Category: pyrazoles-derivatives

Reference of 4058-91-7,Some common heterocyclic compound, 4058-91-7, name is 5-Amino-1-methyl-1H-pyrazole-4-carboxylic acid, molecular formula is C5H7N3O2, 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.

To a stirred solution of Step 3 intermediate (800 mg, 5.666 mmol) in dry DMF (8 ml), 2-bromo- l-(2-chlorophenyl)ethanone (1.32 g, 5.666 mmol) was added followed by potassium fluoride (500 mg, 8.499 mmol) at room temperature and the resultant reaction mixture was stirred overnight. The mixture was quenched with water (75 mL) and ethyl acetate (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water (2 x 100 mL) and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue obtained was purified by flash silica gel column chromatography to afford 912 mg of the desired product as a solid. lH NMR (300 MHz, DMSO-d6): delta 3.54 (s, 3H), 5.31 (s, 2H), 6.31 (s, 2H), 7.43-7.53 (m, 1H), 7.55 (d, = 4.8 Hz, 1H), 7.77 (d, = 7.5 Hz, 2H), 7.95 (s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Amino-1-methyl-1H-pyrazole-4-carboxylic acid, its application will become more common.

Reference:
Patent; GLENMARK PHARMACEUTICALS S.A.; KUMAR, Sukeerthi; CHAUDHARI, Sachin Sundarlal; GHARAT, Laxmikant Atmaram; KHAIRATKAR-JOSHI, Neelima; SHAH, Daisy Manish; MUKHOPADHYAY, Indranil; (327 pag.)WO2018/203298; (2018); A1;,
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Synthetic Route of 7119-95-1,Some common heterocyclic compound, 7119-95-1, name is 1-Nitropyrazole, molecular formula is C3H3N3O2, 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 15 (E)-4-{3-[2-(3-Chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester A solution of 1-nitro-1H-pyrazole (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-Nitro-1H-pyrazole (3.16 g, 79percent): H1-NMR (400 MHz, DMSO-d6) delta7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz).

The synthetic route of 7119-95-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Berthel, Steven Joseph; Kester, Robert Francis; Murphy, Douglas Eric; Prins, Thomas Jay; Ruebsam, Frank; Tran, Chinh Viet; Vourloumis, Dionisios; US2008/146625; (2008); A1;,
Pyrazole – Wikipedia,
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Synthetic Route of 120068-79-3, These common heterocyclic compound, 120068-79-3, name is 5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile, 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.

General procedure: Phenylpyrazole (0.2 mmol), arylboronic acid (0.4 mmol), NIS (0.2 mmol), [Pd] (10 mol%), NaHCO3 (0.4 mmol) and C2H5OH:H2O (3:1, 10 mL), were added to a Schlenk tube. Then the tube was charged with N2 and the reaction mixture was stirred at 80 C for 18 h. After the completion of the reaction, as monitored by TLC, the mixture was cooled and filtrated. The filtrate was extracted with ethyl acetate and washed with brine. Then the combined organic extracts were dried over Na2SO4, concentrated under vacuum and the resulting residue was purified by silica gel column chromatography to afford the desired products.

Statistics shows that 5-Amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-1H-pyrazole-3-carbonitrile is playing an increasingly important role. we look forward to future research findings about 120068-79-3.

Reference:
Article; Lv, Ting; Zhang, Xiao-Hong; Han, Jiang-Sheng; Zhong, Ping; Journal of Fluorine Chemistry; vol. 137; (2012); p. 44 – 49;,
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Synthetic Route of 152120-54-2, These common heterocyclic compound, 152120-54-2, name is tert-Butyl (((tert-butoxycarbonyl)amino)(1H-pyrazol-1-yl)methylene)carbamate, 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.

A solution of (1S,2R)-1-((2R,3R,4S)-3-acetamido-4-azido-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (5.1 g, 11.5 mmol) in ethanol (300 mL) was hydrogenated with Lindlar’s catalyst for 8 h (1 atmospheric pressure). The reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in THF (50 mL). This solution was mixed with tert-butyl (((tert-butoxycarbonyl)amino)(1H-pyrazol-1-yl)methylene)carbamate (13.1 g, 42.21 mmol) and the resulting reaction mixture was stirred at room temperature for 18 h. It was then diluted with aq. NH4Cl and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Purification by silica gel chromatography (gradient elution, 1:1 EtOAc/pentane to 100% EtOAc) to afford 4.0 g of (1S,2R)-1-((2R,3R,4S)-3-acetamido-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (50%). (1S,2R)-1-((2R,3R,4S)-3-Acetamido-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (4.0 g, 5.94 mmol) was dissolved in methanol (20 mL) and treated with 1N NaOH (6 mL) with cooling in an ice-bath. The reaction was stirred for 30 min and neutralized with 1N HCl. Then the reaction was concentrated under reduced pressure and the residue was re-dissolved in methanol and filtered. The filtrate was concentrated under reduced pressure to afford 3.0 g of (2R,3R,4S)-3-acetamido-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-2-((1S,2R)-1,2,3-triacetoxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid (95%).

The synthetic route of 152120-54-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Catabasis Pharmaceuticals, Inc.; Milne, Jill C.; Jirousek, Michael R.; Vu, Chi B.; Wensley, Allison; Ting, Amal; (180 pag.)US2016/129122; (2016); A1;,
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Synthetic Route of 37718-11-9, These common heterocyclic compound, 37718-11-9, name is 1H-Pyrazole-4-carboxylic acid, 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.

To a mixture of lH-pyrazole-4-carboxylic acid (5.00 g, 44.6 mmol) in dry CH3OH (100 mL) was added drop-wise H2S04 (874 mg, 8.92 mmol) at 0C. The mixture was stirred at reflux overnight. A solution of NaOH (3.83 g, 95.7 mmol, 10 N) was added drop- wise to the reaction mixture. The mixture was poured into ice-water and diluted with ethyl acetate. The organic layer was washed with saturated aqueous lithium chloride solution and brine successively, dried over anhydrous Na2SC>4 and concentrated. The residue was purified by silica gel chromatography (petroleum ether : ethyl acetate = 10 : 1) to give methyl 1H- pyrazole-4-carboxylate (4.50 g) as a white solid. LC-MS (ESI) found: 127 [M+H]+.

The synthetic route of 37718-11-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ZAFGEN, INC.; ZAHLER, Robert; VATH, James E.; (130 pag.)WO2018/31877; (2018); A1;,
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Adding a certain compound to certain chemical reactions, such as: 175277-11-9, name is 3-tert-Butyl-1-methylpyrazole-5-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 175277-11-9, name: 3-tert-Butyl-1-methylpyrazole-5-carboxylic Acid

27) 3-(tert-butyl)-N-(3-methoxy-4-methylbenzyl)-1-methyl-1H-pyrazole-5-carboxamide To a solution of 3-Methoxy-3-methyl-benzaldehyde (250 mg, 1.66 mmol, 1.0 eq) in toluene (20 mL) was added 2,4-dimethoxybenzyl amine (306 mg, 1.83 mmol, 1.1 eq) and the reaction mixture was stirred at room temperature for 24 h. Toluene was removed to give a residue, which was taken in MeOH (20 mL) and then NaBH4 (129 mg, 3.32 mmol, 2.0 eq) was added slowly. The reaction mixture was stirred at room temperature for 6 h. Solvent was removed and the residue was extracted in Ethyl acetate and stirred with saturated aq NaHCO3 for 1 h. The organic layer was collected, dried and solvent was removed to give the crude amine, which was used in the next step without further purification. To a solution of the crude amine (1.66 mmol, 1.0 eq) in DMF (20 mL) were added the acid (333 mg, 1.83 mmol, 1.1 eq), DIEA (1.07 g, 8.32 mmol, 5 eq) and HBTU (757 g, 1.99 mmol, 1.2 eq) and the reaction mixture was stirred at rt for 12 h. The reaction mixture was then diluted with ethyl acetate (75 mL) and washed with 10% aqHCl (1*50 mL), sat NaHCO3 (1*50 mL) and water (4*50 mL). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was purified by column chromatography (EtOAc/Hexane 25% to 75%)) to give the amide, which was directly used in the next step. The amide was treated with 95% TFA:H2O for 12 h. TFA was removed and azeotroped with toluene to give a residue, which was purified by column chromatography (EtOAc/Hexane 10% to 50%) to give the desired product in (263 mg, >95% purity). Mass Spectrum (LCMS, ESI Pos.) Calcd. For C18H26N3O2: 316.0 (M+H), Found 316.0.

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, 3-tert-Butyl-1-methylpyrazole-5-carboxylic Acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Prosetta Antiviral ,Inc.; Selvarajah, Suganya; Paulvannan, Kumar; (58 pag.)US2018/118679; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 52867-42-2, name is Methyl 2-methyl-5-oxo-2,5-dihydro-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 52867-42-2, Product Details of 52867-42-2

Methyl-3-(difluoromethoxy)-1-methyl-1H-pyrazole-5-carboxylate A solution of 2.00 g (12.8 mmol) of methyl 3-hydroxy-1-methyl-1H-pyrazole-5-carboxylate (preparation: Chem. Ber. 1974, 107, 1318-1328) in 28 ml of N,N-dimethylformamide is admixed with 5.09 g (32.0 mmol, 96%) of chlorodifluoroacetic acid sodium salt and 2.66 g (19.2 mmol) of potassium carbonate, and the reaction mixture is heated at 80 C. overnight. The reaction mixture is added to 300 ml of water and extracted several times with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and concentrated by evaporation in vacuo on a rotary evaporator. Chromatographic purification gives 1.07 g of methyl-3-(difluoromethoxy)-1-methyl-1H-pyrazole-5-carboxylate (40%). 1H-NMR (400 MHz, d6-DMSO): delta=7.19 (t, 1H), 6.55 (s, 1H), 4.00 (s, 3H), 3.55 (s, 3H) ppm. HPLC-MS: log P=2.04; mass (m/z)=207 [M+H]+.

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 2-methyl-5-oxo-2,5-dihydro-1H-pyrazole-3-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Bayer CropScience AG; US2011/301181; (2011); A1;,
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Some common heterocyclic compound, 10250-64-3, name is 1-Methyl-3-phenyl-1H-pyrazole-5-carboxylic acid, molecular formula is C11H10N2O2, 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. Computed Properties of C11H10N2O2

To a stirred suspension of 1-methyl-3-phenyl-1H-pyrazole-5-carboxylic acid (46 mg, CAS 10250-64-3) in dichloroethane (2 ml) were added oxalyl chloride (44 mul) and DMF (2 drops). The reaction mixture was stirred at room temperature for 1 h and was then concentrated in vacuo. The residue was dissolved in THF (1 ml) and the resulting solution was added dropwise to a stirred solution of (+)-(R)-2-(4-amino-3-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (50 mg, example 1h) and triethylamine (118 mul) in THF (2 ml). The reaction mixture was stirred at room temperature for 2 h. The crude reaction mixture was then concentrated in vacuo and the residue was purified by column chromatography (SiO2; gradient: 0% to 50% EtOAc in heptane) to give (R)-2-{3-fluoro-4-[(2-methyl-5-phenyl-2H-pyrazole-3 carbonyl)-amino]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (81 mg, quant.) as a white solid. MS (ISP): 503.1 ([M+Na]+), 481.3 ([M+H]+), 425.2 ([M+H-C4H8]+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 10250-64-3, its application will become more common.

Reference:
Patent; Galley, Guido; Norcross, Roger; Pflieger, Philippe; US2012/316165; (2012); A1;,
Pyrazole – Wikipedia,
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Electric Literature of 155377-19-8, A common heterocyclic compound, 155377-19-8, name is Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate, molecular formula is C7H7F3N2O2, 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.

According to the procedure of Buchwald et al . (J. Org. Chem. 2004, 69, 5578), to a 50 mL sealed tube flushed with argon were added copper (I) iodide (0.02288 g, 0.1201 mmol) , K2CO3 (0.6972 g, 5.045 mmol), and ethyl 3- (trifluoromethyl) -IH- pyrazole-4-carboxylate (0.500 g, 2.402 mmol). ( IS, 2S) -N1,N2- Dimethylcyclohexane-1, 2-diamine (0.06834 g, 0.4805 mmol) and 2-bromophenol (0.3343 mL, 2.883 mmol) were then added along with 3 mL of toluene (degassed under argon) . The tube was sealed and heated to 1100C overnight, then cooled to room temperature and the mixture was filtered through celite to remove the solid. The filtrate was concentrated under vacuum and the residue was purified by chromatography (10% ether/DCM) to give ethyl 1- (2-hydroxyphenyl) -3- (trifluoromethyl) -IH- pyrazole-4-carboxylate (0.660 g, 91%) as a solid: 1H NMR (400 MHz, CDCl3) delta 1-40 (t, 3H, J = 7.0 Hz), 4.39 (q, 2H, J = 7.0 Hz), 7.00 (m, IH), 7.16 (m, IH), 7.31 (m, IH), 7.42 (m, .1H), 8.56 (m, IH).

The synthetic route of 155377-19-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2008/11130; (2008); A2;,
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Adding a certain compound to certain chemical reactions, such as: 70951-85-8, name is 4-Bromo-1-(tert-butyl)-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 70951-85-8, HPLC of Formula: C7H11BrN2

Stage d) Preparation of 1-(1,1-Dimethylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Intermediate 11) To a 20 L four-neck bottle, 4-bromo-(tert-butyl)pyrazole (1.15 kg, 5.66 mol) and THF (9.2 L) were added, then the mixture was cooled to between -78 C. and -85 C. and treated with nBuLi (6.23 mol) dropwise at that temperature. After addition the solution was stirred at the same temperature for 1 h and isopropyl pinacol borate (1.47 kg, 7.92 mol) was added dropwise. The reaction was complete after stirring for ?3 h (starting material<1.0% a/a by GC) then water (2.3 L) was added to quench the reaction; and the pH adjusted to 8-9 by addition of 3.45 kg 1M HCl. The aqueous phase was extracted with TBME (3.45 L*2), and the combined organic phase washed with 5% NaCl (3.45 L*2) and water (3.45 L) in sequence. The organic phase was evaporated to give the crude product. After subsequent recrystallization from heptanes the pure product was obtained as a white solid (GC purity 99.7% a/a) in a 63.5% th overall yield. (Two 20 L reactions were run, then combined in the heptane recrystallization). 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; GLAXO GROUP LIMITED; Atkinson, Francis Louis; Barker, Michael David; Douault, Clement; Garton, Neil Stuart; Liddle, John; Patel, Vipulkumar Kantibhai; Preston, Alexander George Steven; Wilson, David Matthew; US2013/40984; (2013); A1;,
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Pyrazoles – an overview | ScienceDirect Topics