Category: pyrazoles-derivatives

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. 25016-12-0, name is 1,3-Dimethyl-1H-pyrazole-4-carbaldehyde, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

To a suspension of tert-butyl 5-((2-amino-5-chloro-3-nitropyridin-4- yl)amino)hexahydrocyclo- penta[c]pyrrole-2(lH)-carboxylate (0.62 g, 1.60 mmol) and 1,3- dimethylpyrazole-4-carbaldehyde (0.22 g, 1.78 mmol) in EtOH (30.0 mL) was added a freshly prepared aqueous solution of sodium dithionite (6.30 mL, 6.30 mmol, 1.0 mol/L). The mixture was heated at 85 C overnight. The mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v) = 50/1 to 30/1 to 20/1) to afford the title compound as a white solid (0.50g, yield 68%).MS (ESI, pos. ion) m/z: 472.3 [M+H]+; MR (600 MHz, CDC ) delta (ppm): 7.87 (s, 1H), 7.72 (s, 1H), 5.49 – 5.39 (m, 1H), 5.03 (d, J = 8.4 Hz, 1H), 3.92 (s, 3H), 3.58 – 3.48 (m, 2H), 3.46 – 3.33 (m, 2H), 2.80 – 2.72 (m, 2H), 2.69 – 2.60 (m, 5H), 1.50 (s, 9H), 1.48 – 1.40 (m, 2H).

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; SUNSHINE LAKE PHARMA CO., LTD.; CALITOR SCIENCES, LLC; XI, Ning; LI, Xiaobo; LI, Mingxiong; ZHANG, Tao; HU, Haiyang; WU, Yanjun; (139 pag.)WO2018/169700; (2018); 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. 1572-10-7, name is 3-Amino-5-phenylpyrazole, This compound has unique chemical properties. The synthetic route is as follows., Safety of 3-Amino-5-phenylpyrazole

General procedure: The compound tetronic acid (15) (80 mg, 0.8 mmol) was dissolved in 4 mL of ethanol, followed by addition of terphenyl aldehyde 13a (221.2 mg, 0.8 mmol) and 3-amino-5-phenyl pyrazole 14a (127.2 mg, 0.8 mmol). The reaction mixture was refluxed in ethanol at 78 C for an hour. Then reaction suspension was cooled to room temperature, and the precipitated product was collected by vacuum filtration and washed with ethanol (3 mL), then recrystallized from ethanol to afford pure compound 8a as a white solid, 340 mg in 85% yield. Mp: 273-274 C; 1H NMR (300 MHz, DMSO-d6): delta 4.80 (s, 2H), 5.25 (s, 1H ), 6.89-6.99 (m, 1H), 7.19-7.35 (m, 7H), 7.42-7.52 (m, 4H), 7.65 (dd, 4H, J = 8.8, 11.7 Hz), 8.05 (s, 1H), 10.19 (s, 1H ), 12.56 (s, 1H); 13C NMR (300 MHz, DMSO-d6): delta 30.5, 64.8, 94.4, 99.8, 111.1, 111.3, 113.2, 121.3, 125.4, 126.1, 126.7, 126.9, 127.1, 127.2, 127.3, 128.3, 128.7, 128.8, 132.7, 137, 137.2, 138.8, 139.3, 145.8, 152.7, 157.7, 172.2; MS (ESI): 500 [M+H]+; HRMS (ESI) calcd for C32H23O2N3F [M+H]+ 500.1712; found: 500.1738.

According to the analysis of related databases, 1572-10-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kamal, Ahmed; Tamboli, Jaki R.; Lakshma Nayak; Adil; Vishnuvardhan; Ramakrishna; Bioorganic and Medicinal Chemistry; vol. 22; 9; (2014); p. 2714 – 2723;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 105434-90-0, name is Ethyl 5-amino-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. Formula: C6H9N3O2

Ethyl 5-amino-1H-pyrazole-3-carboxylate (1.55 g, 10 mmol), tert-butyl acetoacetate (1.65 mL, 10 mmol), 3-fluoro-(4-trifluoromethyl)benzaldehyde (1.92 g, 10 mmol) and sodium bicarbonate (2.52 g, 30 mmol) were heated at 70 C. in DMF (3 mL) overnight. The reaction mixture was allowed to cool then partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was further extracted with ethyl acetate (20 mL) and the combined organics were dried by passing through a hydrophobic fit, and evaporated to give an orange oil. The residue was dissolved in a minimum amount of DCM and loaded onto a 50 g Si cartridge. The product was eluted with 0-50% ethyl acetate in cyclohexane. The fractions containing the desired product were combined and evaporated to give a pale yellow solid. The solid was triturated with ethyl acetate/cyclohexane to give a white solid (1.25 g). LCMS (Method 3): Rt=1.36 min, m/z 470.5 [M+H]+

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

Reference:
Patent; CHIESI FARMACEUTISI S.p.A.; Accetta, Alessandro; Rancati, Fabio; Capelli, Anna Maria; Clark, David Edward; Tisselli, Patrizia; Edwards, Christine; Bhalay, Gurdip; (97 pag.)US2018/170939; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 285984-25-0, 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.

Preparation 38 5-fert-butyl-2- g-tolyl-2i7-pyrazol-3-ylVcarbamic acid. 2.2.2-trichloro-ethyl ester Add a saturated solution OfNa2CO3 (2.4 L) to a solution of 5-tert-butyl-2-/>-tolyl-2.ff-pyrazol-3- ylamine (400 g, 1.74 mol) in THF (8L) and cool the mixture to 0 C. Then dropwise add 2, 2, 2- trichloroethyl chloroformate (406.77 g, 1.92 mol) and stir the mixture at 0 C for 2 hours. Extract the reaction mixture with ethyl acetate (3 x 6.5L), dry over anhydrous magnesium sulfate and concentrate. Dissolve the solid in a minimal amount of ethyl acetate and add an excess of hexanes to precipitate. Collect the solid by filtration and dry to obtain the title compound as an off white solid (586 g, 83% yield). 1H NMR (400 MHz, CDCl3) delta 7.34 (d, 2H), 7.29 (d, 2H), 6.78 (bs, IH), 6.41 (bs, IH), 4.81 (s, 2H), 2.41 (s, 3H), 1.34 (s, 9H). MS(ES+): m/? = 406.1 [M+H].

The synthetic route of 285984-25-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2007/53394; (2007); A1;,
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

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

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

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

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

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