Tag: M.W:200-300

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 500011-84-7 as follows. SDS of cas: 500011-84-7

Step B: Preparation of 3-BromopyrazoleTo trifluoroacetic acid (70 mL) was slowly added the bromopyrazole product (57.04 g) from Step A. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated at reduced pressure. The residue was taken up in hexane, insoluble solids were filtered off, and the hexane was evaporated to afford the crude product as an oil. The crude product was further purified by chromatography on silica gel using ethyl acetate/dichloromethane (10:90) as eluent to afford an oil. The oil was taken up in dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with methylene chloride (3×), dried over magnesium sulfate and concentrated to afford the title product as a white solid (25.9 g), m.p. 61-64 C. 1H NMR (CDCl3) delta 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H).

According to the analysis of related databases, 500011-84-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; E I DU PONT DE NEMOURS AND COMPANY; Lahm, George Philip; McCann, Stephen Frederick; Patel, Kanu Maganbhai; Selby, Thomas Paul; Stevenson, Thomas Martin; US9113630; (2015); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 398495-65-3, name is 5-tert-Butyl 1-ethyl 3-aminopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate, 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 398495-65-3, Product Details of 398495-65-3

General procedure: To a solution of 2 (13.00 g, 43.90 mmol) and DIEA ( 33.60 g, 260.00 mmol) in dry THF (400 mL) was added dropwise a solution of corresponding acyl chlorides (48.30 mmol) in dry THF (50 mL) over a period of 1 h at room temperature. The reaction mixture was stirred for 12 h at the same temperature and concentrated under reduced pressure. The residue was treated with ethyl acetate / saturated saline (400 mL: 400 mL) and stayed for 2 h, and then filtered. The precipitate was washed with diethyl ether (30 mL), and dried in vacuo to yield the title compounds 3a-d. 3e was obtained by flash chromatography (180 g silica gel, petroleum ether/AcOEt, 0-30%, V/V).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-tert-Butyl 1-ethyl 3-aminopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate, and friends who are interested can also refer to it.

Reference:
Article; Bai, Xiao-Guang; Yu, Dong-Ke; Wang, Ju-Xian; Zhang, Hao; He, Hong-Wei; Shao, Rong-Guang; Wang, Yu-Cheng; Li, Xue-Mei; Bioorganic and medicinal chemistry letters; vol. 22; 22; (2012); p. 6947 – 6951,5;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 18048-64-1, These common heterocyclic compound, 18048-64-1, name is 1-(3,4-Dimethylphenyl)-3-methyl-1H-pyrazol-5(4H)-one, 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 8; 3- {N’-[ 1 -(3,4-Dimethyl-phenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]- hydrazino)-biphenyl-2,3′-dicarboxylic acid (Compound 108) was prepared as described in Scheme II. ¹H NMR (500 MHz, Acetone-d6) 8 8.10-8.06 (m, 2H), 7.77-7.68 (m, 4H), 7.60 (t, J= 7.6 Hz, 1H), 7.30 (dd, J= 7.8, 1.0 Hz, 1H), 7.19 (d, J= 8.3 Hz, 1H), 2.36 (s, 3H), 2.30 (s, 3H), 2.26 (s, 3H).

The synthetic route of 18048-64-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LIGAND PHARMACEUTICALS INC.; WO2005/118551; (2005); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 155377-19-8, These common heterocyclic compound, 155377-19-8, name is Ethyl 3-(trifluoromethyl)pyrazole-4-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.

Example 118: Preparation of l-allyl-S-trifluoromethyl-lH-pyrazole^-carboxylic acid ethyl ester and 2-allyl-3-trifluoromethyl-2Hl-pyrazole-4-carboxylic acid ethyl ester3-Trifluoromethyl-lH-pyrazole-4-carboxylic acid ethyl ester (500 mg, 2.4 mmol) was dissolved in acetone and stirred. To the solution was added potassium carbonate(498 mg, 3.6 mmol), in one portion, followed by dropwise addition of allyl bromide (0.31 ml, 3.6 mmol). The reaction mixture was stirred at room temperature for 5 hours. The reaction mixture was poured into water and extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulfate and concentrated to give a 9:1 mixture of l-allyl-3-trifluoromethyl-l//-pyrazole-4-carboxylic acid ethyl ester (isomer A) and 2-allyl-3-trifluoromethyl-2H-pyrazole-4-carboxylic acid ethyl ester (isomer B) (557 mg, 93% yield) as a yellow solid. Isomer A (major isomer) 1H-NMR (400 MHz, CDCl3): 1.39 (t, 3H, Me), 4.35 (q, 2H, CH2), 4.8 (d, 2H, CH2), 5.3-5.45 (dd, 2H, CH2), 6.05 (m, IH, CH), 8.01 (s, IH, CH) ppm. Isomer B (minor isomer) 1H-NMR (400 MHz, CDCl3): 1.39 (t, 3H, Me), 4.35 (q, 2H, CH2), 4.95 (d, 2H, CH2), 5.1-5.3 (dd, 2H, CH2), 6.05 (m, IH, CH), 7.98 (s, IH, CH) ppm.

Statistics shows that Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate is playing an increasingly important role. we look forward to future research findings about 155377-19-8.

Reference:
Patent; SYNGENTA LIMITED; WO2007/71900; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 3528-45-8, 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. 3528-45-8, name is 1-(4-Methoxybenzyl)-1H-pyrazol-5-amine belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A stirred mixture of triethoxymethane (339 mL, 2037 mmol), and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) (35.2 g, 244 mmol) was heated to 80 C. for 1 hour. A suspension of 1-(4-methoxybenzyl)-1H-pyrazol-5-amine [41.4 g, 204 mmol; prepared according to the procedure described by Misra, R. N., et al. Bioorg. Med. Chem. Lett. 2003, 13, 1133-1136, except desalting was performed as follows: 1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride (44 g) was partitioned between MTBE (300 mL) and 1N aqueous NaOH (300 mL), after separating the phases, the aqueous suspension was re-extracted with MTBE (8×100 mL), followed by drying (Na2SO4) the combined organic phases, and concentration in vacuo to obtain the free-based 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (30 g)] in triethoxymethane (339 mL, 2037 mmol) was added at once and heating at 80 C. was continued for 18 hours under N2. After cooling to room temperature, toluene azeotrope (2×200 mL) was utilized to remove EtOH. The resulting suspension was diluted with diethyl ether (500 mL) and filtered to obtain a yellow solid (33.5 g, 46%). 1H NMR (400 MHz, CDCl3) delta 11.13 (d, J=13 Hz, 1H), 8.26 (d, J=13 Hz, 1H), 7.50 (d, J=2 Hz, 1H), 7.25 (d, J=9 Hz, 2H), 6.88 (d, J=9 Hz, 2H), 6.21 (d, J=2 Hz, 1H), 5.28 (s, 2H), 3.78 (s, 3H), 1.74 (s, 6H).

The synthetic route of 1-(4-Methoxybenzyl)-1H-pyrazol-5-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Blake, James F.; Boyd, Steven Armen; De Meese, Jason; Fong, Kin Chiu; Gaudino, John J.; Kaplan, Tomas; Marlow, Allison L.; Seo, Jeongbeob; Thomas, Allen A.; Tian, Hongqi; Cohen, Frederick; Young, Wendy B.; US2007/238726; (2007); A1;,
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. 741717-63-5, name is Ethyl 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 741717-63-5

A mixture of 1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (160 mg, 0.56 mmol) and 1N aqueous sodium hydroxide solution (2.3 mL, 2.3 mmol) in methanol (10 mL) was stirred at room temperature overnight. The reaction mixture was acidified to pH2 with 1N aqueous hydrochloric acid and concentrated to give 1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid as an off-white solid, which was directly used without further purification. LCMS calcd for C11H7F3N2O (m/e) 256, obsd 257 (M+H).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 741717-63-5.

Reference:
Patent; Bolin, David Robert; Cheung, Adrian Wai-Hing; Firooznia, Fariborz; Hamilton, Matthew Michael; Li, Shiming; McDermott, Lee Apostle; Qian, Yimin; Yun, Weiya; US2007/123504; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 10250-64-3, These common heterocyclic compound, 10250-64-3, name is 1-Methyl-3-phenyl-1H-pyrazole-5-carboxylic acid, 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.

General procedure: To a solution of 19 (1.2 eq) and HOBt(1.4 eq) in DMF (0.5 M) were added EDCI (1.3 eq) and a solution of 15a-j or 16a-j (1.0 eq) in DMF (0.25 M), Et3N (3.5 eq) at 0 C. The reaction mixture was stirred at room temperature for 24 hours, then diluted in AcOEt. The organic phase was washed with water twice, saturated aqueous NaHCO3 three times, and brine, then dried over Na2SO4,filtered, and concentrated. The residue was purified by flash column chromatography to give intermediates 17a-j and 18a-j.

The synthetic route of 10250-64-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 25; 23; (2015); p. 5619 – 5624;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 50877-42-4, 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. 50877-42-4, name is 1-Benzyl-4-iodo-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 1-benzyl-4-iodo-1H-pyrazole (1.05 g, 3.70 mmol) , bis (pinacolato) diboron (1.00 g, 3.94 mmol) , potassium acetate (1.00 g, 9.88 mmol) and Pd (dppf) Cl2(130 mg, 0.18 mmol) in DMSO (20 mL) was stirred at 80 under N2for 7 h. The reaction mixture was cooled to rt and quenched with water (50 mL) . The resulting mixture was extracted with EtOAc (50 mL × 3) . The combined organic layers were washed with saturated aqueous NaCl (50 mL × 2) , dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 5/1 to give a light yellow oily product (200 mg, 19.0) .[1088]MS (ESI, pos. ion) m/z: 282.3 [M+1]+ and[1089]1H NMR (600 MHz, CDCl3) : delta (ppm) 7.84 (s, 1H) , 7.69 (s, 1H) , 7.34 (m, 3H) , 7.25 (m, 2H) , 5.32 (s, 2H) , 1.32 (s, 12H)

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, 1-Benzyl-4-iodo-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; LIU, Bing; ZHANG, Yingjun; CHENG, Changchung; HUANG, Jiuzhong; BAI, Shun; REN, Xingye; LI, Zhi; ZHOU, Youbai; (368 pag.)WO2016/615; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 39806-90-1,Some common heterocyclic compound, 39806-90-1, name is 4-Iodo-1-methyl-1H-pyrazole, molecular formula is C4H5IN2, 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.

Step 1: A clean and dry 500 L glass-lined reactor A was evacuated to -0.08–0.O5MPa and filled with nitrogen to normal pressure. It was repeated for 3 times. The reactors were sampled for oxygen content to ensure it was 3%.[001145j Diisopropylamine (106.0 kg) and 1-methyl-4-iodo-1H-pyrazole (24.3 kg, 23.6 kg corrected) were added to the reactor A at 15-25 C. Cuprous iodide (0.37 kg) was added to reactor A under the protection of nitrogen at 15-25 C. Bis(triphenylphosphine)palladium(II) chloride (1.09 kg) was added to the mixture under the protection of nitrogen at 15-25 C. The mixture was stirred for 20-30 mi Trimethylsilylacetylene (22.2 kg, 14.0 kg corrected) was added to the mixture in portions with 4-5 kg and an interval of 20-30 mm for each portion at 15-30 C. The mixture was allowed to react at 20-30 C. After 2h, the mixture was sampled every 1-2h for purity analysis by HPLC until area% of 1-methyl-4-iodo-1H-pyrazole was 0.5%.[001 146j After reaction completion, the mixture was filtered with a stainless steel centrifuge. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). The filtrate was transferred to reactor A and concentrated under reduced pressure (P -0.08 MPa) at T 45 C until 40-60 L was left. Methyl tert-butyl ether (92.5 kg) was added to the mixture and concentration was continued until 40-60 L was left. Methyl tert-butyl ether (92.2 kg) was added to concentrated mixture and the mixture was sampled for diisopropylamine residual analysis to ensure it was 1%. Active carbon (4.9 kg) was added to the mixture at 15-25 C and the mixture was maintained for 6-8 h under stirring. The mixture was filtered with stainless steel nutsche filter at 15-25 C. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). A solution of citric acid monohydrate (6.1 kg) in purified water (121.6 kg) was added to the filtrate at 15-25 C. The mixture was stirred for 20-30 mm and settled for 20-3 0 mm before separation. The emulsion layer was separated to aqueous phase. The aqueous phase was sampled for pH analysis and wt% analysis to ensure pH was < 7. Active carbon (4.9 kg) was added to the mixture at 15-25 C and the mixture was maintained for 6-8 h under stirring. The mixture was filtered with stainless steel nutsche filter at 15-25 C. The filter cake was rinsed twice with methyl tert-butyl ether (9.2 kg x2). The filtrate was checked to ensure it was yellow solution. The filtrate was transferred to reactor B and concentrated under reduced pressure (P -0.O8MPa) at T 35 C until 30-40 L was left. Anhydrous ethanol (96.3 kg) was added to the mixture and concentration was continued at T 45 C until 30-40 L was left. The mixture was sampled for methyl tert-butyl ether residual analysis to ensure it was 0.5%. The mixture was cooled to 15-25 C. Purified water (121.3 kg) was added to the mixture through peristaltic pump at 15-25 C at a reference rate of 25-50 kg/h. Brown yellow solid precipitated. The mixture was allowed to crystallize at 15-25 C. After 2h, the mixture was sampled every 1- 2h for mother liquor wt% analysis until it was 0.5% or the difference between the two samples was 0.3%. The mixture was filtered with a stainless steel nutsche filter. The filter cake was rinsed twice with purified water (12.1 kg x2). The filter cake was swept in the stainless steel nutsche filter. After 12h, the solid was sampled every 6-8h for ethanol residual until it was 1%. The product was packaged in one plastic bag. Product weight12.0 kg, Yield = 52.3%, Purity (HPLC) = 98.9%. These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Iodo-1-methyl-1H-pyrazole, its application will become more common. Reference:
Patent; INFINITY PHARMACEUTICALS, INC.; CRENIER, Louis; LESCARBEAU, Andre; SHARMA, Praveen; GENOV, Daniel G.; (324 pag.)WO2017/48702; (2017); A1;,
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