Month: April 2021

Electric Literature of 930-36-9, 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 930-36-9 as follows.

The 6-[4-[4-[2-(l-methyl-lH-pyrazol-5-yl)ethoxy]phenyl]piperidin-l-yl]-3-(trifluoromethyl)[l,2,4]triazolo[4,3-b]pyridazine used as starting material was prepared as follows :-; Preparation of 2-(l-methyl-lH-pyrazol-5-yl)ethanol n-Butyl lithium (1.6M in hexanes) (1226 mL, 1961.78 mmol) was added dropwise to 1- methyl-lH-pyrazole (153.4 g, 1868.37 mmol) in THF (3000 mL) cooled to -78C over a period of 1 hour under nitrogen. The resulting solution was stirred at -600C for 30 minutes, then warmed to -100C and stirred for a further 40 minutes. A solution of oxirane (210 mL, 4203.82 mmol) in THF (600 mL) was added slowly at – 100C followed by further THF (1000 mL) and the resulting slurry was stirred at -100C for 30 minutes, then at 00C for 30 minutes. The mixture was then allowed to gradually warm to room temp under nitrogen and stirred for 16 hours. The reaction mixture was quenched with saturated NH4CI solution (2000 ml), the layers separated and the aqueous phase extracted with n-butanol (3 x 1000 ml). The combined organics were washed with saturated brine (1500 ml), dried over MgSOphi filtered and evaporated to give an oil, which was azeotroped with toluene(1000 ml) to leave an oil with some solid. The oil was dissolved in DCM and the insoluble solid was filtered off and washed with DCM. The filtrate was purified by chromatography using a silica Novasep prep HPLC column, eluting with a gradient of 5-10% methanol in DCM. Pure fractions were evaporated to dryness to afford 2-(l-methyl-lH-pyrazol-5- yl)ethanol (195 g, 83%) as an oil.IH NMR (400.1 MHz, DMSO-d6) delta 2.77 (2H, t), 3.63 (2H, m), 3.74 (3H, s), 4.74 (IH, t), 6.04 (IH, m), 7.26 (IH, d).

According to the analysis of related databases, 930-36-9, the application of this compound in the production field has become more and more popular.

Some common heterocyclic compound, 51516-67-7, name is 5-Amino-1-(4-chlorophenyl)-1H-pyrazole-4-carbonitrile, molecular formula is C10H7ClN4, 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: C10H7ClN4

Example 9: Synthesis of 4-imino-l-phenyl-5-(2,3,6-trifluorophenyl)-4,5-dihydro-lH- pyrazolor3,4-dlpyrimidine-6(7H)-thione (A575 (33)):Synthesis of 4-imino-l-phenyl-5-(2,3,6-trifluorophenyl)-4,5-dihydro-lH-pyrazolor3,4- dlpyrimidine-6(7H)-thione (A575 (33)). A mixture of 5-amino-l -phenyl- lH-pyrazole-4 carbonitrile (218 mg, 1 mmol) and l,3,4-trifluoro-2-isothiocyanatobenzene (189 mg, 1 mmol) was refluxed for 2h,and then cooled. Intermediate was precipitated spontaneously and were collected as pure products (M+l)+ = 408 (325 mg, white solid, 80%). Then using the same procedure as that of A348 (13) to synthesis compound (A575 (33)) (M+l)+ = 498.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 51516-67-7, its application will become more common.

Reference of 5334-39-4, 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 5334-39-4 as follows.

: To a solution of l-ethyi-5-hydroxy-piperidin-2-one (530 mg, 3.70 mmol), 3-methyl-4-nitro-lH-pyrazole (706 mg, 5.55 mmol) and PPrn (i ,46 g, 5.55 mmol) in THF (20 mL) was added dropwise DIAD (1.12 g, 5.55 mmol ) at 0 C over 20 min. After addition, the mixture was stirred at this temperature for 40 min, and then the resulting mixture was stirred at 20 C for 1 1 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE:EtOAc = 5: 1 to 0: 1) to give a mixture of l-ethyl-5-(5-methyl-4-nitro-lH-pyrazol-l- yi)piperidin-2~one and l~ethyl-5-(3~methyl-4-nitro-lH~pyrazol-l~yl)piperidin~2-one as a yellow solid. LCMS: RT 0.881 min, m/z = 253.1 [M+H]+

According to the analysis of related databases, 5334-39-4, the application of this compound in the production field has become more and more popular.

These common heterocyclic compound, 92933-47-6, name is 5-Isopropyl-1H-pyrazole-3-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. name: 5-Isopropyl-1H-pyrazole-3-carboxylic acid

Step 4 (R)-3-bromo-l-(1-(3-isopropyl-IH-pyrazole-5-earbonyl)pyrrolidin-3-yl)pyridin-2(lII)-onemixture of (R)-3-bromo-1-(pyrrolidin-3-yl)pyridin-2(1J])-one (3 g, 12.34 mmol), 3-isopropyl- 11-1-pyrazole-5-carboxylic acid (2.1 g, 13.58 mmol), HATU (5.6 g, 14.8 Immol) and DIEA (6.5837.02 mmol) in DMF (30 rnL) was stirred at room temperature for 12 hrs. The mixture wasdiluted with EtOAc (60 mL), washed with brine (60 mL x 2). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude residue was purified by preparative TLC (DCM: MeOH = 50: 1) to afford the desired product (1.6 g, 34% yield) as a light yellow solid. LCMS M/Z (M+Na) = 402.8.

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

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. 133228-21-4, name is N,N-Dimethyl-1H-pyrazole-1-sulfonamide, This compound has unique chemical properties. The synthetic route is as follows., name: N,N-Dimethyl-1H-pyrazole-1-sulfonamide

To a solution [OF N-DIMETHYLSULFAMOYLPYRAZOLE] (44.0 g, 0.251 mol) in dry tetrahydrofuran (500 mL) at-78 C was added dropwise a solution of n-butyllithium (2.5 M in hexane, 105.5 mL, 0.264 mol) while maintaining the temperature [BELOW-60 C.] A thick solid formed during the addition. Upon completion of the addition the reaction mixture was maintained for an additional 15 minutes, after which time a solution of 1,2-dibromo- tetrachloroethane (90 g, 0.276 mol) in tetrahydrofuran (150 mL) was added dropwise while maintaining the temperature below-70 [C.] The reaction mixture turned a clear orange; stirring was continued for an additional 15 [MINUTES. THE-78 C] bath was removed and the reaction was quenched with water (600 mL). The reaction mixture was extracted with methylene chloride (4x), and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride-hexane (50: 50) as eluent to afford the title product as a clear colorless oil (57.04 g). 1H NMR [(CDC13)] [8] 3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m, 1H).

According to the analysis of related databases, 133228-21-4, the application of this compound in the production field has become more and more popular.

These common heterocyclic compound, 3469-69-0, name is 4-Iodopyrazole, 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. Computed Properties of C3H3IN2

Example 2: 4-((?)-2-(l-((2/?,3i?)-3-(2,4-Difluorophenyl)-3-hydroxy-4- (l/T-l,2,4-triazol-l-yl)butan-2-yl)-lflr-pyrazol-4-yl)vinyl)benzonitrileStep 1 : l-(l-Ethoxyethyl)-4-iodo-l//-pyrazole; 4-1OdO-IiZ-PyTaZoIe (3.Og) was suspended in benzene (15OmL) and the suspension was heated while stirring. Ethyl vinyl ether (4.4mL) was added thereto, concentrated HCl was added dropwise thereto, and the resulting mixture was stirred at 60 C for 3 hours. After completion of the reaction, the resulting mixture was concentrated by evaporation under a reduced pressure, and the residue was neutralized using aqueous saturated sodium hydrogen carbonate (1OmL). The resulting mixture was extracted with ethyl acetate (5OmL) and the extract was washed successively with distilled water (10OmL). The organic layer was dried over anhydrous magnesium sulfate and concentrated by evaporation under a reduced pressure. The resulting residue was purified by silica gel chromatography to obtain the title compound as a transparent yellow liquid (3.Og, yield 73%). 1H NMR (CDCl3): delta 7.54(s, IH), 7.41(s, IH), 5.40(q, IH, /=6.0 Hz), 3.38-3.18(m, 2H), 1.54(d, 3H, /=6.0 Hz), 1.05(t, 3H, /=7.1 Hz).

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

Adding a certain compound to certain chemical reactions, such as: 35344-95-7, name is 1H-Pyrazole-4-carbaldehyde, 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 35344-95-7, category: pyrazoles-derivatives

NaH (60% in oil, 79 mg, 2.0 mmol) was added to a solution of Intermediate 7(172 mg, 1.79 mmol) in DMF (18 mL) at 0C, and the reaction was allowed to stir at 0Cfor 15 minutes. A solution of 4-(bromomethyl)-1,1?-biphenyl (442 mg, 1.79 mmol) in 5mL of DMF was then added at 0C. The reaction stirred at 0 C for 1.5 hours, then allowed to warm to rt, and stirred for 5 minutes before quenching with water. The reaction was diluted with EtOAc, washed with 10% aq. LiC1 solution and brine, dried with Na2SO4, filtered and concentrated. The crude mixture was purified by silica gelchromatography to yield 39A (424 mg, 90.3%) as a white solid. MS(ESI) m/z 397.9 (M+H)h

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1H-Pyrazole-4-carbaldehyde, and friends who are interested can also refer to it.

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. 1192-21-8, name is 1-Methyl-1H-pyrazol-5-amine, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 1192-21-8

2nd Generation XantPhos precatalyst (26.4 mg, 0.03 mmol) was added to (5)-2-(2,5- dichloropyrimidin-4-yl)-6-methyl-7-((6-methylpyridin-2-yl)methyl)-6,7- dihydroimidazo[l,2-a]pyrazin-8(5H)-one (Intermediate 46; 120 mg, 0.30 mmol), 1-methyl- lH-pyrazol-5-amine (72.2 mg, 0.74 mmol) and Cs2C03 (194 mg, 0.60 mmol) in 1,4- dioxane (8 mL) at 25 ¡ãC under nitrogen. The resulting mixture was stirred at 100 ¡ãC for 8 hours. The solvent was then removed under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 6percent MeOH in DCM. Pure fractions were evaporated to dryness to afford a yellow residue. This residue was further purified by preparative HPLC (XSelect CSH Prep CI 8 OBD column, 5mu silica, 19 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.03percent NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (5)-2-(5-chloro-2-((l-methyl-lH-pyrazol-5-yl)amino)pyrimidin-4-yl)-6- methyl-7-((6-methylpyridin-2-yl)methyl)-6,7-dihydroimidazo[l,2-a]pyrazin-8(5H)-one (Example 11; 50 mg, 36.2percent) as a white solid. H NMR (400 MHz, DMSO, 22 ¡ãC) delta 1.19 (3H, d), 2.47 (3H, s), 3.70 (3H, s), 4.08 (IH, d), 4.32 – 4.43 (2H, m), 4.53 (IH, dd), 5.15 (IH, d), 6.31 (IH, d), 7.21 (2H, dd), 7.34 (IH, d), 7.68 (IH, t), 8.21 (IH, s), 8.53 (IH, s), 9.72 (IH, s). m/z (ES+), [M+H]+ = 464

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 1192-21-8.

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. 27258-33-9, name is 1-Methyl-1H-pyrazole-5-carbaldehyde, A new synthetic method of this compound is introduced below., Formula: C5H6N2O

To a solution of triethyl phosphonoacetate (26.9 g) in tetrahydrofuran (200 ml) was added sodium hydride (60% dispersion in mineral oil, 4.8 G) by portions under ice- cooling. The mixture was stirred at the same temperature for 1 hour. To the reaction mixture was added 1-METHYL-LH-PYRAZOLE- 5-carbaldehyde (33.0 g) in tetrahydrofuran (165 ml) at room temperature, and the mixture was stirred at the same temperature for 1.5 hours. To the resulting solution was added 10% aqueous potassium hydrogen sulfate solution. The mixture was extracted with ethyl acetate twice. The combined organic layers were washed with saturated sodium hydrogen carbonate solution and brine. The extract was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to give ethyl (2E)-3-(1-METHYL-LH-PYRAZOL-5-YL)-2-PROPENOATE (33.4 g) as an oil. IR (neat) 2981,2943, 1713,1703, 1180,781 CM~1. H-NMR (DMSO-d6) 8 1. 26 (3H, t, J = 7.1 Hz), 3.88 (3H, s), 4.20 (2H, q, JAZZ 7.1 Hz), 6.54 (1H, d, J = 15.8 Hz), 6.88 (1H, d, J = 1.8 Hz), 7.45 (1H, d, J = 1.8 Hz), 7.60 (1H, d, J = 15.8 Hz). MS (APCI) 181 (M+H+).

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 of 31108-57-3, 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. 31108-57-3, name is 1H-Pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Compound D (140 mg, 0.27 mmol) was dissolved in DMF (5 ml), then sodium carbonate (50 mg, 0.54 mmol), 1H-pyrazole-4-carbonitrile (57 mg, 0.54 mmol) was added, and the reaction was carried out at 25 C for 4 hours. . Pour into 1N NaOH aqueous solution (20 ml), extract EA four times (30ml x 4), wash twice with 1N hydrochloric acid (30ml x 2), Dry over anhydrous sodium sulfate, After concentration, silica gel column chromatography gave 30 mg of a colorless oily viscous liquid 2-1. The yield was 26%.

The chemical industry reduces the impact on the environment during synthesis 1H-Pyrazole-4-carbonitrile. I believe this compound will play a more active role in future production and life.