Day: July 16, 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. 632365-54-9, name is Methyl 5-amino-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C5H7N3O2

To an ice cold suspension of 0.92 g (23 mmol) of sodium hydride (NaH 60% dispersion in mineral oil) (previously washed with hexane and dried under vacuum) in 25 mL of 1,2- dimethoxyethane (DME) was added 0.9 g (5.76 mmol) of [METHYL CYCLOHEXYLACETATE,] and the resulting mixture was stirred at [0 C] for 20 min. Then 1.2 g (8.56 mmol) [OF ETHYL 2-FUROATE] was added, and the reaction mixture was heated at reflux overnight. The mixture was then cooled to [0C,] quenched by the addition of 1 M [HC1] solution to pH=3, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give a brown oil which was chromatographed on silica gel [(BIOTAGE ;] 10% hexane in dichloromethane) to afford 1.1 g (76% yield) of desired 2-cyclohexyl-3-furan-2-yl-3- [OXO-PROPIONIC ACID METHYL ESTER] as indicated by 1H NMR. A mixture of 1.1 g (4.4 mmol) [OF 2-CYCLOHEXYL-3-FURAN-2-YL-3-OXO-P7 OPIONIC ACID] [METHYL ESTER,] 0.592 g (4.2 mmol) of 5-amino-1H-pyrazole-3-carboxylic acid methyl ester, 76 mg (0.4 mmol, 10 mol%) of p-toluenesulfonic acid monohydrate (PTSA), and 50 mL of chlorobenzene was heated at 120 [C] overnight. The reaction mixture was then concentrated to a residue which was chromatographed on silica gel (7% methanol in dichloromethane) to afford 0.46 g (32% yield) of desired 6-cyclohexyl-5-furan-2-yl-7-oxo-4,7-dihydro- pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester as indicated [BY IH] NMR; LC-MS- calcd for [C18HL9N304] [[M++H] +] : 342.14, found: 342.3. Conversion of 6-cyclohexyl-5-furan-2-yl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine- 2-carboxylic acid methyl ester to 6-cyclohexyl-5-furan-2-yl-7-oxo-4,7-dihydro-pyrazolo[1,5- [AJPYYIMIDINE-2-CARBOXYLIC ACID] (595) was accomplished via the well known LiOH saponification protocol where the yield was 77%. [LC-MS-CALCD] for [CI7HI7N304] [M++H]+: 328.13, found : 328. 1. 1H NMR [(DMSO-D6)] [8] 8.06-8. 05 (d, J= 2 Hz, 1H), 6.99-6. 98 (d, J= 3.6 Hz, 1H), 6.80-6. 78 (d [OF D,] J= 3.6 Hz, J= 2 Hz, [1H),] 6.39 (s, [1H),] 2.79-2. 71 [(M,] 1H), 2.25-2. 16 [(M,] 2H), 1.77-1. 75 [(M,] [2H),] 1.66-1. 65 [(M,] 1H), 1.59-1. 55 [(M,] 2H), 1.25-1. 20 [(M,] 3H). Note that the same synthetic scheme was carried out for [3-FLUORO-BENZOIC ACID METHYL] ester as depicted above to afford [6-CYCLOHEXYL-5-(3-FLUORO-PHENYL)-7-OXO-4, 7-DISLYDRO-] pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (598); the cyclization yield was slightly improved (54%).

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; NEOGENESIS PHARMACEUTICALS, INC.; WO2003/101993; (2003); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 1072-68-0, name is 1,4-Dimethylpyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. COA of Formula: C5H8N2

1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole A solution of 1,4-dimethyl-1H-pyrazole (480.0 mg, 4.993 mol) in tetrahydrofuran (20 mL, 300 mmol) at 0 C. was added 1.6 M n-butyllithium in hexane (4.7 mL, 7.5 mmol). The solution was stirred at room temperature for 1 h and then cooled to -78 C. To the solution was added 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.63 mL, 7.99 mmol). The reaction mixture was stirred at -78 C. for 0.5 h, then warmed up to 0 C. (taking 0.5 h). The reaction was quenched with brine and extracted with EtOAc (3*). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by combi-flash chromatography and eluted with EtOAc/hexane (0-60%). The purification gave 142 mg of product as white solid.

The synthetic route of 1072-68-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Incyte Corporation; Huang, Taisheng; Feng, Hao; Kong, Lingquan; Wang, Anlai; Ye, Hai Fen; US2013/96144; (2013); 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. 400877-57-8, name is Methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C6H7N3O4

B) Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate To a solution of methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate (10 g) in methanol (200 mL), palladium-carbon (10%) (2 g) was added, and the mixture was stirred at room temperature for 6 hours in a hydrogen atmosphere (45 psi). Palladium-carbon was filtered off, and then, the filtrate was concentrated to obtain the title compound (8.57 g). 1H NMR (400 MHz, CDCl3) delta 3.86 (3H, s), 3.92 (3H, s), 4.08 (2H, brs), 6.96 (1H, s).

The synthetic route of 400877-57-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; ASANO, Yasutomi; KOJIMA, Takuto; KURASAWA, Osamu; WONG, Tzu-Tshin; HIRATA, Yasuhiro; IWAMURA, Naoki; SAITO, Bunnai; TANAKA, Yuta; ARAI Ryosuke; IMAMURA, Shinichi; YONEMORI, Kazuko; MIYAMOTO, Yasufumi; KITAMURA, Shuji; SANO, Osamu; (222 pag.)EP3287441; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. Quality Control of 1,3-Dimethyl-1H-pyrazol-4-amine

Example 4.28 7- [ [2- [(1 ,3-Dimethylpyrazol-4-yl)aminol -5-fluor o-4-pyridvH aminol -4-(4- isopropylpiperazin-l-yl)-2-methyl-isoindolin-l-one A mixture of 7-[(2-chloro-5-fluoropyridin-4-yl)amino]-2-methyl-4-(4-propan-2- ylpiperazin-l-yl)-3H-isoindol-l-one (150 mg, 0.36 mmol), l,3-dimethylpyrazol-4-amine (80 mg, 0.72 mmol), cesium carbonate (234 mg, 0.72 mmol), 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (24.92 mg, 0.04 mmol) and palladium(II) acetate (6.45 mg, 0.03 mmol) was suspended in DMA (2 mL) under an atmosphere of nitrogen. The mixture was heated at 1500C for 60 minutes in a microwave reactor and then allowed to cool to room temperature. The mixture was filtered and the filtrate evaporated. The residue was dissolved in MeOH (20 mL) and the solution made acidic (pH6) by the addition of 2M HCl. The mixture was loaded onto an SCX column and the product eluted first wit MeOH and then with a 0.7M solution OfNH3 in MeOH. Fractions containing product were combined and evaporated and the residue was then purified by preparative HPLC. Fractions containing product were combined and evaporated to afford example 4.28 (45.4 mg, 26% yield); 1H NMR spectrum (300 MHz, DMSO): delta 1.02 (6H, d), 2.11 (3H, s), 2.60 (4H, t), 2.70 (IH, m), 2.99 (4H,m), 3.06 (3H, s), 3.70 (3H, s), 4.48 (2H, s), 6.92 (IH, d), 7.15 (IH, d), 7.39 (IH, d), 7.86 – 7.93 (3H, m), 9.26 (IH, d); Mass spectrum: m/z (ESI+) (M+H)+ = 493.44.

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; WO2009/153589; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 916766-83-1, name is 3-(4-(Chloromethyl)phenyl)-1-methyl-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. category: pyrazoles-derivatives

Triethyl 2-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)ethane-1,1,1-tricarboxylate 1m Prepared from 3-[4-(chloromethyl)phenyl]-1-methyl-1H-pyrazole (Maybridge, CC23824) according to the general alkylation protocol, to give the title compound in the form of a yellow oil (yield?95%). 1H NMR (CDCl3): delta 1.20 (t, 9H, J=7.25 Hz); 3.51 (s, 2H); 3.93 (s, 31-1); 4.19 (q, 6H, J=7.25 Hz); 6.49 (d, 1H, J=2.25 Hz); 7.28 (d, 2H, J=8 Hz); 7.65 (d, 2H, J=8 Hz); 7.99 (s, 1H).

The synthetic route of 916766-83-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Commissariat A l’Energie Atomique et Aux Energies Alternatives; Devel, Laurent; Beau, Fabrice; Czarny, Bertrand; Dive, Vincent; US8691753; (2014); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 31108-57-3,Some common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, molecular formula is C4H3N3, 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.

In a microwave tube propan-2-yl (2R)-oxirane-2-carboxylate (2.00 g, 15.4 mmol) and 4- cyanopyrazole (3.58 g, 38.4 mmol) were dissolved in isopropanol (10 ml). The RM was heated in a microwave reactor at 100C for 3 h. The RM was concentrated in vacuo, then purified by prep-HPLC: (column: Agela Innoval ODS-2 100mm*350mm; mobile phase: [water (0.1 % TFA) – ACN]; B %: 5 % – 25 %, 20 min) to obtain the title compound as a yellow oil. MS ES+: 224.2. NMR (400MHz, chloroform-) delta 7.94 (s, 1H), 7.78 (s, 1H), 5.13 – 5.06 (m, 1H), 4.51 – 4.48 (m, 2H), 3.72 (s, 1H), 1.32 – 1.26 (m, 6H).

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NODTHERA LIMITED; BOCK, Mark G.; WATT, Alan Paul; PORTER, Roderick Alan; HARRISON, David; (229 pag.)WO2019/25467; (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. 15754-60-6, name is 1-(tert-Butyl)-1H-pyrazole, A new synthetic method of this compound is introduced below., Application In Synthesis of 1-(tert-Butyl)-1H-pyrazole

0481-1 Iodine (1.59 g) and ammonium cerium nitrate (3.45 g) were added to a solution of 1-(tert-butyl)-1H-pyrazole (1.30 g) in acetonitrile (6 mL), followed by stirring at room temperature for 2 hours. After ethyl acetate and water were added to the reaction mixture, the organic layer was collected by separation, washed sequentially with a 10% sodium hydrogen sulfite aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure, thereby obtaining 1-(tert-butyl)-4-iodo-1H-pyrazole (487 mg). MS m/z (M+H): 251.

The synthetic route of 15754-60-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FUJIFILM Corporation; FURUYAMA, Hidetomo; KURIHARA, Hideki; TERAO, Takahiro; NAKAGAWA, Daisuke; TANABE, Shintaro; KATO, Takayuki; YAMAMOTO, Masahiko; SEKINE, Shinichiro; MASHIKO, Tomoyuki; INUKI, Shinsuke; UEDA, Satoshi; US2015/322063; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 6076-14-8, name is Ethyl 4-bromo-5-methyl-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 6076-14-8, Formula: C7H9BrN2O2

Reference Example 24; Ethyl 4-bromo-1-[4-(tert-butoxycarbonyl)benzyl]-5-methyl-1H-pyrazole-3-carboxylate Ethyl 4-bromo-5-methyl-1H-pyrazole-3-carboxylate (25.5 g) was dissolved in DMF (500 mL), ice-cooled, and potassium tert-butoxide (14.7 g) was added. The reaction mixture was stirred for 10 min, and a solution (14.7 g/50 mL) of tert-butyl 4-(bromomethyl)benzoate in DMF was added dropwise slowly. The reaction mixture was stirred at 0 C. for 1.5 hr, poured into saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was purified by column chromatography (hexane-ethyl acetate) to give two kinds of positional isomers. A high polar compound was washed with diisopropyl ether-hexane to give the title compound (11.6 g) as colorless crystals.1H-NMR (CDCl3) delta: 1.43 (3H, t), 1.58 (9H, s), 2.16 (3H, s), 4.45 (2H, q), 5.45 (2H, s), 7.13 (2H, d), 7.95 (2H, d).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; US2009/270359; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 31108-57-3,Some common heterocyclic compound, 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, molecular formula is C4H3N3, 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 7(2R)-4-(4-cvano-1 H-pyrazol-1 -yl)-N-hvdroxy-2-methyl-2-Step A: (2R)-4-(4-cvano-1 H-pyrazol-1 -yl)-2-methyl-2-(methylsulfonyl)butanoic acid To a solution of 4-cyanopyrazole (0.150 g, 1 .61 mmol, 1 eq) in acetonitrile (10 mL) was added cesium carbonate (1 .31 g, 4.03 mmol, 2.5 eq), sodium iodide (0.048 mg, 0.322 mmol, 0.2 eq) and (R)-ethyl 4-bromo-2-methyl-2- (methylsulfonyl)butanoate (0.555 g, 1 .93 mmol, 1 .2 eq). The mixture was heated at 50 C overnight. The reaction mixture was cooled to room temperature and was filtered via Buchner funnel, and eluted with EtOAc. The filtrate was concentrated under reduced pressure and was diluted with up in tetrahydrofuran (5 mL) and water (5 mL). Lithium hydroxide (0.1 16 g, 4.83 mmol, 3 eq) was added, and the reaction mixture was allowed to stir at room temperature for four hours. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate (10mL), and concentrated again. This yielded (2R)-4-(4-cyano-1 H-pyrazol-1 -yl)-2-methyl-2- (methylsulfonyl)butanoic acid as a yellow oil, which was carried on crude in the next step. LC-MS M+H+ 272.2.

The synthetic route of 31108-57-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; BROWN, Matthew F.; CHEN, Jinshan Michael; MELNICK, Michael; MONTGOMERY, Justin I.; REILLY, Usa; WO2012/137099; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 138786-86-4, These common heterocyclic compound, 138786-86-4, name is Methyl 4-nitro-1H-pyrazole-3-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.

PART I: Synthesis Scheme I, shows that 4-nitro-1H-pyrazole-3-carboxylic acid (compound 12) was alkylated with methyl iodide in the presence of potassium carbonate in DMF. After flash chromatography on silica gel, two regioisomers, alkyl 1-alkyl-4-nitro-1H-pyrazole-3-carboxylate (compound 13a, 1,3-isomer) and alkyl 1-alkyl-4-nitro-1H-pyrazole-5-carboxylate (compound 13b, 1,5-isomer) were obtained in 26% and 74% yield, respectively. The structures of the isomers (compounds 13a, 13b) were determined by NOESY analysis: a NOESY correlation was observed between H-5 and alkyl protons in compound 13a.16 The nitro group of compounds 13a and 13b was reduced by hydrogenation in the presence of a catalytic amount of catalytic amount of 10% Pd/C to produce amines compounds 14a and 14b, respectively. Cyclization of compound 14b with urea afforded compound 15. Chlorination of compound 15 with POCl3 and DIPEA in toluene afforded compound 16 in 68% yield. Treatment with appropriate substituted anilines in isopropanol with 1 drop of conc. HCl with compound 16, provided the instant compounds 4-11 of this invention (65-78% yields).

The synthetic route of 138786-86-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Duquesne University of the Holy Spirit; Gangjee, Aleem; (26 pag.)US2019/276457; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics