Month: June 2021

Reference of 133228-21-4,Some common heterocyclic compound, 133228-21-4, name is N,N-Dimethyl-1H-pyrazole-1-sulfonamide, molecular formula is C5H9N3O2S, 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 A: Preparation of 3~bromo-N,N-dimethyl-lH-pyrazole-l-sulfonamide; To a solution of N,N-dimethylsulfamoylpyrazole (44.O g, 0.251 mol) in dry tetrahydrofuran (500 mL) at -78 0C was added dropwise a solution of n-butyllithium (2.5 M in hexane, 105.5 mL, 0.264 mol) while maintaining the temperature below -60 C. A thick solid formed during the addition. Upon completion of the addition the reaction mixture was stirred at -78 C for an additional 15 minutes, after which time a solution of 1,2-dibromo- tetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150 mL) was added dropwise while maintaining the temperature below -70 0C. The reaction mixture turned a clear orange; stirring was continued for an additional 15 minutes. The -78 0C bath was removed and the reaction was quenched with water (600 mL). The reaction mixture was extracted with methylene chloride (4x), and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride-hexane (50:50) as eluent to afford 57.04 g of the title product as clear colorless oil. 1H NuMR (CDCl3): delta 7.62 (m,lH), 6.44 (m,lH), 3.07 (d,6H).

The synthetic route of 133228-21-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; E.I. DUPONT DE NEMOURS AND COMPANY; WO2006/68669; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 25711-30-2,Some common heterocyclic compound, 25711-30-2, name is 1,5-Dimethyl-1H-pyrazole-4-carbaldehyde, molecular formula is C6H8N2O, 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: Synthesis of 2-substituted 5,7-dialkyl-1,3-diazaadamantanes 2-11 (General method). Substituted pyrazolecarbaldehyde (5 mmol) was added to a solution of 1,5-dialkyl-3,7-diazabicyclo[3.3.1]nonan-9-one 1a,c,d or 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ol (1b, 5 mmol) inEtOH (20 ml), and the mixture heated under reflux for 10-15 h. The solvent was evaporated, and the residue treatedwith water. The formed precipitate was filtered off andrecrystallized from hexane.

The synthetic route of 25711-30-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Gevorkyan, Qnarik A.; Arutyunyan, Amalia D.; Arutyunyan, Gayane L.; Gasparyan, Sahak P.; Danagulyan, Gevorg G.; Chemistry of Heterocyclic Compounds; vol. 53; 2; (2017); p. 192 – 195; Khim. Geterotsikl. Soedin.; vol. 53; 2; (2017); p. 192 – 195,4;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 360056-45-7, name is Methyl 4-amino-1H-pyrazole-3-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 360056-45-7, category: pyrazoles-derivatives

Stage 3: Preparation of 4-(2,6-dichlorobenzoylamino)-lH-pyrazole-3-carboxylic acid methyl ester C5H7N3O2 C7H3CI3O C12H9CI2N3O3 FW: 141.13 FW: 209.46 FW: 314.13Triethylamine (1.42L, 10.20 MoI, 1.2 vol) was added to solution of 4-amino-lH”- pyrazole-3-carboxylic acid methyl ester (1.184Kg, 8.39 MoI5 1.0 wt) in 1,4-dioxane (10.66L, 9.0 vol) at 15 to 25C under nitrogen. 2,6-Dichlorobenzoyl chloride (1.33L, 9.28 MoI, 1.12 vol) was charged at 15 to 250C followed by a line rinse of 1,4-dioxane (1.18L, 1.0 vol) and the reaction mixture stirred at 15 to 250C for 14 to 24 hours. Reaction completion was determined by 1HNMR analysis1. The reaction mixture was filtered, the filter-cake washed with 1,4-dioxane (2x 1.18L, 2x 1.0 vol) and the combined filtrates progressed to Stage 4 without further isolation.

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, Methyl 4-amino-1H-pyrazole-3-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; WO2007/129066; (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. 187998-35-2, name is 1-(4-Chlorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 1-(4-Chlorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid

To Example 1E (10 mg, 0.037 mniol) and 1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid (13.7 mg, 0.0580 mmol) in DMF (880 mu), was added DIEA (46.0 mu, 0.264 mmol), followed by addition of BOP (25.7 mg, 0.0580 mmol). The reaction mixture was stirred at rt for 4 h then quenched by the addition of a few a drops of water, diluted with methanol, filtered and purified on preparative HPLC to yield Example 1 (11 mg, 44%) as a white powder. MS (ESI) m/z: 486.0, 1H NMR (500 MHz, DMSO-de) delta 8.20 (s, 1H), 7.92 (br s, 1H), 7.75- 7.43 (m, 3H), 7.33- 7.15 (m, 1H), 6.60 – 6.25 (m, 3H), 3.59 (br d, J=6.1 Hz, 2H), 3.19 (br s, 1H), 2.70 (s, 3H), 2.55 (s, 3H), 1.65 (d, J=6.8 Hz, 2H), 1.02 (d, J=6.3 Hz, 3H).

According to the analysis of related databases, 187998-35-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; GLUNZ, Peter W.; LADZIATA, Vladimir; DE LUCCA, Indawati; TORA, George O.; MAISHAL, Tarun Kumar; TANGIRALA, Raghuram; THIYAGARAJAN, Kamalraj; (216 pag.)WO2019/14308; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 139756-02-8, 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 139756-02-8 as follows.

Synthesis of Ba; Step 7. 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide (1 eq) and 3-Bromo-4-methoxybenzaldehyde (1.1 eq) were suspended in ethanol 5 ml and the mixture heated at 70 C for 2 hours after conformation of forming of imine by TLC. Added CuC12 (3 eq) and the reaction mixture heated at 75 C under 02 for 3 hours. After completion of the reaction, the ethanol was removed under vacuum. Then workupwith ethyl acetate and water. Separate the organic layer and Water layer re-extracted with 2×25 ml ethyl acetate. The combined organic layers are washed with brine solution, concentrated under vacuum. The residue was purified by column chromatography on silica the desired product Ba as a white solid; yield 85%. 1H NMR (400 MHz DMSO): 8.31(d J = 2.0Hz 1H),8.29(s 1H),8.14(dd J = 8.8,2.0Hz1H),7.24(dJ= 8.8Hz) 4.14(s 3H),3.93(s 3H)2.8(tJ 7.3Hz 2H),1.76(m 2H),0.95(tJ=7.3Hz 3H). MASS: ESI [M+2 + H] + 377.05; Elemental anal. calcd. for C16H17BrN4O2C, 50.94; H, 4.54; Br, 21.18; N, 14.85; 0, 8.48; found C, 50.89; H, 4.56; Br, 21.21; N,14.83; 0, 8.50.

According to the analysis of related databases, 139756-02-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH; SAWANT, Sanghapal Damodar; GINNEREDDY, Lakshma Reddy; MAHESUNI, Srinivas; SYED, Sajad Hussain; DAR, Mohd Ishaq; NARGOTRA, Amit; MAHAJAN, Priya; VISHWAKARMA, Ram Asrey; WO2015/114647; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 1613191-73-3, name is Allyl 3,5-diamino-1H-pyrazole-4-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 1613191-73-3, Quality Control of Allyl 3,5-diamino-1H-pyrazole-4-carboxylate

To a suspension of allyl 3,5-diamino-lH-pyrazole-4-carboxylate 3 (42.72 g, 234.5 mmol) in DMSO (270.8 mL) / Water (270.8 mL), was added p-TsOH hydrate (46.72 g, 245.6 mmol) and 3-(diisopropylamino)-2-fluoro-prop-2-enal (described in Tetrahedron Letters, 33(3), 357-60; 1992) (38.69 g, 223.3 mmol). The reaction mixture was heated to 100C for 3h during which time a solid slowly precipitated out of solution. The orange suspension was allowed to cool down to RT overnight. The solid was filtered, washed with water and dried under vacuum to give allyl 2-amino-6-fluoro-pyrazolo[l,5-a]pyrimidine-3-carboxylate 4a as a sand solid (45.05 g, 85% yield).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Allyl 3,5-diamino-1H-pyrazole-4-carboxylate, and friends who are interested can also refer to it.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; AHMAD, Nadia; BOYALL, Dean; CHARRIER, Jean-Damien; DAVIS, Chris; DAVIS, Rebecca; DURRANT, Steven; ETXEBARRIA I JARDI, Gorka; FRAYSSE, Damien; JIMENEZ, Juan-Miguel; KAY, David; KNEGTEL, Ronald; MIDDLETON, Donald; ODONNELL, Michael; PANESAR, Maninder; PIERARD, Francoise; PINDER, Joanne; SHAW, David; STORCK, Pierre-Henri; STUDLEY, John; TWIN, Heather; WO2014/89379; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 5744-40-1, 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. 5744-40-1, name is Ethyl 1,3-dimethyl-1H-pyrazole-5-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Dissolve ETHYL-3-METHYLPYRAZOLE-5-CARBOXYLATE (1.0893 g, 7.07 mmol) in 10 mL tetrahydrofuran and add it dropwise to a suspension OF SODIUM HYDRIDE (60%) (377. 6 mg, 9.44 mmol) in 10 mL tetrahydrofuran. After 2 hours, quench the reaction with methyl iodide (excess) and stir for an additional 2 hours. Add water to the reaction and remove the tetrahydrofuran in vacuo. Partition the residue between ethyl acetate and brine. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in VACUO to afford 950. 0 mg of crude 2,5-dimethyl-2H-pyrazole-3-carboxylic acid ethyl ester. Dissolve this material (950.0 mg, 5.65 mmol) in 10 mL tetrahydrofuran and add it dropwise to a slurry of lithium alumininum hydride (220.2 mg) in 20 mL tetrahydrofuran at 0 C. After 30 minutes at this temperature, heat the reaction to reflux for 2 hours. Cool the reaction to room temperature and add 20 mL ethyl acetate to the reaction. Add 5N sodium hydroxide to the reaction until a white precipitate appears. Filter the reaction and concentrate the filtrate in vacuo. Partition the residue between ethyl acetate and water. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to afford 493.7 mg of crude (2, 5-DIMETHYL-2H-PYRAZOL-3-YL)-METHANOL. Dissolve this crude material (493.7 mg, 3.91 mmol) in 20 mL methylene chloride and add MN02 (1.2939 g, 14.88 mmol) to the reaction mixture. Heat the reaction mixture to reflux and allow it to stir for 16 hours. Cool the reaction and filter it through a pad of celite. Concentrate the filtrate in W . CO to afford 444.5 mg of crude product. Purify via Biotage chromatography (25% ethyl acetate/Hexanes) to afford 138.7 mg of the title compound’H NMR (CDCL3) 8 9. 81 (1 H, s), 6.46 (1 H, s), 3.82 (3 H, s), 2.24 (3 H, S).

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

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/9941; (2005); 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. 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine, This compound has unique chemical properties. The synthetic route is as follows., Safety of 1-Methyl-1H-pyrazol-5-amine

(3 S)-7-(2-Chloro-5 -methylpyrimidin-4-yl)-3 -methyl-2-((3 -methylpyrazin-2-yl)methyl)-3 ,4-dihydropyrrolo [1 ,2-a]pyrazin- 1 (2H)-one (125 mg, 0.33 mmol), 1-methyl-i H-pyrazol5-amine (34.9 mg, 0.36 mmol), cesium carbonate (213 mg, 0.65 mmol) and BrettPhos 3rdgeneration pre-catalyst (14.80 mg, 0.02 mmol) were suspended in tert-butanol (5 mL) andde-gassed for 10 minutes. The reaction was heated to 80 °C for 18 hours under nitrogen.The mixture was cooled to room temperature, diluted with EtOAc (50 mL), washed with saturated aqueous sodium bicarbonate (10 mL) and the layers separated. The aqueous portion was washed with ethyl acetate (50 mL) and the combined organics were dried (sodium sulfate) and concentrated in vacuo to a brown gum which was taken up in DMSO(5 mL) and filtered. The crude product was purified by preparative HPLC (Waters XBridge Prep Ci8 OBD column, Sji silica, 30 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1percent NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (3S)-3-methyl-7-(5-methyl-2- ((i-methyl-i H-pyrazol-5 -yl)amino)pyrimidin-4-yl)-2-((3 -methylpyrazin-2-yl)methyl)-3 ,4-dihydropyrrolo[i,2-a]pyrazin-i(2H)-one (97 mg, 67.0 percent) as a white solid. ?H NMR(500 MHz, DMSO, 30 °C) 1.43 (3H, d), 2.58 – 2.6 (3H, m), 2.83 (3H, s), 3.94 (3H, s), 4.15- 4.25 (iH, m), 4.44 (iH, dd), 4.55 – 4.67 (2H, m), 5.60 (iH, d), 6.52 (iH, d), 7.50 (iH, d),7.59 (iH, d), 7.90 (iH, d), 8.49 (iH, d), 8.64 – 8.71 (2H, m), 9.33 (iH, s). mlz: ES+[M+H]+ 443.

According to the analysis of related databases, 1192-21-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; WARD, Richard, Andrew; GRAHAM, Mark, Andrew; SWALLOW, Steven; JONES, Clifford, David; (282 pag.)WO2016/162325; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 27006-76-4, 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. 27006-76-4 name is 5-Chloro-1,3-dimethyl-1H-pyrazole-4-carboxaldehyde, 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.

General procedure: To a solution of acetonitrile (20 mL), compound 3 (0.02 mol), benzyltriethylamine chloride (0.001 mol), KOH (0.024 mol), and appropriate phenols were added and refluxed for 5-48 h. The solvent was removed to give a residue under reduced pressure, which was dissolved with CH2Cl2 and washed using 10% KOH solution. Anhydrous MgSO4 was used to dry the dichloromethane layer. Compounds 4a-4l and 5a-5l were obtained after evaporation of the solvents, which were used to prepare compounds 6a-6l and 7a-7l without purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Chloro-1,3-dimethyl-1H-pyrazole-4-carboxaldehyde, and friends who are interested can also refer to it.

Reference:
Article; Song, Ming-Xia; Wu, Yi; Deng, Xian-Qing; Letters in drug design and discovery; vol. 13; 8; (2016); p. 800 – 808;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 3469-69-0, 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. 3469-69-0, name is 4-Iodopyrazole, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: Step 1: 1-methyl-4-iodopyrazole 1H-4-iodopyrazole (20 g), potassium carbonate (28.45 g) and acetone (120 mL) were added into a round bottomed flask (250 mL) and agitated for 10 min. Then iodomethane (17.56 g) was added and the mixture was agitated at room temperature over night. After that, the mixture was filtrated and concentrated, the residue was recrystallized from n-hexane to prodce 1-methyl-1H-4-iodopyrazole (15 g) as white acicular crystal. 1H-NMR (300Hz, CDCl3) delta: 7.48 (s, 1H), 7.40 (s, 1H), 3.92 (s, 3H).

The chemical industry reduces the impact on the environment during synthesis 4-Iodopyrazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Shanghai Institute Materia Medica, Chinese Academy Of Sciences; DUAN, Wenhu; GENG, Meiyu; CHEN, Fang; AI, Jing; CHEN, Yi; ZHAN, Zhengsheng; LV, Yongcong; WANG, Ying; DING, Jian; EP2650293; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics