Day: June 17, 2021

These common heterocyclic compound, 687635-04-7, name is (3-(1H-Pyrazol-1-yl)phenyl)methanamine, 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. Safety of (3-(1H-Pyrazol-1-yl)phenyl)methanamine

To 3-pyrazol-1-yl-benzylamine (0.5 mmol) in THF (2 mL) at room temperature were added Iso-butylaldehyde (0.6 mmol) and anhydrous magnesium sulfate (60 mg). After stirring for 1.5 h at room temperature, sodium borohydride (0.5 mmol) was added and the mixture stirred for a further 2 h. Water (3 ml) was added to the mixture and stirring resumed for 10 min. Additional water was added (1 ml) and the mixture was extracted with CH2Cl2 (10 mL*3). After being dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure to give the crude product. This material was used in subsequent steps without further purification.

The synthetic route of (3-(1H-Pyrazol-1-yl)phenyl)methanamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dykes, Graeme James; Fletcher, Stephen Robert; Menet, Christel Jeanne Marie; Merayo, Nuria Merayo; Schmitt, Benoit Antoine; US2008/242661; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 3524-32-1, A common heterocyclic compound, 3524-32-1, name is 5-Amino-1,3-dimethylpyrazole, molecular formula is C5H9N3, 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: 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 synthetic route of 3524-32-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Chen, Hui; Shi, Daqing; Tetrahedron; vol. 67; 31; (2011); p. 5686 – 5692;,
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. 14884-01-6, name is 4-Methoxy-1H-pyrazole, A new synthetic method of this compound is introduced below., Recommanded Product: 14884-01-6

EXAMPLE 3 STR12 Process variant (a) 3.45 g (0.115 mol) of sodium hydride (80% pure) were introduced into a solution of 12.6 g (0.13 mol) of 4-methoxy-pyrazole in 100 ml of absolute dimethylformamide at room temperature and the mixture was subsequently warmed briefly to 60 C. 21.6 g (0.1 mol) of 3,7-dichloro-benzo-1,2,4-triazine 1-oxide were added in portions to the mixture, which had been cooled to room temperature. After the exothermic reaction had subsided, the mixture was subsequently stirred at 30 to 40 C. for a further 3 hours and the reaction product was then precipitated with water. This product was filtered off, stirred in 150 ml of methanol, filtered off again and dried. 17.3 g of 3-(4-methoxypyrazol-1-yl)-7-chloro-benzo-1,2,4-triazine 1-oxide of melting point 253-255 C. (with decomposition) were obtained, that is to say 62.3% of theory. The compound could be recrystallized from dimethylformamide.

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; Bayer Aktiengesellschaft; US4239760; (1980); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 37622-90-5,Some common heterocyclic compound, 37622-90-5, name is Ethyl 4-pyrazolecarboxylate, molecular formula is C6H8N2O2, 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.

Compound 103: 1-Methyl-1H-pyrazole-4-carboxylic acid ethyl ester. Under anhydrous condition, to a solution of ethyl 4-pyrazolecarboxylate (3.00 g) in DMF (210 mL, c=0.1 molL-1) cooled by an ice bath, NaH (in mineral oil 60%, 1.10 g, 1.3 equiv.) was added in 3 portions (over 5 minutes). The mixture was stirred for 15 minutes, then methyl iodide (1.6 mL, 1.2 equiv.) was added. The ice bath was removed, and the reaction was stirred at room temperature for 2 Hrs. The mixture was hydrolysed with a saturated aqueous solution of NaHCO3 (1.0 L) and extracted twice with EtOAc (2*1.5 L). The organic layers were combined, washed with brine (0.5 L), dried over MgSO4 and concentrated. Purification by flash-chromatography (AcOEt in cyclohexane, 0 to 90%) afforded compound 103 as a colourless oil in 79% yield (2.60 g). 1H-NMR (400 MHz, DMSO): 1.26 (t, J 7.1 Hz, 3H, O-CH2-CH3); 3.87 (s, 3H, N-CH3); 4.21 (q, J 7.1 Hz, 2H, O-CH2-CH3); 7.82 (s, 1H, Ar); 8.29 (s, 1H, Ar). M/Z (M+H)+ = 155.1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Ethyl 4-pyrazolecarboxylate, its application will become more common.

Reference:
Patent; Domain Therapeutics; Mayer, Stanislas; Schann, Stephan; EP2666775; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 4522-35-4,Some common heterocyclic compound, 4522-35-4, name is 3-Iodo-1H-pyrazole, molecular formula is C3H3IN2, 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.

Step C: 5-(3-Iodo-lH-pyrazol-l -yl)-3-(trifluoiOmethyl)pyridazine To 3-iodopyrazole (124 mg, 0.641 mmol) in DMF (2 mL)was added potassium tert- butoxide (53 mg, 0.472 mmol) at 0 C. The mixture was stirred at room temperature for 15 min. It was transfered into a solution of 5- chloro-3- (trifluoromethyl)pyridazine (78 mg, 0.427 mmol) in DMF (2 mL) at 0 C. It was wanned to room temperature, stirring for 30 min. It was diluted with EtOAc(20 mL), washed with water (3 x 20 mL), the combined aqueous layers were extracted with EtOAc (30 mL), the combined organic layers were washed with brine (30 mL), dried over Na2S04, filtered and concentrated. The residue was purified by flash chromatography (ISCO Combiflash, 12 g, 0-100% EtOAc in hexanes) to give a mixture of 3-iodopyrazole and the desired product (1 :2, 180 mg). It was disolved in anhydrous CH2C12 (2 mL) and added a little bit of DMAP and of di-fert-butyl dicarbonate (~ 100 mg). It was stirred at room temperature for 10 min and purified by flash chromatography (ISCO Combiflash, 0-40% EtOAc in hexanes) to give 5 -(3- iodo-lH-pyrazol-l-yl)-3-(trifluoromethyl)pyridazine, as white solid. LCMS calc. = 340.95, found = 340.84 (M+H)+. NMR (500 MHz, CHCl3-d): delta 9.78 (d, J= 2.5 Hz, 1 H); 8.17 (d, J= 2.5 Hz, 1 H); 8.04 (d, J= 2.7 Hz, 1 H); 6.84 (d, J = 2.7 Hz, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Iodo-1H-pyrazole, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MOCHIDA PHARMACEUTICAL CO., LTD.; SMITH, Cameron, James; TAN, John, Qiang; ZHANG, Ting; BALKOVEC, James; GREENLEE, William, John; GUO, Liangqin; XU, Jiayi; CHEN, Yi-heng; CHEN, Yili; CHACKALAMANNIL, Samuel; HIRABAYASHI, Tomokazu; NAGASUE, Hiroshi; OGAWA, Kouki; WO2014/120346; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 86477-09-0, 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 86477-09-0 as follows.

Example 162a 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic Acid 162a A 25-mL round-bottomed flask equipped with a reflux condenser was charged with ethyl 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylate (540 mg, 3.0 mmol), 2N Aqueous sodium hydroxide solution (3.5 mL), and 1,4-dioxane (3.0 mL). The system was heated at 65 C. for 2.5 h. It was then cooled to room temperature and adjusted the pH to 2-3 with concentrated HCl. The solid was collected by filtration to afford 162a (260 mg, 57%) as a yellow solid. MS-ESI: [M+H]+ 153.3

According to the analysis of related databases, 86477-09-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GENENTECH, INC.; Crawford, James John; Ortwine, Daniel Fred; Wei, BinQing; Young, Wendy B.; US2013/116246; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 23170-45-8, name is Methyl 3-methyl-1H-pyrazole-4-carboxylate, molecular formula is C6H8N2O2, 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: C6H8N2O2

A mixture of methyl 3-methyl- 1H-pyrazole-4-carboxylate (250.0 mg, 1.78 mmol), 4- isobutylphenyl boronic acid (412.9 mg, 2.32 mmol), pyridine (282.2 mg, 3.57 mmol) andcopper(II) acetate (486.0 mg, 2.68 mmol) in N,N-dimethylformamide (6 mL) was stirred at 25C for 14 h. The reaction was diluted with EtOAc (120 mL), washed with brine (50 mL x 3), dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (20% EtOAc in petroleum ether, Rf = 0.45) to give methyl 1-(4-isobutylphenyl)-3-methyl-1H-pyrazole-4- carboxylate (350 mg, 72% yield) as a white solid. LCMS (Method 5-95 AB, ESI): tR = 0.996mi [M+Hj = 272.9.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 23170-45-8, its application will become more common.

Reference:
Patent; RQX PHARMACEUTICALS, INC.; GENENTECH, INC.; CHEN, Yongsheng; SMITH, Peter Andrew; ROBERTS, Tucker Curran; HIGUCHI, Robert I.; PARASELLI, Prasuna; KOEHLER, Michael F. T.; SCHWARZ, Jacob Bradley; CRAWFORD, James John; LY, Cuong Q.; HANAN, Emily J.; HU, Huiyong; YU, Zhiyong; (424 pag.)WO2017/84630; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 34334-96-8, These common heterocyclic compound, 34334-96-8, name is 3-Methyl-5-nitro-1H-pyrazole, 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: The reaction was performed in 2 batches. In a sealed tube, cyanomethylenetributyl phosphorane (9.28 mL, 35.40 mmol) was added to a solution of 3-methyl-5-nitro-lH- pyrazole (1.50 g, 1 1.80 mmol) and 3-hydroxymethyl-3-methyloxethane (3.53 mL, 35.40 mmol) in toluene (100 mL). The solution was heated at 60 C for 18 h. The 2 batches were combined and the solvent was evaporated in vacuo. The residue (black oil) was purified by column chromatography on silica gel (irregular SiOH, 15-40 muiotaeta, 330 g, liquid loading on DCM, mobile phase: heptane/EtOAc, gradient from 90: 10 to 50:50). The fractions containing the product were combined and evaporated to dryness to give 3.95 g of intermediate 303 (79% yield, orange oil) directly used as it in the next step.

The synthetic route of 34334-96-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; STANSFIELD, Ian; QUEROLLE, Olivier, Alexis, Georges; LIGNY, Yannick, Aime, Eddy; GROSS, Gerhard, Max; JACOBY, Edgar; MEERPOEL, Lieven; GREEN, Simon, Richard; HYND, George; KULAGOWSKI, Janusz, Jozef; MACLEOD, Calum; MANN, Samuel, Edward; (472 pag.)WO2018/2217; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 1072-68-0, 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.

Intermediate 7: 1,4-Dimethyl-1H-pyrazole-5-sulfonyl chlorideA solution of 23% n-butyl lithium in hexane (17.3 mL, 1.2 eq) was added drop-wise to a solution of 1,4-dimethyl-1H-pyrazole (5 g, 1 eq.) in dry ether (50 mL) at -65 C. under a nitrogen atmosphere. The temperature of the resulting suspension was raised to 0 C. temperature over 1 hour and then cooled to -70 C. Excess sulfur dioxide was bubbled to the mixture for 30 minutes, while maintaining the temperature below -65 C. The solution was stirred at -65 C. for 1 hour and was then allowed to warm to room temperature. The resulting precipitate was filtered, washed with ether and dried to yield the lithium sulfinate salt of 1,4-dimethyl-1H-pyrazole. [0570] 1H NMR (400 MHz, DMSO-d6) delta ppm 2.03 (s, 3H) 3.87 (s, 3H) 6.94 (s, 1H)

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

Reference:
Patent; Carroll, Colm; Goldby, Anne; Teall, Martin; US2013/324576; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 5744-59-2, 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. 5744-59-2, name is 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Step (b) N-((ls,4s)-4-(l,5-dimethyl-lH-pyrazole-3-carboxamido)cyclohexyl)-5-fluoro-2- (3-iodophenoxy)nicotinamide To a suspension of N-((ls,4s)-4-aminocyclohexyl)-5-fluoro-2-(3-iodophenoxy Nicotinamide hydrochloride (1.5 g, 3.05 mmol) in acetonitrile (100 mL) was added 1,5-dimethyl-lH- pyrazole-3-carboxylic acid (1.069 g, 7.63 mmol) and triethylamine (4.25 mL, 30.50 mmol). 1- Propanephosphonic acid cyclic anhydride, 1.57M solution in THF (T3P) (5.83 mL, 9.15 mmol) was then added and the mixture stirred at RT for 2 h. The mixture was evaporated to dryness and the residue dissolved in DCM (150 mL) and washed with saturated NaHCO3 (aq), brine, dried (MgSO4) and evaporated to give a foam. The product was purified using column chromatography (eluent = neat EtOAc) to give the sub-title compound as a white foam. Yield: 1.04 g1H NMR (400 MHz, CDCl3) delta 8.36 (dd, J= 8.2, 3.1 Hz, IH), 8.07 (d, J= 3.1 Hz, IH), 7.87 (d, J= 6.7 Hz, IH), 7.64 (dt, J= 7.5, 1.5 Hz, IH), 7.55 (t, J= 1.8 Hz, IH), 7.22 – 7.14 (m, 2H), 6.69 (d, J= 7.7 Hz, IH), 6.53 (s, IH), 4.26 – 4.17 (m, IH), 4.12 – 4.03 (m, IH), 3.78 (s, 3H), 2.28 (s, 3H), 1.95 – 1.73 (m, 6H), 1.67 – 1.58 (m, 2H) MS: [M+H]+ = 578 (MultiMode+).

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

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/144494; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics