Tag: M.W:100-200

Electric Literature of 151049-87-5, 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 151049-87-5 as follows.

dihydroquinolin- I (211)-yl)-N-methyl- I -(tetrahydro-2H-pyran-4-yI)-6,7-dihydro- I Hpyrazolo[4,3-c}pyridine-5(4H)-carboxamide (Intermediate S. 100 mg, 0.2 mmol) in THF (2.5 mL) and water (0.5 mL) was added chloro(2-dicyclohexylphosphino-2?,4,6?-tri-i-propy1-i,1?-biphenyl)(2?-amino-1,1?-biphenyl-2-yl) palladium (II) (16 mg, 0.02 mmol), 2- (dicyclohexylphosphino)-2?,4?,6?-triisopropylbiphenyl (9 mg, 0.02 mmol), 3 -bromo- 1-methyl- pyrazole (48 mg, 0.3 mmol) and Na2CO3 (42 mg, 0.4 mmol). The reaction was heated to 60C for 16 h under a nitrogen atmosphere. After cooling the reaction to room temperature, the mixture was concentrated in vacuo. DCM (50 mL) was added and the mixture was washedwith water (30 mL x 3) and brine (30 mL). The organic layer was dried over anhydrousNa2SO4, filtered and concentrated in vacuo. The crude residue was purified by reverse phasechromatography (acetonitrile 40-70% / 0.05% NH4OH in water) to give the title compound(11 mg, 11%) as a white solid. 111 NMR (400 MHz, DM80-cl6) 6 7.73 (d, Jr 2.0 Hz, IH),7.44 (t,J 55.6 Hz, IH), 7.32 (s, lH), 6.86 (s, 111), 6.55 (d,Jr 4.0 Hz, IH), 6.46 (s, 1H),4.33 -4.23 (m, IH), 4.02 (s, 211), 3.95 – 3.93 (m, 211), 3.86 (s, 311), 3.61 – 3.58 (m, 414), 3.48-3.42 (m, 211), 2.89-2.71 (m, 4H), 2.53 (d,J= 4,4 Hz, 3H), 2.01 – 1.93 (m, 4H), 1.82- 1.80 (m, 211). LCMS M/Z (M+H) 526.

According to the analysis of related databases, 151049-87-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; ROMERO, F. Anthony; MAGNUSON, Steven; PASTOR, Richard; TSUI, Vickie Hsiao-Wei; MURRAY, Jeremy; CRAWFORD, Terry; ALBRECHT, Brian, K.; COTE, Alexandre; TAYLOR, Alexander, M.; LAI, Kwong Wah; CHEN, Kevin, X.; BRONNER, Sarah; ADLER, Marc; EGEN, Jackson; LIAO, Jiangpeng; WANG, Fei; CYR, Patrick; ZHU, Bing-Yan; KAUDER, Steven; (0 pag.)WO2016/86200; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 2458-26-6, 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. 2458-26-6, name is 3-Phenyl-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows.

Step 3: 1-Delta4′-[3-Methyl-4-(3-phenyl-pyrazol-1-ylmethyl)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid 1-[4′-(4-Bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester (0.132 g, 0.3 mmol) and 3-phenyl-1H-pyrazole (0.043 g, 0.3 mmol) were combined in DMF. Sodium hydride (60% in mineral oil; 0.014 g, 0.35 mmol) was added, and the reaction was stirred at room temperature for 1.5 hours. Once no starting material was seen by analytical LCMS, the mixture was diluted with EtOAc and 1N aqueous HCl. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with H2O and brine, and then dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC to give the title compound.

The chemical industry reduces the impact on the environment during synthesis 3-Phenyl-1H-pyrazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AMIRA PHARMACEUTICALS, INC.; US2011/82164; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 3524-32-1, name is 5-Amino-1,3-dimethylpyrazole, 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. Product Details of 3524-32-1

Step 1 An oven dried 100 mL round bottomed flask equipped with a stirring bar was cooled under nitrogen and charged with 1,3-dimethyl-1H pyrazol-5-amine (491.7 mg, 4.42 mmol) and 45 mL of anhydrous THF (0.1M). The THF solution was treated with solid LiHMDS (1.481 g, 8.84 mmol) and stirred at RT for 5 min after which yellow solids formed. C-2 (500 mg, 2.21 mmol) was added in one portion. The flask was equipped with a reflux condenser, and the reaction mixture heated to 80 C. The reaction was monitored by LCMS and was 90% complete after 2 h at 80 C. The reaction mixture was cooled to RT, and the THF removed on a rotary evaporator. The crude residue was partitioned between DCM and water. The DCM layer was washed with brine, dried (MgSO4) filtered and concentrated. The crude residue was absorbed onto Celite and purified by SiO2 chromatography eluting with an EtOAc/heptane gradient (50 to 100% EtOAc) to afford 328 mg (47%) of 6-bromo-N-(1,3dimethyl-1H pyrazol-5-yl)-isoquinolin-3-amine (82).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3524-32-1, its application will become more common.

Reference:
Patent; Genentech, Inc.; Array BioPharma Inc.; Blake, Jim; Chen, Huifen; Chicarelli, Mark; Gaudino, John; Gazzard, Lewis; Kintz, Sam; Mohr, Pete; Robarge, Kirk; Schwarz, Jacob; Zhou, Aihe; US2014/66453; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 139756-02-8, name is 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide, 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. HPLC of Formula: C8H14N4O

General procedure: We intended to synthesize compounds based on 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one scaffold by using microwave assisted protocol (Scheme 1). In this direction we started the studies for optimization of synthesis of 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 3a. The optimization studies were initiated by screening of different oxidizing agents as depicted in Table1, see Supplementary data using DMSO:Water in 1:1 proportion to see the conversion in desired product. Amongst all oxidants, the best result was observed with K2S2O8, in equivalence studies for catalyst, 3eq. of catalyst has given maximum yields (Table1, see Supplementary data). Therefore, all reactions were conducted using this condition after optimization of catalyst. However, oxone has also given the product 3a with minor yields. After screening of the catalyst we started study of selectivity for solvent that could affect the formation of 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 3a. The solvent screening was carried out to find out the best conversion, the mixture of DMSO:H2O in 1:1 proportion has given the best results with excellent yields (Table2, see Supplementary data). The microwave protocols were optimized for this reaction as mentioned in Table 3, see Supplementary data; the reactions carried under different microwave Watt powers have given varied results. Wherein, entry 3(b) (Table3, see Supplementary data) was found to be the best condition for maximum conversion. A series of compounds based on 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one scaffold was synthesized using these optimized conditions, wherein, all kind of substrates with diversity around aryl ring were chosen for conversion and in all cases products obtained in good to excellent yields (Table1).

The synthetic route of 4-Amino-1-methyl-3-N-propyl-1H-pyrazole-5-carboxamide has been constantly updated, and we look forward to future research findings.

Reference:
Article; Reddy, G. Lakshma; Guru, Santosh Kumar; Srinivas; Pathania, Anup Singh; Mahajan, Priya; Nargotra, Amit; Bhushan, Shashi; Vishwakarma, Ram A.; Sawant, Sanghapal D.; European Journal of Medicinal Chemistry; vol. 80; (2014); p. 201 – 208;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 14521-80-3,Some common heterocyclic compound, 14521-80-3, name is 3-Bromo-1H-pyrazole, molecular formula is C3H3BrN2, 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: Pyrazoles 4 (0.5 mmol), sodium sulfinate 2 (1.0 mmol) and NBS or NIS (1.5 mmol) were dissolved in 2 mL of EtOAc solvent. the reaction mixture was stirred at room temperature under air for 12 h. After the reaction, the resulting mixture was extracted with EtOAc. The combined organic phase was dried over anhydrous Na2SO4 and the solvent was then removed under vacuum. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate, 3:1) to afford the corresponding product.

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-1H-pyrazole, its application will become more common.

Reference:
Article; Fu, Lili; Bao, Xiaodong; Li, Shanshan; Wang, Lingtian; Liu, Zhiguo; Chen, Wanzhi; Xia, Qinqin; Liang, Guang; Tetrahedron; vol. 73; 17; (2017); p. 2504 – 2511;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 27006-76-4, name is 5-Chloro-1,3-dimethyl-1H-pyrazole-4-carboxaldehyde, 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 27006-76-4, COA of Formula: C6H7ClN2O

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

Reference of 63874-95-3, 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. 63874-95-3 name is 1-Benzyl-1H-pyrazole-4-carbaldehyde, 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 Example 13 (53 mg, 0.17 mmol, 1.0 eq) and 1-methyl-1H-imidazole-2-carbaldehyde (28 mg, 0.25 mmol, 1.5 eq) in THF (2 mL) under a N2 atmosphere was added NaBH(OAc)3 (72 mg, 0.34 mmol, 2.0 eq) and the mixture was stirred at RT overnight. The mixture was purified by C18 reverse phase column (Biotage, 30% to 70% ACN in water, 0.1% TFA) to afford the title compound (22 mg, 34%) as a white solid. LCMS: [M+H]+ 384.2. 1H NMR (400 MHz, CDCl3) delta 8.10 (d, J=8.4 Hz, 1H), 7.65 (d, J=7.2 Hz, 1H), 7.41 (s, 2H), 7.20 (s, 1H), 4.78 (s, 2H), 3.98 (s, 3H), 3.80 (s, 2H), 3.40 (m, 2H), 3.17-3.00 (m, 3H), 2.59 (s, 3H), 2.24 (m, 2H), 1.95 (m, 2H).

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

Reference:
Patent; Ribon Therapeutics Inc.; Schenkel, Laurie B.; Vasbinder, Melissa Marie; Kuntz, Kevin Wayne; Swinger, Kerren Kalai; (179 pag.)US2019/194174; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 852227-86-2, 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. 852227-86-2 name is 5-(Chloromethyl)-1,3-dimethyl-1H-pyrazole, 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.

A solution of compound 9 (56 mg, 0.12 mmol, 1.0 equiv) in anhydrous DMF (0.2 mL) was treated with 60% sodium hydride (6.0 mg, 0.15 mmol, 1.2 equiv) at room temperature. After stirring at this temperature for 5 min, 5-(chloromethyl)-l,3-dimethyl- lH-pyrazole (21 mg, 0.14 mmol, 1.1 equiv) was introduced. Then the mixture was stirred at room temperature for 1 hour. The reaction was quenched with saturated aqueous NaHCO3 solution. The resultant solution was extracted with ethyl acetate. The combined organic extracts were washed once with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed on prep-TLC (ethyl acetate/dichloromethane/methanol 20:20:1, 2 runs) to afford compound 11 (27 mg, 39 %) as an oil. MS 561 (MH)+, 619 (MOAc)”, 597 (MCl37)”, 595 (MCl35)”and 559 (M-H)”. Purity >98% (HPLC).

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

Reference:
Patent; SEQUOIA PHARMACEUTICALS, INC.; WO2009/105776; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 2075-45-8, 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. 2075-45-8, name is 4-Bromo-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 4-bromopyrazole (4.00 g, 27.2 mmol) in anhydrous THF(25 mL) cooled to 0 C was added NaH (60% dispersion in mineral oil, 1.63 g, 40.8 mmol) in four equivalent portions. The contents were stirred at 0 C for 30 minutes, and then 2- (trimethylsilyl)ethoxymethyl chloride (5.06 mL, 28.6 mmol) was added slowly. The reaction was stirred at room temperature for 16 hours, diluted with diethyl ether (200 mL), and washed with brine (100 mL). The organic phase was dried over anhydrous Na^SCL and concentrated under reduced pressure to afford 22 as a clear oil (7.50 g, 99% yield).1H NMR (400 MHz, CDCI3) delta 7.59 (s, 1H), 7.49 (s, 1H), 5.38 (s, 2H), 3.55 (t, J= 8.1 Hz, 2H), 0.90 (t, J= 8.5 Hz, 2H), -0.02 (s, 9H).13C NMR (101 MHz, CDCI3) delta 140.5, 129.6, 94.8, 80.8, 67.1, 17.9, -1.3.

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

Reference:
Patent; YALE UNIVERSITY; JORGENSEN, William L.; TRIVEDI-PARMAR, Vinay; (142 pag.)WO2019/178480; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 3524-32-1, 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. 3524-32-1, name is 5-Amino-1,3-dimethylpyrazole, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: A mixture of 5-amino-3-methylpyrazole (1 mmol), isatin or acenaphthylene-1,2-dione (1 mmol), thioacid (1 mmol), and p-TSA (30 mol %) in CH3CN (5 mL) was stirred at 80 C for 12-24 h. After completion of the reaction confirmed by TLC (eluent acetone/petroleum ether, 1:2), the reaction mixture was cooled to room temperature. Then, the solvent was removed under vacuum. The solid was recrystallizated from CH3CN and ethanol to afford the pure 4 or 6 as a white or yellow powder.

The chemical industry reduces the impact on the environment during synthesis 5-Amino-1,3-dimethylpyrazole. I believe this compound will play a more active role in future production and life.

Reference:
Article; Chen, Hui; Shi, Daqing; Tetrahedron; vol. 67; 31; (2011); p. 5686 – 5692;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics