Day: July 2, 2021

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. 360056-45-7, name is Methyl 4-amino-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C5H7N3O2

2,6-dichlorobenzoyl chloride (8.2 g; 39.05 mmol) was added cautiously to a solution of 4- amino-1H-pyrazole-3-carboxylic acid methyl ester (prepared in a manner analogous to 165B) (5 g; 35.5 mmol) and triethylamine (5.95 ml; 42.6 mmol) in dioxan (50 ml) then stirred at room temperature for 5 hours. The reaction mixture was filtered and the filtrate treated with methanol (50 ml) and 2M sodium hydroxide solution (100 ml), heated at 50 0C for 4 hours, and then evaporated. 100 ml of water was added to the residue then acidified with concentrated hydrochloric acid. The solid was collected by filtration, washed with water (100 ml) and sucked dry to give 10.05 g of 4-(2,6-dichloro-benzoylamino)-1H- pyrazole-3-carboxylic acid as a pale violet solid.

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; ASTEX THERAPEUTICS LIMITED; WO2008/1101; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 37622-90-5, 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. 37622-90-5, name is Ethyl 4-pyrazolecarboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

l-(Chloromethyl)-4-methoxybenzene (157 mmol, 24.5 g) and K2CO3 (39.43 g, 285.71 mmol) were added to a solution of ethyl lH-pyrazole-4- carboxylate (143 mmol, 20.0 g) in acetonitrile (150 mL). The resulting mixture was stirred under reflux for 5 h. After cooling to rt, the mixture was filtered and concentrated in vacuum. The residue was purified by flash chromatography over silica gel using EtOAc/PE ( 1 :20 to -1 :5) as eluent to afford ethyl l-(4-methoxybenzyl)-lH- pyrazole-4-carboxylate ( 126.7 mmol, 33 g, 89%) as an off-white solid. LC-MS: m/z ES = 261.

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

Reference:
Patent; ADDEX PHARMA S.A.; BOLEA, Christelle; CELANIRE, Sylvain; BOUDOU, Cedric; TANG, Lam; ROCHER, Jean-Philippe; LIVERTON, Nigel, J.; WO2012/9009; (2012); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 20154-03-4, name is 3-(Trifluoromethyl)-1H-pyrazole, 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. Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole

NaH (33.08 g (19.85, 60percent), 1.5 eq) was added to small quantity of hexane and stirred well for 10 min. Hexane was decanted, dry DMF (500 ml) was added drop wise under N2 atmosphere and stirred well. A solution of step-b product (75 g, 0.55 mol) in DMF (125 ml) was added drop wise under N2 atmosphere. Then a solution of 4-methoxylbenzoyl chloride (86.3 g, 0.55 mol, 1 eq) in DMF (125 ml) was added drop wise and the overall reaction mixture was allowed to stir for 12 hrs at RT. Progress of the reaction was monitored by TLC (10percent ethyl acetate/hexane, Rf-0.4). On completion of the reaction, reaction contents were poured into ice water (500 ml) and the product extracted with ethyl acetate (2 * 400 ml). Then the contents were dried over sodium sulfate and concentrated under reduced pressure to yield the required product as a brown colored liquid (125 g, 88percent yield).

The synthetic route of 3-(Trifluoromethyl)-1H-pyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUeNENTHAL GMBH; FRANK, Robert; BAHRENBERG, Gregor; CHRISTOPH, Thomas; SCHIENE, Klaus; DE VRY, Jean; DAMANN, Nils; FRORMANN, Sven; LESCH, Bernhard; LEE, Jeewoo; KIM, Yong-Soo; KIM, Myeon-Seop; WO2010/127856; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 181585-93-3,Some common heterocyclic compound, 181585-93-3, name is Methyl 5-nitro-1H-pyrazole-3-carboxylate, molecular formula is C5H5N3O4, 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) 5-Nitro-2-(3,4,5-trifluoro-benzyl)-2H-pyrazole-3-carboxylic acid methyl ester A mixture of methyl-3-nitro-1-H-pyrazole-5-carboxylate (ART-CHEM) (600 mg, 3.5 mmol), 3,4,5-trifluoromethylbenzyl bromide (789 mg, 3.5 mmol) and cesium carbonate (1.37 g, 4.2 mmol) in 15 ml of acetonitrile was stirred at 60 C. for 2 hours. The reaction mixture was concentrated, hydrolyzed and extracted with ethyl acetate. The organic phase was dried, evaporated and the residue triturated with diethyl ether to yield the title compound as a colorless solid (698 mg, Yield=63%). MS ISP (m/e): 333.1 (100) [(M+NH4)+]. 1H NMR (CDCl3, 300 MHz): delta (ppm)=7.43 (s, 1H), 7.04 (t, 2H), 5.75 (s, 2H), 3.95 (s, 3H).

The synthetic route of 181585-93-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Baumann, Karlheinz; Goetschi, Erwin; Jolidon, Synese; Limberg, Anja; Luebbers, Thomas; US2010/120874; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 37687-18-6, name is 1-(1-Methyl-1h-pyrazol-4-yl)-ethanone, 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. Application In Synthesis of 1-(1-Methyl-1h-pyrazol-4-yl)-ethanone

Lithium bis(trimethylsilyl)amide (1.0 M in THF, 9.5 mL, 9.5 mmol) was added to a solution of methyl 5-bromo-l-(2-trimethylsilylethoxymethyl)-l,2,4-triazole-3-carboxylate (2.0 g, 5.9 mmol) and l -(l-methylpyrazol-4-yl)ethanone (1.20 g, 9.5 mmol) in THF (40 mL) at 0C. After, the reaction was warmed to rt and stirred for 1 h. The reaction was diluted with water and isopropyl acetate. A 5% citric acid solution was added and the aqueous layer was extracted with isopropyl acetate (4 x 100 mL). The combined organic layers were dried with sodium sulfate, concentrated and the crude residue was purified by flash column chromatography (silica, 0% to 100% isopropyl acetate – heptane) to givel -[5-bromo-l -(2-trimethylsilylethoxymethyl)-l ,2,4-triazol-3-yl]-3-(l -methylpyrazol-4- yl)propane-l,3-dione (2.40 g, 5.60 mmol, 94% yield). LCMS RT = 1.57 min, m/z = 427.9 [M + H]+.

The synthetic route of 1-(1-Methyl-1h-pyrazol-4-yl)-ethanone has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; PATEL, Snahel; HAMILTON, Gregory; ZHAO, Guiling; CHEN, Huifen; DANIELS, Blake; STIVALA, Craig; (358 pag.)WO2019/12063; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 57097-81-1,Some common heterocyclic compound, 57097-81-1, name is 3-Bromo-5-methyl-1H-pyrazole, molecular formula is C4H5BrN2, 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.

INTERMEDIATE 63 4-(3-bromo-5-methyl-lH-pyrazol-l-yl)-2-(trifluoromethyl)pyrimidine To a solution of 3-bromo-5-methyl-lH-pyrazole (100 mg, 0.621 mmol) in anhydrous DMSO (2 mL) was added NaH (27.3 mg, 0.683 mmol) at 0 C. The mixture was stirred for 30 min at 0 C, followed by the addition of 4-chloro-2- (trifluoromethyl)pyrimidine (113 mg, 0.621 mmol) in DMSO (1 mL). The resulting mixture was stirred at room temperature overnight. The mixture was quenched with water (5 mL) and extracted EtOAc (10 mL x 3). The organic layer was collected and dried over Na2S04. The solvent was removed in vacuo to give the crude product. This was purified by flash chromatography (ISCO Combiflash, 10 g, Biotage Si column, ~30 mL/min, 100% hexanes 5 min, gradient to 100% EtOAc in hexanes 15 min) to afford 4-(3-bromo-5-methyl-lH-pyrazol-l-yl)-2-(trifluoromethyl)pyrimidine. LCMS calc. = 308.98; found = 308.91 (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 3-Bromo-5-methyl-1H-pyrazole, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MOCHIDA PHARMACEUTICAL CO., LTD.; SMITH, Cameron, James; TAN, John, Qiang; ZHANG, Ting; BALKOVEC, James; GREENLEE, William, John; GUO, Liangqin; XU, Jiayi; CHEN, Yi-heng; CHEN, Yili; CHACKALAMANNIL, Samuel; HIRABAYASHI, Tomokazu; NAGASUE, Hiroshi; OGAWA, Kouki; WO2014/120346; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 82560-12-1, 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. 82560-12-1 name is 3-Amino-5-tert-butylpyrazole, 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.

Intermediate A14: 3-ferf-Butyl-1 -(4-methylthiophen-2-yl)-1 H-pyrazol-5-amine.; Intermediate A14; To a sol ution of 2-iodo-4-methylthiophene (WO 2008/121666) (1 .00 g, 4.50 mmol) in anhydrous toluene (15.0 mL) was added 3-ie f-butyl-1 /-/-pyrazol-5-amine (683 mg, 4.91 mmol) followed by (1 R,2R)-/V1,/V2-dimethylcyclohexane-1 ,2-diamine (140 mu, 0.89 mmol) and potassium carbonate (1.30 g, 9.37 mmol). The mixture was purged with N2, copper(l) iodide (42 mg, 0.22 mmol) was added and the reaction mixture was heated at reflux under N2 for 16 hr during which time most of the solvent was lost. The resulting mixture was partitioned between ethyl acetate (150 mL) and water (150 mL) and the organic layer was separated and extracted with aq. citric acid solution (10% w/v, 150 mL) followed by brine (50 mL), and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, 120 g, DCM, isocratic elution) to afford the title compound, Intermediate A14, as a brown solid (340 mg, 32%); R’ 1.94 min (Method 2); m/z 236 (M+H)+ (ES+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Amino-5-tert-butylpyrazole, and friends who are interested can also refer to it.

Reference:
Patent; RESPIVERT LIMITED; MURRAY, Peter, John; ONIONS, Stuart, Thomas; WILLIAMS, Jonathan, Gareth; JOLY, Kevin; WO2011/158044; (2011); A2;,
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. 6994-25-8, name is Ethyl 3-amino-1H-pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., Computed Properties of C6H9N3O2

General procedure: After standard evacuation and back-fill cycles with argon, a Schlenk tube fitted with a magnetic stirrer bar was charged with pyrazole derivative (1.29 mmol), aryl iodide (1.1 eq), K3PO4 (2 eq) and copper iodide (0.1 eq). N,N’-dimethyl-cyclohexane-1,2-diamine (0.2 eq) and anhydrous dioxane (3 mL) were then added under a stream of argon by syringe at room temperature. The sealed tube is stirred at 110 C for 24-48 h. A 28% solution of ammonia and water are added at room temperature to the reaction mixture. The resulting aqueous layer is extracted with DCM. The combined organic layers are dried on MgSO4, filtered and evaporated under reduced pressure. The residue is triturated in an appropriate solvent or purified on silica gel.

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; Deprez-Poulain, Rebecca; Cousaert, Nicolas; Toto, Patrick; Willand, Nicolas; Deprez, Benoit; European Journal of Medicinal Chemistry; vol. 46; 9; (2011); p. 3867 – 3876;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route 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,6aS)-3-[1-allyl-5-(4-bromophenyl)-6-chloro-imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane (508.1 mg, 0.837 mmol), tert-butyl 4,6-dihydro-2H-pyrrolo[3,4-c]pyrazole-5-carboxylate (213.1 mg, 1.018 mmol), tripotassium phosphate (603.1 mg, 2.84 mmol), and copper(I) iodide (33.2 mg, 0.174 mmol). The vial was evacuated and backfilled with nitrogen (3×). Trans-N,N?-dimethylcyclohexane-1,2-diamine (53 mul, 0.335 mmol) and dioxane (1.6 ml) were added to the vial to give a pale blue suspension that was heated at 100 C. with stirring for 24 h. The reaction mixture was 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 light green residue. Flash chromatography of the residue utilizing an 40 g silica RediSep Rf column and employing a 0-40% EtOAc/hexane gradient followed by 40% EtOAc/hexane afforded the desired product as a white foam. LC-MS: calculated for C37H47ClN6O6Si 734.3 observed m/e: 735.34 (M+H)+ (Rt 1.47/2 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 2644-93-1,Some common heterocyclic compound, 2644-93-1, name is 1,3,5-Trimethyl-1H-pyrazole-4-carbaldehyde, molecular formula is C7H10N2O, 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.

General procedure: Sodium triacetoxyborohydride (46.3 mg, 0.218 mmol) was added toa mixture of 10c (65 mg, 0.146 mmol) and tetrahydropyran-4-carbaldehyde(18.3 mg, 0.160 mmol) in 1,2-dichloroethane (1.30 mL). The mixture was stirred at room temperature for 2 h, sat.NaHCO3 aqueoussolution was added, and the mixture was extracted with CHCl3. The organic layer was washed with brine, dried with Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (CHCl3/MeOH) to give the desired compound as a white solid (41.0 mg, 52%). 1H NMR (DMSO-d6) delta1.00-1.29 (3H, m), 1.44-1.60 (3H, m), 1.64-1.85 (3H, m), 1.95-2.17(5H, m), 2.62-2.71 (1H, m), 2.78-2.88 (1H, m), 3.08 (3H, s), 3.15-3.29(2H, m), 3.70-3.83 (2H, m), 4.01 (3H, s), 4.05 (3H, s), 4.27-4.37 (2H,m), 7.26 (1H, s), 8.11 (1H, s), 8.43 (1H, d, J=2.3 Hz), 8.85 (1H, d,J=2.3 Hz), 9.37 (1H, s); ESI-MS m/z 545.3 [(M+H)+]; HRMS(ESI) m/z calcd for C26H37N6O5S [(M+H)+]: 545.2541, found: 545.2537

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1,3,5-Trimethyl-1H-pyrazole-4-carbaldehyde, its application will become more common.

Reference:
Article; Hamajima, Toshihiro; Takahashi, Fumie; Kato, Koji; Sugano, Yukihito; Yamaki, Susumu; Moritomo, Ayako; Kubo, Satoshi; Nakamura, Koji; Yamagami, Kaoru; Hamakawa, Nozomu; Yokoo, Koji; Fukahori, Hidehiko; Bioorganic and Medicinal Chemistry; vol. 26; 14; (2018); p. 3917 – 3924;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics