Day: July 2, 2021

Some common heterocyclic compound, 64517-88-0, name is 1,3-Dimethyl-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. Safety of 1,3-Dimethyl-1H-pyrazol-4-amine

[7]; DMA was used as the reaction solvent. The reaction product was purified by trituration in a saturated aqueous sodium bicarbonate solution. The resultant solid was isolated, washed with water and dried under vacuum. The product gave the following characterising data :- 1HNMR Spectrum: (DMSOd6) 1.45 (t, 3H), 2.12 (s, 3H)5 3.69 (s, 3H)5 3.81 (s, 3H)5 3.84 (q, 2H)5 4.29 (q5 2H), 6.84 (d, IH), 7.46 (d, IH)5 7.79 (d, IH)5 7.81 s, IH), 8.03 (d, IH), 8.73 (s, IH)5 8.74 (d, IH)5 9.52 (s, IH); Mass Spectrum: M+H+ 449.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 64517-88-0, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/113548; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 718632-46-3, 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. 718632-46-3, name is 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 9.70 g (61.3 mmol) of 1-(trimethylsilyl)cyclopropanecarboxylic acid [synthesized according to the method described in J. Org. Chem., 1982 (47) 5, 893-895] in 120 ml of dehydrated dichloromethane, 6.60 ml (76.9 mmol) of oxalyl chloride and 0.25 ml (3.2 mmol) of dehydrated DMF were added in this order at 0C in a nitrogen atmosphere and then stirred for 2.5 hours with the temperature unchanged. After the completion of the reaction, the reaction solution was concentrated under reduced pressure and dried under reduced pressure to obtain a concentration residue. To a solution of 19.0 ml (109 mmol) of DIPEA and 9.94 g (30.6 mmol) of 5-tert-butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate [synthesized according to the method described in Journal of Medicinal Chemistry 2012, 55 (10), 4728-4739] in 170 ml of dehydrated dichloromethane, a solution of the obtained concentration residue in 30 ml of dehydrated dichloromethane was added at 0C in a nitrogen atmosphere and then stirred for 24 hours with the temperature unchanged. After the completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added to the reaction solution and stirred, followed by extraction with dichloromethane once and ethyl acetate twice. All of the obtained organic layers were dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to silica gel column chromatography (elution solvent: n-hexane:ethyl acetate = 90:10 to 70:30 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure. A concentration residue of a fraction containing impurities was subjected again to silica gel column chromatography (elution solvent: n-hexane:ethyl acetate = 90:10 to 75:25 (V/V)), combined with the purified form obtained above, concentrated under reduced pressure, and dried under reduced pressure to obtain 10.63 g of a concentration residue. To a solution of the obtained concentration residue in 100 ml of ethyl acetate, 60.0 ml (240 mmol) of 4 N hydrogen chloride/ethyl acetate was added at room temperature in a nitrogen atmosphere and then stirred for 5 hours with the temperature unchanged. After the completion of the reaction, the reaction solution was concentrated under reduced pressure. The obtained concentration residue was suspended in diisopropyl ether, and the suspension was stirred at room temperature. Insoluble matter was collected by filtration, and the obtained solid was washed with diisopropyl ether. The obtained solid was dissolved in water, and then, a saturated aqueous solution of sodium bicarbonate and dichloromethane were added and stirred at room temperature for 5 minutes. After separation into an aqueous layer and an organic layer, the aqueous layer was subjected to extraction with dichloromethane twice. All of the organic layers were washed with a saturated aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and dried under reduced pressure to obtain 8.27 g of the title compound (yield: 73% [2 steps]) as a light orange solid. Mass spectrum (DUIS, m/z): 365 [M+1]+. 1H-NMR spectrum (400 MHz, CDCl3) delta: 10.02 (s, 1H), 4.53 (q, J = 7.2 Hz, 2H), 4.16 (s, 2H), 1.50 – 1.43 (m, 9H), 1.14 – 1.08 (m, 2H), 0.84 – 0.77 (m, 2H), 0.12 (s, 9H).

The chemical industry reduces the impact on the environment during synthesis 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Ube Industries, Ltd.; AGA, Yasuhiro; USHIYAMA, Shigeru; IWASE, Noriaki; KONO, Shigeyuki; SUNAMOTO, Hidetoshi; MATSUSHITA, Takashi; OGI, Sayaka; TANAKA, Masayuki; MATOYAMA, Masaaki; UMEZAKI, Satoshi; SHIRAISHI, Yusuke; ONUMA, Kazuhiro; KOJIMA, Masahiro; NISHIYAMA, Hayato; KIMURA, Tomio; (481 pag.)EP3214086; (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. 39806-90-1, name is 4-Iodo-1-methyl-1H-pyrazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 4-Iodo-1-methyl-1H-pyrazole

To a solution of 4-amino- 1 -methyl -pyrrolidin-2-one (100 mg, 0.88 mmol) in toluene (2 ml) was added 4-iodo- 1 -methyl-pyrazole (200 mg, 0.96 mmol), sodium tert-butoxide (168 mg, 1.75 mmol) and [2-(2-aminoethyl)phenyl]-chloro-palladium;ditert-butyl-[2- (2,4,6- triisopropylphenyl)phenyl]phosphane (also known as tBuXPhos Pd Gl) (60 mg, 88 pmol), then the mixture was stirred at 100 C for 3 h. The mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 5pm 150×30; mobile phase: [water (0.1 % TFA) – ACN]; B: 1 – 30 %,l0 min) to give the title compound as colourless gum (Y = 20 %). ‘H NMR (400 MHz, methanol-*) d ppm 7.63 (s, 1H), 7.43 (s, 1H), 4.17 – 4.05 (m, 1H), 3.87 (s, 3H), 3.84 – 3.76 (m, 1H), 3.43 (dd, J= 3, 11 Hz, 1H), 2.90 – 2.79 (m, 4H), 2.41 (dd, j= 3, 18 Hz, 1H).

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; NODTHERA LIMITED; HARRISON, David; WATT, Alan Paul; BOCK, Mark G.; (334 pag.)WO2019/121691; (2019); 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. 1310350-99-2, name is 4-Chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 4-Chloro-1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid

A solution of 4-chloro-1-difluoromethyl-1H-pyrazole-3-carboxylic acid (150 mg, 0.76 mmole) in dichloromethane (5 ml) was subsequently treated at 22 C. with N,O-dimethylhydroxylamine hydrochloride (78 mg, 0.80 mmole), N-methylmorpholine (0.09 ml, 0.8 mmole) and EDCI.HCl (154 mg, 0.8 mmole) and stirring was continued for 16 h. The mixture was washed with 1 M aqueous HCl and H2O, the organic layer was dried, evaporated and the residue purified by chromatography on silica gel using cyclohexane/AcOEt (2:1) to give the title compound (164 mg) as a colorless oil. MS: m/z=240.1 [M]+.

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; Banner, David; Gabellieri, Emanuele; Guba, Wolfgang; Hilpert, Hans; Hornsperger, Benoit; Humm, Roland; Mauser, Harald; Mayweg, Alexander V.; Narquizian, Robert; Pinard, Emmanuel; Rogers-Evans, Mark; Woltering, Thomas; Wostl, Wolfgang; US2012/35195; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 4149-06-8, 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. 4149-06-8, name is 3-Amino-1-phenyl-1H-pyrazol-5(4H)-one, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: The mixture of isatin (1 mmol), 3-amino-1-phenyl-1H-pyrazol-5(4H)-one (1 mmol), 1,2-diarylethan-1-one, 2,3-dihydroinden-1-one (1 mmol) or 3,4-dihydronaphthalen-1(2H)-one (1 mmol), H2O (6 mL), HOAc (2 mL) was put in a reaction flask under 90 C about 5-7 h (monitored by TLC). After completion, the reaction mixture was cooled to room temperature and the products would be isolated out at same time. Then, compound 4 was recrystallized from DMF, however, the pure products of 6 and 8 were filtered from water, dried, without further recrystallization.

The chemical industry reduces the impact on the environment during synthesis 3-Amino-1-phenyl-1H-pyrazol-5(4H)-one. I believe this compound will play a more active role in future production and life.

Reference:
Article; Wang, Zhansheng; Gao, Lingli; Xu, Zhongyun; Ling, Zhi; Qin, Yaqi; Rong, Liangce; Tu, Shu-Jiang; Tetrahedron; vol. 73; 4; (2017); p. 385 – 394;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 16617-46-2,Some common heterocyclic compound, 16617-46-2, name is 3-Amino-1H-pyrazole-4-carbonitrile, molecular formula is C4H4N4, 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.

5-Amino-1H-pyrazole-4-carbonitrile (1) (5 g, 0.046 mol) was added to cooled concentrated sulphuric acid (10 ml) with stirring sothat the temperature did not rise above 20 °C. The addition took about one-half hour and solution was stirred at room temperaturefor 4 h. The acid solution was then poured with stirring into ice and the solution was kept overnight in the refrigerator. The solid was then filtered and washed with water to free of excess sulphuric acid to afford the desired product 5-amino-1H-pyrazole-4-carboxylic acid amide (2) as white solid; (5.19 g, 89percent); mp 220-222 °C (Lit.mp 222-225 °C) [33].

The synthetic route of 16617-46-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Singla, Prinka; Luxami, Vijay; Singh, Raja; Tandon, Vibha; Paul, Kamaldeep; European Journal of Medicinal Chemistry; vol. 126; (2017); p. 24 – 35;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 2644-93-1, name is 1,3,5-Trimethyl-1H-pyrazole-4-carbaldehyde, 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. category: pyrazoles-derivatives

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.37 g, 3.86 mmol, Intermediate 10: step d) was added THF (45 mL) at room temperature which resulted in a colorless homogeneous mixture. The solution was cooled to -78 C. and then n-BuLi (2.5 M in hexanes, 1.8 mL, 4.5 mmol) was added dropwise. The color of the solution became a reddish-brown color. After 4 minutes, 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (300 mg, 2.17 mmol, in 3 mL THF) was introduced and the color of the mixture changed from reddish-brown to a yellow-greenish color over 5 minutes. The mixture was allowed to warm to 0 C. over 45 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The mixture was diluted further with water and extracted with EtOAc (3*150 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give a light orange foam. FCC on silica gel (2% MeOH-DCM increasing to 8% MeOH-DCM) afforded the title compound as a light yellow amorphous solid. 1H NMR (500 MHz, CDCl3) delta ppm 8.23 (s, 1H), 7.78 (d, J=8.6 Hz, 1H), 7.56-7.47 (m, 3H), 7.40 (d, J=8.1 Hz, 2H), 6.01 (d, J=3.0 Hz, 1H), 4.35 (s, 2H), 4.06 (s, 3H), 3.70 (s, 3H), 2.14 (s, 3H), 2.12 (s, 3H), 2.09 (d, J=3.3 Hz, 1H). MS (ESI): mass calcd. for C25H23ClF3N3O2, 489.1; m/z found, 490.1 [M+H]+.

The synthetic route of 1,3,5-Trimethyl-1H-pyrazole-4-carbaldehyde has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, KRISTI A.; BARBAY, KENT; EDWARDS, JAMES P.; KREUTTER, KEVIN D.; KUMMER, DAVID A.; MAHAROOF, UMAR; NISHIMURA, RACHEL; URBANSKI, MAUD; VENKATESAN, HARIHARAN; WANG, AIHUA; WOLIN, RONALD L.; WOODS, CRAIG R.; FOURIE, ANNE; XUE, XIAOHUA; CUMMINGS, MAXWELL D.; US2015/105372; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 16034-46-1,Some common heterocyclic compound, 16034-46-1, name is 1-Methyl-1H-pyrazole-5-carboxylic acid, molecular formula is C5H6N2O2, 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 1-methyl-1H-pyrazole-5-carboxylic acid (compound 4A, 4.07 g, 32.2 mmol), DIEA (12.2 g, 94.1 mmol) in CH2Cl2 (30 mL) was added EDCI (10.3 g, 53.7 mmol) and DMAP (3.94 g, 32.2 mmol) at -5 C., the mixture was stirred at -5 C. for 30 min under N2. Then 4-bromo-2-methylaniline (compound 7, 5.00 g, 26.9 mmol) was added, the mixture was stirred at -5 C. for 30 min, then warmed to 25 C., stirred for 11 hrs. TLC (petroleum ether:ethyl acetate=1:1, Rf=0.27) showed one new point formed. The mixture was concentrated in vacuum to give light yellow oil. The oil was purified by silica gel column chromatography (petroleum ether: ethyl acetate=80:20 to 50:50) to give N-(4-bromo-2-methylphenyl)-1-methyl-1H-pyrazole-5-carboxamide (compound 8, 6.40 g, 81% yield) as light yellow solid. 1H NMR (400 MHz, CDCl3) delta delta ppm 7.72 (d, J=8.2 Hz, 1H), 7.47-7.58 (m, 2H), 7.33-7.41 (m, 2H), 6.64 (s, 1H), 4.20 (s, 3H), 2.28 (s, 3H); ES-LCMS m/z 294.1 [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 1-Methyl-1H-pyrazole-5-carboxylic acid, its application will become more common.

Reference:
Patent; Kyn Therapeutics; Castro, Alfredo C.; Evans, Catherine Anne; (108 pag.)US2019/55218; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 1280210-79-8,Some common heterocyclic compound, 1280210-79-8, name is tert-Butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, molecular formula is C10H15N3O2, 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.

A vial was charged with (3R,3aR,6R,6aR)-6-[5-(4-bromophenyl)-6-chloro-1-(2-trimethylsilylethoxymethyl)-imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (501.8 mg, 0.861 mmol), tert-butyl 4,6-dihydro-2H-pyrrolo[3,4-c]pyrazole-5-carboxylate (240.3 mg, 1.148 mmol), tripotassium phosphate (581.6 mg, 2.74 mmol), and copper(I) iodide (37.2 mg, 0.195 mmol). The reaction was evacuated (3×) and backfilled with nitrogen. Trans-N,N?-dimethylcyclohexane-1,2-diamine (55 mul, 0.348 mmol) and dioxane (1.7 ml) were added to the vial to give a hazy suspension, which was heated to 100 C. for 24 h. The reaction mixture was then cooled to room temperature and partitioned between EtOAc (100 ml) and water (100 ml). The aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×30 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a pale green residue. Flash chromatography of the residue utilizing a 40 g silica RediSep Rf column and employing a 0-100% EtOAc/hexane gradient afforded a mixture of the two pyrazole linked regioisomers as a pale amber foam. LC-MS: calculated for C34H43ClN6O7Si 710.27 observed m/e: 711.29 (M+H)+ (Rt 1.30/2 min)

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 4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate, its application will become more common.

Reference:
Patent; APGAR, James M.; ARASAPPAN, Ashok; BIFTU, Tesfaye; CHEN, Ping; FENG, Danqing; GUIDRY, Erin; HICKS, Jacqueline; KEKEC, Ahmet; LEAVITT, Kenneth; LI, Bing; MCCRACKEN, Troy; SEBHAT, Iyassu; QIAN, Xiaoxia; WEI, Lan; WILKENING, Robert; WU, Zhicai; Merck Sharp & Dohme Corp.; Apgar, James M.; Arasappan, Ashok; Biftu, Tesfaye; Chen, Ping; Feng, Danqing; Guidry, Erin; Hicks, Jacqueline D.; Kekec, Ahmet; Leavitt, Kenneth J.; Li, Bing; McCracken, Troy; Sebhat, Iyassu; Qian, Xiaoxia; Wei, Lan; Wilkening, Robert R.; Wu, Zhicai; US2015/284411; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 1613191-73-3, 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 1613191-73-3 as follows.

Step 2: 2-amino- 7-(tert-butoxycarbonyl)-5, 6, 7, 8-tetrahydropyrazolo[ 1, 5-a]pyrido[ 4, 3- dJpyrimidine-3-carboxyiic acid 5 [00269] A mixture of tert-butyl 3-(l,3-dioxolan-2-yl)-4-oxo-piperidine-l-carboxylate (4.3 g, 15.85 mmol), allyl 3,5-diamino-lH-pyrazole-4-carboxylate 3 (2.888 g, 15.85 mmol), KOH (215.1 mg, 3.833 mmol) in dioxane (86 mL) was stirred at RT for 18 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in DCM (50 mL). Phenylsilane (1.715 g, 1.953 mL, 15.85 mmol) and palladium triphenylphosphane (549.5 mg, 0.4755 mmol) were added to the reaction mixture which was stirred at RT for 4 h. The precipitate was filtered off and washed with DCM yielding 2-amino-7-(tert-butoxycarbonyl)-5,6,7,8- tetrahydropyrazolo[l,5-a]pyrido[4,3-d]pyrimidine-3-carboxylic acid 5 as a beige solid which was used in next step without further purification. MS (ES+) 334.1.

According to the analysis of related databases, 1613191-73-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DAVIS, Chris; DURRANT, Steven; JARDI, Gorka, Etxebarria I; FRAYSSE, Damien; KAY, David; KNEGTEL, Ronald; PIERARD, Francoise; PINDER, Joanne; STORCK, Pierre-Henri; WO2014/143240; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics