Day: May 18, 2021

Synthetic Route of 821767-61-7,Some common heterocyclic compound, 821767-61-7, name is tert-Butyl 4-formyl-1H-pyrazole-1-carboxylate, molecular formula is C9H12N2O3, 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 methyl 2-(((benzyloxy)carbonyl)amino)-2- (dimethoxyphosphoryl)acetate (101 mg, 0.306 mmol) in DCM (1 mL) was added DBU (0.042 mL, 0.280 mmol). The reaction mixture was stirred for 10 minutes under Ar at room temperature. A solution of /er/-butyl 4-formyl-li/-pyrazole-l-carboxylate (50 mg, 0.255 mmol) in DCM (0.5 mL) was added to the reaction mixture. The reaction mixture was stirred at room temperature under Ar for 1 h. The mixture was concentrated and purified by flash chromatography to give Example 5B (76 mg, 74%). LCMS (ES): m/z 402.2 [M+H]+.

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; ZHAO, Guohua; DEVASTHALE, Pratik; YE, Xiang-Yang; SELVAKUMAR, Kumaravel; DHANUSU, Suresh; BALASUBRAMANIAN, Palanikumar; GUERNON, Leatte R.; CIVIELLO, Rita; HAN, Xiaojun; PARKER, Michael F.; JACUTIN-PORTE, Swanee E.; (290 pag.)WO2018/89353; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 1031351-95-7, name is Methyl 3-formyl-1-methyl-1H-pyrazole-5-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 C7H8N2O3

To a solution of methyl 3-formyl-1-methyl-1H-pyrazole-5-carboxylate (Bellen Chem;1 g, 5.95 mmol) in CH2Cl2 (30 mL) at 0 C was added bis-(2-methoxyethyl)aminosulfur- trifluoride (3.29 mL, 17.8 mmol) in CH2Cl2 (5 mL) dropwise via syringe pump over 40 minutes. The mixture was allowed to stir at 0 C for 20 minutes, then the ice-bath was removed, and the mixture was allowed to warm to ambient temperature. The mixture was then allowed to stir for an additional 90 minutes and was quenched by slow addition of saturated, aqueous NaHCO3 (25 mL) added via syringe pump over 1 hour. The mixture was diluted with CH2Cl2 (15 mL), then the layers were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 7 mL). The combined organic fractions were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified via column chromatography (SiO2, 50% ethyl acetate/heptanes) to give the title compound (1.01 g, 5.31 mmol, 89% yield). MS (ESI+) m/z 191 (M+H)+.

The synthetic route of Methyl 3-formyl-1-methyl-1H-pyrazole-5-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CALICO LIFE SCIENCES; ABBVIE, INC.; SIDRAUSKI, Carmela; PLIUSCHEV, Marina; FROST, Jennifer, M.; BLACK, Lawrence, A.; XU, Xiangdong; SWEIS, Ramzi, Farah; SHI, Lei; ZHANG, Qinwei, I.; TONG, Yunsong; HUTCHINS, Charles, W.; CHUNG, Seungwon; DART, Michael, J.; (661 pag.)WO2017/193063; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3273-44-7, 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 3273-44-7 as follows.

General procedure: To a suspension of 5-methyl-1H-pyrazole-3-carbaldehyde (18; 2-6 equiv) in anhydrous THF (10 mL) (in the case of the synthesis of 1) or MeOH (in the case of the synthesis of 2-5 and 11), the corresponding derivative bearing one to three amino groups (17,21 25-289d,11 or 36,4c see Scheme 1 and Scheme 2) (1 equiv), dissolved in anhydrous MeOH (5 mL), was added. The resulting mixture was heated at reflux until a clear solution resulted and then stirred at r.t. (up to 4 days, TLC analysis). The resulting imines were reduced without further purification by addition of NaBH4 (3-9 equiv) in portions. After complete addition of the reducing agent, the reaction mixture was stirred for 24 h at r.t. and then the solvent was removed under reduced pressure. The residue was suspended in CHCl3-H2O (1:1, 10 mL) and stirred for 12 h at r.t. The resulting suspension was extracted with CHCl3 (3 × 20 mL), dried over MgSO4, and the solvent was removed. The crude product was purified by column chromatography.

According to the analysis of related databases, 3273-44-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Koch, Niklas; Seichter, Wilhelm; Mazik, Monika; Synthesis; vol. 48; 17; (2016); p. 2757 – 2767;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

75092-30-7, name is 4-Iodo-1-methyl-1H-pyrazole-5-carboxylic acid, 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. Safety of 4-Iodo-1-methyl-1H-pyrazole-5-carboxylic acid

Step 1. 4-[(4-Benzylphenyl)amino]-1-methyl-1H-pyrazole-5-carboxylic acid A mixture of 4-iodo-1-methyl-1H-pyrazole-5-carboxylic acid ((Manaev, Yu. A. et al., J. Gen. Chem. USSR (Engl. Transl.), 1982, 52 (11), 2291), 8.0 g, 31.74 mmol), 4-benzylaniline (21.03 g, 114.76 mmol) and copper powder (3.2 g) in a mixture of 5% aqueous sodium carbonate (160 ml) and dimethylsulfoxide (80 ml) was stirred for 17 h at 100 C. After cooling to room temperature, the mixture was filtered through a pad of Celite, which was washed with water, 2N aqueous sodium hydroxide and diethyl ether. The separated water layer was washed with diethyl ether (100 ml*2). The water layer was acidified with concentrated hydrochloric acid and the formed solid was collected by filtration, dried, to give 4.86 g (50%) of the pure title compound as a pale brown solid. Rf value: 0.50 (methanol/dichloromethane/acetic acid=1/10/2 drops). 1H-NMR (DMSO-d6) delta: 7.63 (1 H, s), 7.50 (1 H, br s), 7.31-6.96 (9 H, m), 4.00 (3 H, s), 3.85 (2 H, s). One signal was not observed.

The synthetic route of 75092-30-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Kawamura, Kiyoshi; Mihara, Sachiko; Nukui, Seiji; Uchida, Chikara; US2003/130277; (2003); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 25700-12-3, 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. 25700-12-3 name is 3-(1H-Pyrazol-1-yl)pyridine, 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 a mixture of 3-(1H-pyrazol-1-yl)pyridine (5 g, 34.4 mmol), iodic acid (1.212 g, 6.89 mmol), and iodine (3.50 g, 13.78 mmol) in acetic acid (49.2 ml) was added sulfuric acid (0.918 ml, 17.22 mmol). The reaction mixture heated to 70 C. for 30 min. The reaction mixture was poured onto ice water, extracted with Et2O and then was washed with sodium thiosulfate solution. The organics were then dried with MgSO4, filtered and concentrated in vacuo. The residue purified by flash chromatography eluting with 0-50% acetone in dichloromethane to yielded a light tan solid (6.1 g, 21.38 mmol, 62.1% yield): mp 145-146 C.; 1H NMR (400 MHz, acetone-d6) delta 9.11 (d, J=2.3 Hz, 1H), 8.60 (d, J=0.5 Hz, 1H), 8.56 (dd, J=4.7, 1.4 Hz, 1H), 8.22 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.84 (s, 1H), 7.54 (ddd, J=8.3, 4.7, 0.7 Hz, 1H); EIMS m/z 271.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(1H-Pyrazol-1-yl)pyridine, and friends who are interested can also refer to it.

Reference:
Patent; DOW AGROSCIENCES LLC; Lowe, Christian T.; Trullinger, Tony K.; Hunter, Ricky; US2012/220453; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 54006-63-2, 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. 54006-63-2, name is 5-(4-Chlorophenyl)-1H-pyrazole-3-carboxylic acid belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

General procedure: To amixture of 3-(3-chlorophenyl)-1H-pyrazole-5-carboxylic acid (14a, 133 mg, 0.60 mmol) inDMF(4 mL)was added (S)-methyl-4-(2-amino-3-phenylpropanamido)benzoate hydrochloride (12, 200 mg,0.60 mmol), N,N-diisopropyl-ethylamine (232 mg, 1.80 mmol), 1-hydroxybenzotriazole(161 mg,1.20 mmol) and N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride (229 mg, 1.20 mmol)and the reaction mixture was stirred at room temperature overnight.Then TLC analysis indicatedreaction was complete, and H2O (40 mL) was added.The mixture was stirred for 10 min and filtered toget crude product 13a as a yellow solid, which was used for next step without further purification.

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, 5-(4-Chlorophenyl)-1H-pyrazole-3-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Wei, Qunchao; Zheng, Zhichao; Zhang, Shijun; Zheng, Xuemin; Meng, Fancui; Yuan, Jing; Xu, Yongnan; Huang, Changjiang; Molecules; vol. 23; 8; (2018);,
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. 3273-44-7, name is 5-Methyl-1H-pyrazole-3-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., name: 5-Methyl-1H-pyrazole-3-carbaldehyde

General procedure: To a suspension of 5-methyl-1H-pyrazole-3-carbaldehyde (18; 2-6 equiv) in anhydrous THF (10 mL) (in the case of the synthesis of 1) or MeOH (in the case of the synthesis of 2-5 and 11), the corresponding derivative bearing one to three amino groups (17,21 25-289d,11 or 36,4c see Scheme 1 and Scheme 2) (1 equiv), dissolved in anhydrous MeOH (5 mL), was added. The resulting mixture was heated at reflux until a clear solution resulted and then stirred at r.t. (up to 4 days, TLC analysis). The resulting imines were reduced without further purification by addition of NaBH4 (3-9 equiv) in portions. After complete addition of the reducing agent, the reaction mixture was stirred for 24 h at r.t. and then the solvent was removed under reduced pressure. The residue was suspended in CHCl3-H2O (1:1, 10 mL) and stirred for 12 h at r.t. The resulting suspension was extracted with CHCl3 (3 × 20 mL), dried over MgSO4, and the solvent was removed. The crude product was purified by column chromatography.

According to the analysis of related databases, 3273-44-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Koch, Niklas; Seichter, Wilhelm; Mazik, Monika; Synthesis; vol. 48; 17; (2016); p. 2757 – 2767;,
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. 2654-57-1, name is 4-Methyl-1-phenylpyrazolidin-3-one, A new synthetic method of this compound is introduced below., Quality Control of 4-Methyl-1-phenylpyrazolidin-3-one

General procedure: 1a (0.5?mmol), Pd(OAc)2 (5?mol%), AMS (20?mol%), K2CO3 (0.4 equiv.), and dry chlorobenzene (1?mL) were added in a test tube. The reaction mixture was allowed to stir vigorously at 110?C for 6?h. After cooling at room temperature, the mixture was concentrated and the residue was purified by column chromatography on Al2O3 (mobile phase: dichloromethane/methanol or petroleum ether/ethyl acetate) to afford the pure 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; Zhu, Ye-Fu; Wei, Bo-Le; Wei, Jiao-Jiao; Wang, Wen-Qiong; Song, Wei-Bin; Xuan, Li-Jiang; Tetrahedron Letters; vol. 60; 17; (2019); p. 1202 – 1205;,
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 6647-93-4 as follows. category: pyrazoles-derivatives

A suspension of 4-iodo- 1 H-pyrazole-3-carboxylic acid Compound la(500 mg, 2.101 mmol), 4-methoxy-benzene-l ,2-diamine dihydrochloride (443 mg, 2.101 mmol), HATU (799 mg, 2.101 mmol), and diisopropyl ethylamine (815 mg, 6.303 mmol) in 15 ml DMF was stirred at 50 C for 16 hrs. After cooled to rt, the mixture was diluted with 150 ml EtOAc, washed with water (7 times) and brine, then dried with Na2SO4. Evaporation give 4-iodo- 1 H-pyrazole-3-carboxylic acid (2-amino-5-methoxy-phenyl)-amide Compound Ib (615 mg, 81.7 %) as a yellowish powder. NMR (DMSO): delta 3.70 (s, 3H), 6.20 (m, IH), 6.46 (s, H), 7.12 (d, J=8.0 Hz, IH), 8.10 (s, IH). MS m/z 358 (MH+).

According to the analysis of related databases, 6647-93-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN PHARMACEUTICA N.V.; WO2008/48502; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1904-24-1,Some common heterocyclic compound, 1904-24-1, name is 3-Amino-5-ethylpyrazole, 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.

Method 79; 6-Ethyl-2-chloro-4- (5-ethyl-lH-pvrazol-3-ylamino) pyrimidine 2,4-Dichloro-6-ethyl-pyrimidine (J. Am. Chem. Soc. 1936, 58, 78) (1.33g 7.53mmol) was stirred in ethanol (50ml) and 5-ethyl-lH-3-amino-pyrazole (Method 6 of WO 03/048133) (0. 836g, 7.53mmol) was added followed by sodium carbonate (1.25g) and the mixture stirred at 40C for 4 days then at 55C overnight. The insoluble inorganics were removed by filtration and solvent removed from the filtrate by evaporation. Water (100ml) was added and the mixture extracted with EtOAc (3 x 50ml). The extracts were combined and washed with water (50ml), brine (50ml), dried (MgS04) and solvent removed by evaporation. The residue was purified by column chromatography on silica gel eluting with hexane/EtOAc (100: 0 increasing in polarity to 0: 100) to give the title compound (210mg, 11%) a white solid. NMR (DMSO-d6 at 100C) : 1.20 (m, 6H), 2.50-2. 70 (m, 4H), 6.05 (s, 1H), 7.05 (br s, 1H), 9.70 (br s, 1H), 11.85 (br s, 1H) ; m/z 252 [MH] +.

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

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/40159; (2005); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics