulting mixture was allowed to stir at 0 C for 1 h. Progress of reaction was monitored by TLC. After completion, reaction mixture was diluted with saturated aq. NH4C1 (100 mL) and extracted with ethyl acetate (3 x 100 mL). Combined organic layer waswashed with brine, dried over anhydrous Na2SO4 and evaporated to dryness under vacuum to afford ethyl (E)-3-(1-methyl-1H-pyrazol-4-yl)acrylate (3.9 g, 95 %) which was used in the next step without further purification.

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; AURANSA INC.; PROTTER, Andrew, Asher; GREEN, Michael, John; CHANG, Hak, Jin; PHAM, Son, Minh; CHAKRAVARTY, Sarvajit; LUEDTKE, Gregory, R.; (254 pag.)WO2019/103897; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 632365-54-9,Some common heterocyclic compound, 632365-54-9, name is Methyl 5-amino-1H-pyrazole-3-carboxylate, molecular formula is C5H7N3O2, 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 stirred solution of 1-15d (450 mg, 1.50 mmol) in EtOH (30 mL) was added methyl 5-amino- 1H-pyrazole-3-carboxylate (450 mg, 1.90 mmol) at rt. The reaction mixture was heated at 85 C for 4 h, then concentrated under reduced pressure. The afforded crude was purified by column chromatography on silica gel, eluted with 20% ethyl acetate / pet ether which gave the title compound (300 mg) as a solid with 65% LCMS purity.MS (ES+) m/z 372.33 [M+H]+. The compound was used in next step without further purification.

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

Reference:
Patent; MEDIVIR AKTIEBOLAG; ERSMARK, Karolina; KARLSTROeM, Sofia; KLASSON, Bjoern; LUNDGREN, Stina; ROSENQUIST, Asa; SALVADOR ODEN, Lourdes; (155 pag.)WO2018/226150; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 176969-34-9, 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. 176969-34-9, name is 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

In a 50 mL eggplant-shaped bottle, add 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (0.707 g, 4.01 mmol), add dichloromethane (20 mL), and add oxalyl chloride (1.29 g , 9.96mmol), add 1 drop of N, N-dimethylformamide dropwise, stir at reflux at room temperature, you can clearly see that the reaction solution gradually changed from turbid to clear, TLC followed the reaction, and the reaction ended after 1 hour. The solvent was spin-dried to obtain Intermediate 1, which was dissolved again with dichloromethane (10 mL) and set aside.

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-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; East China University of Science and Technology; Shao Xusheng; Li Zhong; Fu Wen; Cheng Jiagao; Xu Xiaoyong; Xu Zhiping; (43 pag.)CN111087345; (2020); 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. 25016-20-0, name is 1-Methyl-1H-pyrazole-3-carboxylic acid, A new synthetic method of this compound is introduced below., HPLC of Formula: C5H6N2O2

The 1-methyl-1 H-pyrazole-3-carboxylic acid R2a (16 mg, 0.127 mmol, 1 .2 equiv) is dissolved in DMF (2 mL), then TEA (59.1 muIota_, 0.442 mmol, 4 equiv) followed by TBTU (39.2 mg, 0.127 mmol, 1.2 equiv). The reaction mixture is stirred for 15 mins, after which the amine hydrochloride Dc is added in DMF (1 mL). The resulting solution is stirred at RT for 16 h. The solution is then filtered through a Millex filter and purified by prep HPLC. (ammonium bicarbonate/MeOH). The pure fractions are combined, concentrated, frozen and lyophilized to provide compound 1016.FIA M.S.(electrospray) : 808.3 (M-H)- , 810.3 (M+H)+ Retention time (min): 5.4 min1H NMR (400 MHz,DMSO-d6): delta 1 .04 (s, 1 H) , 8.76 (s, 1 H), 7.83-7.80 (m, 2H), 7.76 (d, 1 H, J = 2.0Hz), 7.24 (d, 1 H, J = 7.8Hz), 6.59 (d, 1 H, J = 2.3Hz), 6.45 (s, 1 H), 5.70-5.55 (m, 1H), 5.49-5.43 (p, 1H, J= 6.3Hz), 5.43 (s, 1H), 5.2-5.07 (m, 1H), 4.70-4.50 (m,1H), 4.49-4.40 (m, 1H), 4.39-4.25(m, 1H), 4.03-3.85 (m, 1H), 3.95 (s, 3H), 3.89 (s, 3H), 2.95-2.80 (m, 1H), 2.65-2.55 (m, 1H), 2.35-2.19 (m, 2H), 2.0-1.85 (m, 1H), 1.84-1.66 (m, 1H), 1.65-1.5 (m, 3H); 1.49-1.15 (m, 14H); 1.14-0.94 (m, 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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; LLINAS-BRUNET, Montse; BORDELEAU , Josee; GODBOUT, Cedrickx; LEBLANC, Melissa; MOREAU, Benoit; O’MEARA, Jeffrey; WO2011/63501; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 1226781-82-3, name is tert-Butyl 2-(methylsulfonyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, 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 1226781-82-3, name: tert-Butyl 2-(methylsulfonyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate

To the product from Step C (87 g, 303 mmol) in isopropyl acetate (1 L) was added benzensulfonic acid (71.8 g, 454 mmol) and the mixture warmed to 40 C and stirred for 2 h. The mixture was cooled to ambient temperature and stirred for 16 h to give an off-white slurry. The solid was filtered, washed with isopropyl acetate, and suction dried to afford the title compound as a white solid. LC MS: 188.1 (M+l).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; HICKS, Jacqueline, D.; BIFTU, Tesfaye; CHEN, Ping; QIAN, Xiaoxia; WILKENING, Robert, R.; WO2011/146358; (2011); 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. 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., Quality Control of 1-Methyl-4-nitro-1H-pyrazole

General procedure: To a 8 mL glass vial equipped with a magnetic stirbar were sequentially added K2CO3 (207 mg, 1.5 mmol), the nitroazole substrate (0.50 mmol), aryl halide (0.50 mmol oras indicated), toluene (0.50 M or 1.0 M), Pd(OAc)2 (5.60mg, 0.025 mmol) and [PCy3H]BF4 (18.4 mg, 0.050 mmol).The reaction mixture was purged with nitrogen through aTeflon-lined cap. Then the cap was replaced with a newTeflon-lined solid cap. The reaction vial was moved to a preheatedreaction block. After stirring for 18 h at the indicatedtemperature, the reaction mixture was cooled to 25 C and concentrated. The residue was purified by flash column chromatography to provide the desired arylated 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; Jung, Haeun; Bae, Seri; Jang, Ha-Lim; Joo, Jung Min; Bulletin of the Korean Chemical Society; vol. 35; 10; (2014); p. 3009 – 3014;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics