Category: pyrazoles-derivatives

Application of 2075-46-9, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 2075-46-9 name is 4-Nitro-1H-pyrazole, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To a 500 mL round bottom flask containing 4-nitro-i-H-pyrazole (5g, 44.2 mmol) was added sodium hydroxide (1M, 200 mL) and dimethyl sulfate (31 mL, 330 mmol). The mixture was stirred at room temperature for 72 h and the mixture was extracted with CH2C12 (2 x 150 mL). The organic layer was separated and the solvent was distilled off to yield 1- methyl-4-nitro- lH-pyrazole as a white solid (4.30 g, 76%). Following WO 2007/99326, to a 500 mL 3-neck-round bottom flask was added 1- methyl-4-nitro- lH-pyrazole (4.30 g, 33.8 mmol) and THF (12 mL). The mixture was cooled to -78 C and lithium hexamethyldisilazide in THF (1M, 88.4 mL, 90 mmol) was added dropwise via an addition funnel over 20 min. The brown mixture was stirred for 30 min and warmed to -45 C over 30 min. The mixture was cooled back down to -78 C and hexachloroethane (10.5 g, 44.2 mmol) dissolved in THF (20 mL) was added via an addition funnel over 15 min. The mixture was stirred for 2.5 h, warmed from -78 C to -40 C and the reaction was monitored by LCMS. Upon completion of the reaction, the reaction was quenched with a solution of saturated NH4C1 (150 mL), and ethyl acetate (100 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layer was washed with water (150 mL), dried over Na2S04 and the organic solvent was distilled off. The crude product was purified via flash chromatography (CH2C12/ 7% MeOH) to yield 5-chloro-l-methyl-4-nitro- lH-pyrazole as a white solid (1.40 g, 20%). 1H NMR (400 MHz, CDC13) delta 8.13 (s, 1H), 3.92 (s, 3H); ESIMS m/z = 162.0 (M+l)

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BURCH, Jason; CHEN, Huifen; WANG, Xiaojing; WO2015/140189; (2015); 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. 1613191-73-3, name is Allyl 3,5-diamino-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H10N4O2

[0456] 1,1,3,3-tetramethoxypropane 35a (20 g, 121.8mmol) was dissolved in water (200 ml). p-Toluenesulphonicacid monohydrate (23.17 g, 121.8 mmol) was added and themixture stirred at 19-20 C. for 90 minutes. 1-(Chloromethyl)-4-fluoro-1 ,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate37 (Selectfluor, 1.4 eqv, 60.4 g, 170.5 mmol)was added portionwise. The addition was endothermic (20.1 oC. to 19.4 C.) however the temperature began to rise slowlyonce the addition was complete (temp increased to 25.4 C.over 45 minutes). The selectfluor dissolved over 1 hr. Themixture was allowed to stir at ambient temperature for 18 hrs.The mixture was homogeneous after this time. DMSO (150ml) was added slowly over 5 minutes. The addition wasexothermic-the temperature increased from 20.4 C. to34.2 C. during the addition. The mixture then began to cool.The resulting mixture was stirred for 45 minutes. Compound3 (21.4 g, 115.7 mmol) was then added portionwise. Theaddition was not exothermic. The mixture was heated to 85C. for 4 hrs (Lc/Ms profile was identical at 2 hr and 4 hr timepoints). The stirred mixture was then allowed to cool to ambienttemperature overnight. The resulting reaction mixturewas a slurry. Water (150 ml) was added slowly to the resultingslurry. The temperature increased from 20.4 C. to 21.5 C.The slurry was stirred for 2 hrs, and then the product wasisolated by filtration. The cake was washed with water anddried on the sinter to a beige solid (15.5 g). The product wasfurther dried in a vac oven at 40 C. for 20 hrs. This gavecompound 4a as a beige solid (13.5 g, 50% yield). HPLCpurity 97.7% area; 1H NMR (500 MHz, DMSO-d6) o 4.83(2H, d), 5.29 (lH, d), 5.49 (lH, d), 6.04-6.14 (lH, m), 6.57(2H, brs), 8.80 (lH, m), 9.40 (lH, m); 19F NMR (500 MHz,DMSO-d6) o -153.1.

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 1613191-73-3.

Reference:
Patent; Charrier, Jean-Damien; Davis, Christopher John; Fraysse, Damien; Etxebarria I Jardi, Gorka; Pegg, Simon; Pierard, Francoise; Pinder, Joanne; Studley, John; Zwicker, Carl; Sanghvi, Tapan; Waldo, Michael; Medek, Ales; Shaw, David Matthew; Panesar, Maninder; Zhang, Yuegang; Alem, Naziha; US2015/158872; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 54605-72-0, name is 1-Phenylpyrazole-4-carboxaldehyde, 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 C10H8N2O

A mixture of 1-phenylpyrazole-4-carbaldehyde (18.5 mg, 0.11 mmol), paracyclophanyl piperazine (31.4 mg, 0.11 mmol) and sodium triacetoxyborohydride (27.5 mg, 0.13 mmol) in dichloromethane (1.5 mL) was stirred at room temperature for 24 h. Then, the mixture was added to a saturated aqueous solution of NaHCO3 and extracted with dichloromethane. The organic layer was dried (Na2SO4) and evaporated and the residue was purified by flash chromatography (petroleum ether/ethyl acetate 4:6) to give pure 4 (35.2 mg, 72%) as a colorless solid (mp 78 C). EI-MS: m/z 448 (M+); 1H NMR: (CDCl3, 360 MHz) delta (ppm): 2.60-2.81 (m, 5H), 2.85-3.12 (m, 9H), 3.25 (ddd, J = 12.3 Hz, 9.0 Hz, 6.0 Hz, 1H), 3.37 (ddd, J = 12.7 Hz, 9.7 Hz, 2.4 Hz, 1H), 3.60 (s, 2H), 5.71 (d, J = 1.8 Hz, 1H), 6.27 (dd, J = 7.8 Hz, 1.8 Hz, 1H), 6.35 (dd, J = 7.9 Hz, 1.9 Hz, 1H), 6.40 (d, J = 7.8 Hz, 1H), 6.44 (dd, J = 7.9 Hz, 1.9 Hz, 1H), 6.52 (dd, J = 7.9 Hz, 1.9 Hz, 1H), 6.69 (dd, J = 7.9 Hz, 1.9 Hz, 1H), 7.24-7.31 (m, 1H), 7.41-7.48 (m, 2H), 7.67-7.73 (m, 3H), 7.92 (s, 1H); IR: (KBr) nu (cm-1): 1596. Anal. Calcd for C30H32N4: C, 80.32; H, 7.19; N, 12.49. Found: C, 80.63; H, 7.13; N, 12.32.

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

Reference:
Article; Sanna, Fabrizio; Ortner, Birgit; Huebner, Harald; Loeber, Stefan; Tschammer, Nuska; Gmeiner, Peter; Bioorganic and Medicinal Chemistry; vol. 21; 7; (2013); p. 1680 – 1684;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 71229-85-1, name is 4-Bromo-1-ethyl-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. name: 4-Bromo-1-ethyl-1H-pyrazole

To a stirred solution of 6-chloro-7-fluoro-1H-indole 8 (400 mg, 2.36 mmol) in toluene (10 mL) were added 4-bromo-1-ethyl-1H-pyrazole 4 (Step 3 above; 414 mg, 2.36 mmol), potassium phosphate (1.25 g, 5.91 mmol), N,N?-dimethylethylenediamine (84 mg, 0.95 mmol) and Cu(I)I (45 mg, 0.24 mmol) at RT under inert atmosphere. The resulted solution was purged with argon and sealed the tube. The reaction mixture was then heated to 140 C for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to RT, dilutedwith hexane (10 mL) and filtered through a short pad of celite. The filtrate was washed with water (2×10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel chromatography; 8-10% EtOAc/Hexanes) to afford compound 9 (224 mg, 36%) as a light brown thick liquid. ?H NMR (500 MHz, CDC13): oe 7.64 (s, 1H), 7.61 (s, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7. 12-7.07 (m, 2H), 6.60-6.59 (m, 1H), 4.22 (q, J = 7.5 Hz, 2H), 1.55 (t, J = 7.5 Hz, 3H); LC-MS (ES): 94.7%; m/z 264.1 (M + H); (column: X Select C-18, 50 x 3.0 mm, 3.5 gm); RT 3.87 mm; 5 mMNFI4OAc: ACN; 0.8 mL/min).

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

Reference:
Patent; PHARMAKEA, INC.; BAIN, Gretchen; EVANS, Jillian Frances; HUTCHINSON, John Howard; LONERGAN, David; (123 pag.)WO2016/191427; (2016); A1;,
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. 449758-17-2, name is 1-(2-Tetrahydropyranyl)-1H-pyrazole, A new synthetic method of this compound is introduced below., Quality Control of 1-(2-Tetrahydropyranyl)-1H-pyrazole

Step 1: 5-(4-(Benzyloxy)benzyl)-l-(tetrahydro-2H-pyran-2-yl)-lH-pyrazole l-(Tetrahydro-2H-pyran-2-yl)- lH-pyrazole (6.00 g, 39.4 mmol) in THF (180 mL) was cooled to about – 78 C. n-Butyllithium (1.6 M in hexane) (27.1 mL, 43.4 mmol) was added dropwise over about 1 li. The reaction was stirred at about -78 C for about 1 h. l~(Benzyloxy)-4~(bromomethyl)benzene (12.0 g, 43.4 mmol) (prepared in a similar fashion to Preparation 3, step 2 from (4-(benzyloxy)plienyl)methanol) was added and the reaction was allowed to warm to about -50 C. The mixture was diluted with sat. aq. NaHC03 (75 mL) and water (50 mL). The aqueous layer was extracted with DCM (3 x 50 mL). The combined organic layers were dried over MgS04 , filtered, and concentrated. The residue was purified on silica gel (5-20% EtOAc/heptane) to give the title product (10.2 g, 74.3%); LC/MS (Table A, Method j) Rt = 1.77 min; MS m/z: 347 (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:
Patent; ABBVIE INC.; ARGIRIADI, Maria; BREINLINGER, Eric; DIETRICH, Justin, D.; FRIEDMAN, Michael; IHLE, David; MORYTKO, Michael; MULLEN, Kelly; OSUMA, Augustine; LO SCHIAVO, Gloria, Y.; WILSON, Noel, S.; (303 pag.)WO2016/168633; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 133228-21-4, name is N,N-Dimethyl-1H-pyrazole-1-sulfonamide, 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 133228-21-4, Formula: C5H9N3O2S

Step A: Preparation of3-Bromo-N,N-dimethyl- 1 H-pyrazole- 1-sulfonamide To a solution of N-dimethylsulfamoylpyrazole (44.0 g,0.25 1 mol) in dry tetrahydrofuran (500 mE) at 78 C. wasadded dropwise a solution of n-butyllithium (2.5 M inhexane,105.5 mE, 0.264 mol) while maintaining the temperaturebelow 60 C. A thick solid formed during the addition. Uponcompletion of the addition the reaction mixture was maintained for an additional 15 minutes, afier which time a solution of 1 ,2-dibromotetrachloroethane (90 g, 0.276 mol) intetrahydroffiran (150 mE) was added dropwise while maintaining the temperature below .-70 C. The reaction mixtureturned a clear orange; stirring was continued for an additional15 minutes. The 78 C. bath was removed and the reactionwas quenched with water (600 mE). The reaction mixture wasextracted with methylene chloride (4x), and the organicextracts were dried over magnesium sulfate and concentrated.The crude product was further purified by chromatography onsilica gel using methylene chloride/hexane (50:50) as eluentto afford the title product as a clear colorless oil (57.04 g).?H NMR (CDC13) oe 3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m,1H).

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

Reference:
Patent; E I DU PONT DE NEMOURS AND COMPANY; Berger, Richard Alan; Annan, Isaac Billy; Lahm, George Philip; Flexner, John Lindsey; Selby, Thomas Paul; Stevenson, Thomas Martin; US9173400; (2015); B2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 3920-50-1, A common heterocyclic compound, 3920-50-1, name is Pyrazole-3-carboxaldehyde, molecular formula is C4H4N2O, 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 flask was charged with CuI (79 mg, 0.42 mmol), 8-hydroxyquinoline-N-oxide (134 mg, 0.83 mmol), Cs2CO3 (2.713 g, 8.33 mmol), 1H-pyrazole-3-carbaldehyde 42 (400 mg, 4.16 mmol). The flask was evacuated and backfilled with argon. Iodobenzene (0.70 mL, 6.24 mmol) and DMSO (5 mL) were added to the flask under argon atmosphere. After stirring at 90 C for 48 h, the mixture was diluted with water, and extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with brine, dried with Na2SO4, filtered, concentrated and purified by silica gel chromatography to afford 68b as a pale yellow solid (329 mg, 46 %).

The synthetic route of 3920-50-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yao, Yiwu; Liao, Chenzhong; Li, Zheng; Wang, Zhen; Sun, Qiao; Liu, Chunping; Yang, Yang; Tu, Zhengchao; Jiang, Sheng; European Journal of Medicinal Chemistry; vol. 86; (2014); p. 639 – 652;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 82560-12-1,Some common heterocyclic compound, 82560-12-1, name is 3-Amino-5-tert-butylpyrazole, molecular formula is C7H13N3, 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.

d. 4-[5-(5-Amino-3-tert-butyl-pyrazol-1-yl)-2-chloro-phenoxy]-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester (Intermediate Vd) A microwave vial was charged with 3-tert butyl-1H-pyrazole-5-amine (1.03 g, 7.39 mmol), copper (I) iodide (70.3 mg, 0.37 mmol) and potassium carbonate (2.14 g, 15.5 mmol) and the vial sealed with a septum, evacuated and purged with argon. Trans-N,N’-dimethylcyclohexane-1,2-diamine (210 mg, 1.48 mmol) was then added, then a solution of Intermediate Vc (4.26 g, 8.86 mmol) in toluene (7.5 mL, degassed with argon) was added, and the reaction was subjected to microwave irradiation (150 C. for 1 h). The reaction mixture was then filtered through Celite, and the filtrate concentrated in vacuo. Purification by FCC, eluting with 0-60% EtOAc/cyclohexane, to afford the title compound (2.41 g, 66%). LCMS (Method 3) Rt 4.68 min, m/z 493, 495 [MH+].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Amino-5-tert-butylpyrazole, its application will become more common.

Reference:
Patent; CHIESI FARMACEUTICI S.p.A.; Alcaraz, Lilian; Hurley, Christopher; Cridland, Andrew Peter; Jennings, Andrew Stephen Robert; US2014/364412; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

26621-44-3, name is 3-Nitro-1H-pyrazole, belongs to pyrazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 3-Nitro-1H-pyrazole

To a stirred mixture of 3-nitro-lH-pyrazole (3.16 g, 27.9 mmol) in glacial acetic acid (20 mL) at 0 C was added fuming nitric acid (2.6 mL, 58.69 mmol) dropwise, followed by acetic anhydride (6.6 niL, 69.87 mmol). The mixture was stirred and allowed to warm to rt over 3 h, then poured into ice water (50 mL) and stirred for 20 h. The mixture was extracted with EtOAc combined organic layers were dried over MgS04, filtered and concentrated to dryness to afford 1,3-dinitro-lH- pyrazole (4.3 g, 97%). H NMR (300 MHz, DMSO- 6) delta 8.00 (br s, 1H), 6.44 (br s, 1H).

The synthetic route of 26621-44-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMBIT BIOSCIENCES CORPORATION; CHAO, Qi; HADD, Michael, J.; HOLLADAY, Mark, W.; ROWBOTTOM, Martin; WO2012/30924; (2012); A1;,
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. 35277-02-2, name is 4-Fluoro-1H-pyrazole, A new synthetic method of this compound is introduced below., Formula: C3H3FN2

2-Chloro-N-[(dimethylamino)methylene]-5-[(diphenylmethylene)amino]pyridine-3-sulfon- amide (1.00 g, 2.34 mmol) was dissolved in DMSO (18 mL). 4-Fluoro-1H-pyrazole (403mg, 4.69 mmol), potassium iodide (389 mg, 2.34 mmol) and potassium phosphate (746 mg, 3.51 mmol) were added and the reaction mixture was stirred overnight at 100CC. Afterwards it was concentrated in vacuo, extracted with dichloromethane/water and the organic phase was washed with brine and dried over sodium sulfate followed by concentration in vacuo.Due to partial deprotection, the material was redissolved in dimethylformamide (2 mL) and stirred overnight with 1 ,1-dimethoxy-N,N-dimethylmethanamine (0.5 mL). The reaction mixture was concentrated in vacuo, extracted with dichloromethane/water and the organic phase was washed with brine and dried over sodium sulfate followed by concentration invacuo to give crude N-[(dimethylamino)methylene]-5-[(diphenylmethylene)amino]-2-(4-fluoro-1 H-pyrazol-1 -yl)pyridine-3-sulfonamide (723 mg).LC-MS (Method A): Rt = 1.25 mm, MS (ESIpos): m/z = 477 [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:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; WERNER, Stefan; MESCH, Stefanie; CLEVE, Arwed; BRAeUER, Nico; HERBERT, Simon, Anthony; KOCH, Markus; DAHLLOeF, Henrik; OSMERS, Maren; HARDAKER, Elizabeth; LISHCHYNSKYI, Anton; (673 pag.)WO2017/191000; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics