Month: September 2021

These common heterocyclic compound, 285984-25-0, name is 3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-amine, 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. COA of Formula: C14H19N3

Intermediate B: Phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate A solution of 3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-amine (Intermediate A) (20 g, 87.0 mmol) in isopropyl acetate (240 mL) was added to a stirred solution of sodium carbonate (11.3 g, 106 mmol) in water (80 mL). After 10 min phenyl chloroformate (12.1 mL, 96 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with water (160 mL), the layers were separated and the organics were washed with water (2*80 mL), brine (80 mL), dried (MgSO4) and concentrated in vacuo. The resulting yellow solid was suspended in 10% ether/iso-hexane (320 mL) and stirred until a uniform suspension was obtained. The solid was collected by filtration and washed with iso-hexane to yield the subtitle compound phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate as a white powder (27.3 g, 88%); Rt 2.65 min (Method 1); m/z 350 (M+H)+ (ES+); 1H NMR delta:1.29 (9H, s), 2.37 (3H, s), 6.35 (1H, s), 7.10-7.23 (3H, overlapping m), 7.33-7.46 (6H, overlapping m), 9.99 (1H, s).

The synthetic route of 3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RESPIVERT LTD; TOPIVERT PHARMA LTD.; LONGSHAW, ALISTAIR IAN; FORDYCE, EUAN ALEXANDER FRASER; ONIONS, STUART THOMAS; KING-UNDERWOOD, JOHN; VENABLE, JENNIFER; US2015/232450; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 288-13-1, name is 1H-Pyrazole, 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 288-13-1, Product Details of 288-13-1

To a solution of 1H-pyrazole (5.00 g) in toluene (67.0 mL) were added dimethylsulfamoyl chloride (7.89 mL) and triethylamine (13.3 mL) at room temperature, and the reaction mixture was stirred at room temperature for 18 hr. The resulting solid was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (6.24 g). 1H NMR (400 MHz, CDCl3) delta 2.91 (6H, s), 6.38 (1H, dd, J = 2.6, 1.8 Hz), 7.72 (1H, d, J = 1.2 Hz), 7.96 (1H, d, J = 2.4 Hz)

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, 1H-Pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Takeda Pharmaceutical Company Limited; NAGAMIYA, Hiroyuki; YOSHIDA, Masato; SETO, Masaki; MARUI, Shogo; ODA, Tsuneo; ISHICHI, Yuji; SUZUKI, Hideo; KUSUMOTO, Tomokazu; YOGO, Takatoshi; RHIM, Chul Yun; YOON, Cheolhwan; LEE, Gil Nam; KANG, Hyun Bin; KIM, Kwang Ok; JEON, Hye Sun; EP2818473; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 57999-06-1,Some common heterocyclic compound, 57999-06-1, name is 4-Phenyl-1H-pyrazol-5-amine, molecular formula is C9H9N3, 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.

[00237] Sodium metal (0.64g, 28mmol) was washed with petrol, and then cut into small pieces. The pieces were added to dry toluene (5ml). More dry toluene (5ml) and EtOAc (3.7ml, 38mmol) were added, followed by ethyl formate (0.64ml, 8mmol) dropwise. The mixture was heated at 5O0C for 20 minutes, then cooled to room temperature and stirred for 30 minutes. Additional ethyl formate (ImI, 12.5mmol) was added dropwise, and the mixture stirred at room temperature for 1 hour. A final batch of ethyl formate (ImI, 12.5mmol) was added dropwise, and the mixture stirred at room temperature overnight. The mixture was then diluted with dry EtOH (200ml), and 4-phenyl-lH-pyrazol-5 -amine (2g, 12.6mmol) was added. The mixture was heated under reflux overnight. The mixture was cooled and concentrated. The solid residue was dissolved in hot water and filtered. The filtrate was acidified with cone. HCl until pHl. The precipitate was then filtered off, washed with ether, and dried in vacuo to yield 1.4g (52.7%) of the title compound. 1H NMR (d6-DMSO): 12.30 (IH, d, J 4.3), 8.23 (IH, s), 7.82 (IH, t, J 7.0), 7.60 (2H, d, J 7.1), 7.46 (2H, d, J 7.9), 7.30 (lH, t, J7.4), 5.79 (IH, d, J7.3).

The synthetic route of 57999-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BioMarin IGA, Ltd.; WREN, Stephen Paul; WYNNE, Graham Michael; LECCI, Cristina; WILSON, Francis Xavier; WO2010/86040; (2010); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 16617-46-2, 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. 16617-46-2, name is 3-Amino-1H-pyrazole-4-carbonitrile belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Following the procedure described in Example 11 wherein dioxane was used as the solvent instead of tetrahydrofuran and hexane was added instead of water after the reaction was completed, 86percent of the product was obtained with m. p. 183-187 °C Example 13 Following the procedure described in Example 1 wherein hydrobromic acid was used as the catalyst instead of hydrochloric acid, 81percent of the product was obtained with m. p. 184- 188 °C.

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

Reference:
Patent; ZENTIVA, A.S.; WO2004/37824; (2004); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 637336-53-9,Some common heterocyclic compound, 637336-53-9, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, molecular formula is C6H9N3O2, 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.

Synthesis of Compound 32.6 [0287] To a solution of 32.5 (250 mg, 0.5 mmol, 1.0 eq) in DMF (5 mL) were added methyl 4-amino-l-methyl-lH-pyrazole-3-carboxylate (155 mg, 1.0 mmol, 2.0 eq), HBTU (190 mg, 0.5 mmol, 1.0 eq) and DIPEA (130 mg, 1.1 mmol, 2.0 eq). The reaction was stirred at room temperature for 2 h, diluted with EA (100 mL). The mixture was washed with water (30 mL x 3), brine (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by prep-TLC (PE : EA = 1 : 1) to give 32.6 (100 mg, yield: 31%) as a red oil. 1H NMR (400 MHz, DMSO- 6) D delta: 10.29 (s, 1H), 9.07 (s, 1H), 8.61 (d, J = 5.2 Hz, 1H), 8.43 (s, 1H), 8.32 (s, 1H), 7.65 (d, J = 4.8 Hz, 1H), 6.73 (t, J = 5.6 Hz, 1H), 3.96 (s, 3H), 3.93-3.89 (m, 5H), 2.87 (q, J = 6.4 Hz, 2H), 1.60-1.57 (m, 2H), 1.52 (s, 9H), 1.38 (s, 9H), 1.26-1.23 (m, 6H); ESI-MS (M+H) +: 642.0.

The synthetic route of 637336-53-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOGEN IDEC MA INC.; JENKINS, Tracy; VESSELS, Jeffery; WO2014/143672; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference 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.

Synthesis of III-B17 To a solution of III-B16 (90 mg, 0.2 mmol) and lH-pyrazole-4-carbonitrile (37.9 mg, 0.4 mmol) in acetone (5 mL) was added K2C03 (56.2 mg, 0.4 mmol). After stirring at 25C for 2 h, the reaction mixture was extracted with EtOAc (3 x 30 mL). The combined organic solution was washed with saturated brine (30 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by flash column (0-30% of EtOAc in PE) and then by (1240) Prep-HPLC (Column: Waters Xbridge Prep OBD C18 150*30 5 pm; Condition: water (10 mM NH4HC03)-ACN; Begin B: 70; End B: 90; Gradient Time(min): 7; 100%B Hold (1241) Time(min): 1) to give III-B17 (32.6 mg, 53%) as a solid. 1H NMR (400 MHz, CDCl3) dH 7.86 (s, 1H), 7.81 (s, 1H), 5.04 (dd, J= 18.0, 95.6 Hz, 2H), 3.45-3.33 (m, 5H), 2.50 (t, J= 8.8 Hz, 1H), 2.40-2.23 (m, 2H), 1.88-1.10 (m, 23H), 1.00-0.83 (m, 1H), 0.60 (t, J= 7.6 Hz, 3H); LC-ELSD/MS purity 99%, MS ESI calcd. for C27H38N302 [M-H20+H]+ 436.3, found 436.3

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

Reference:
Patent; SAGE THERAPEUTICS, INC.; ROBICHAUD, Albert, Jean; SALITURO, Francesco, G.; BLANCO-PILLADO, Maria, Jesus; LA, Daniel; HARRISON, Boyd, L.; (276 pag.)WO2019/126741; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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 6314-23-4 as follows. Application In Synthesis of 2-(1-Pyrazolyl)ethanol

EXAMPLE 9: Synthesis of 5-amino-4-(6-methylpyridin-2-yl)-2-(2-pyrazol-1-yl-ethoxy)- thieno[2,3-d]pyrimidine-6-carboxamide (no. 27); 67 mg (0.60 mmol) of 1-(2-hydroxyethyl)-1H-pyrazole and 84 mg (0.75 mmol) of potassium tert-butoxide were added to a slurry of 174 mg (0.50 mmol) of 5-amino-2-methanesulfinyl-4- (6-methylpyridin-2-yl)thieno[2,3-d]pyrimidine-6-carboxamide in 1 ml of dioxane, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, which was then filtered with suction. The residue was washed with water, dried in vacuum and chromatographed on a silica-gel column with dichloromethane/methanol as eluent, giving 5-amino-4-(6-methylpyridin-2-yl)-2-(2-pyrazol-1 -yl-ethoxy)thieno[2,3- d]pyrimidine-6-carboxamide as red crystals; HPLC-MS: [M+H] 396. 1H-NMR (de-DMSO): delta [ppm] = 2.64 (s, 3H), 4.59 (t, J = 5.2 Hz, 2H), 4.83 (t, J = 5.2 Hz, 2H), 6.24 (t, J = 2 Hz, 1 H), 7.19 (bs, 2H), 7.46 (d, J = 2 Hz, 1 H), 7.57 (d, J = 7.7 Hz, 1 H), 7.81 (d, J = 2 Hz, 1 H), 8.04 (t, J = 7.8 Hz, 1 H), 8.20 (d, J = 7.9 Hz1 1 H), 8.38 (bs, 2H)

According to the analysis of related databases, 6314-23-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK PATENT GMBH; HOELZEMANN, Guenter; DORSCH, Dieter; GREINER, Hartmut; AMENDT, Christiane; ZENKE, Frank; WO2010/149257; (2010); 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. 49633-25-2, name is 3-Isopropylpyrazole, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 3-Isopropylpyrazole

A mixture of 2-chloro-4-fluoropyridine (23.88 g, 181.56 mmol), 3 -isopropyl -IH- pyrazole (20 g, 181.56 mmol), K2C03 (37.64 g, 272.34 mmol), and NMP (200 mL) was stirred at 100 C overnight under N2. The reaction mixture was allowed to cool to rt, poured into water (800 mL), and then extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (200 mL), dried over Na2S04, filtered, concentrated, and then purified by silica gel chromatography (petroleum ether/ethyl acetate=9/l) to give 2-chloro-4- (3-isopropyl-lif-pyrazol-l-yl)pyridine (9 g) as a colorless oil. 1H NIV1R (400MHz, CDCf): d 8.38 (d, 1H), 7.90 (d, 1H), 7.68 (d, 1H), 7.52 (d, 1H), 6.39 (d, 1H), 3.15-2.97 (m, 1H), 1.32 (d, 6H); LCMS: 222.1 [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 49633-25-2.

Reference:
Patent; METACRINE, INC.; SMITH, Nicholas D.; GOVEK, Steven P.; LAI, Andiliy G.; (0 pag.)WO2020/61118; (2020); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 5334-40-7, name is 4-Nitro-1H-pyrazole-3-carboxylic acid, 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 5334-40-7, Recommanded Product: 4-Nitro-1H-pyrazole-3-carboxylic acid

In a 250 mL round bottom flask, 5 g of crude I-j (18.1 mmol) was added. 4-nitro-1H-pyrazole-3-carboxylic acid 3.1 g (19.9 mmol), EDC·HCl 4.1g (21.7mmol), HOBt 2.9g (21.7mmol) and anhydrous DMF 50mL, Stir at room temperature for 24 h. The disappearance of the starting material by TLC (methanol: chloroform = 1:10). The reaction solution was poured into 200 mL of ice water. A large amount of pale yellow solid is precipitated, Rest, Thinking about a yellow solid, The obtained crude product was recrystallized from ethyl acetate and methanol to give (I-k) 4.7 g. The yield was 62.4%.

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; China Pharmaceutical University; Wang Yue; Lu Shuai; Zhi Yanle; Yao Chao; Lu Tao; Li Baoquan; Chen Puzhou; Bao Jiyin; (26 pag.)CN109970717; (2019); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 27258-33-9, These common heterocyclic compound, 27258-33-9, name is 1-Methyl-1H-pyrazole-5-carbaldehyde, 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.

(l-{4-[5-Amino-2-(3-trifluoromethoxy-phenyl)-pyrimidin-4-yl-amino]- phenyl}-cyclobutyl)-carbamic acid tert-butyl ester (200 mg 0.77 mmol) was dissolved in acetic acid (30 mL), then 2-Methyl-2H-pyrazole-3-carbaldehyde (93.5 mg, 0.85 mmol) and Cu(OAc)2 (140 mg, 0.77 mmol) were added separately. The reaction mixture was stirred at 100 C for 2 h. LC/MS showed there was about 40% desired product (l-{4-[8-(2-Methyl-2H-pyrazol-3-yl)-2-(3- trifluoromethoxy-phenyl)-purin-9-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester in the reaction mixture. Then the solvent was removed by concentration, and the residue was dissolved in ethyl acetate (150 mL). The organic layer was washed with sat. NaHC03 aqueous solution, followed by brine, dried over sodium sulfate, filtered and concentrated to give 150 mg of crude desired product with 80% purity, which was used directly without further purification. LC/MS (ESI+): e/z: 606.2 [M+l]+.

The synthetic route of 27258-33-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; SKELTON, Nicholas; GRADL, Stefan; BLAKE, James F.; GRAHAM, James M.; GUNAWARDANA, Indrani W.; HENTEMANN, Martin; MARLOW, Allison L.; TANG, Tony P.; WO2013/78254; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics