Tag: M.W:100-200

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. 133228-21-4, name is N,N-Dimethyl-1H-pyrazole-1-sulfonamide, A new synthetic method of this compound is introduced below., COA of Formula: C5H9N3O2S

Step A: Preparation of3-Chloro-N,N-dimethyl- 1 H-pyrazole- 1-sulfonamideTo a solution of N-dimethylsulfamoylpyrazole (188.0 g,1.07 mol) in dry tetrahydrofuran (1500 mE) at 78 C. wasadded dropwise a solution of 2.5 M n-butyllithium (472 mE,1.18 mol) in hexane while maintaining the temperature below65 C. Upon completion of the addition the reaction mixturewas maintained at 78 C. for an additional 45 minutes, afterwhich time a solution of hexachloroethane (279 g, 1.18 mol)in tetrahydrofuran (120 mE) was added dropwise. The reac40 tion mixture was maintained for an hour at 78 C., warmedto 20 C. and then quenched with water (1 E). The reactionmixture was extracted with methylene chloride (4×500 mE);the organic extracts were dried over magnesium sulfate andconcentrated. The crude product was further purified by chro45 matography on silica gel using methylene chloride as eluentto afford the title product compound as a yellow oil (160 g).?HNMR(CDC13) oe 3.07 (d, 6H), 6.33 (s, 1H), 7.61 (s, 1H).

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; 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

Adding a certain compound to certain chemical reactions, such as: 5334-39-4, name is 3-Methyl-4-nitro-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 5334-39-4, COA of Formula: C4H5N3O2

To a solution of cw-3-benzyloxycyclobutanol (17 g, 95 ,4 mmol) and 3-methyl-4-nitro-lH-pyrazole (12.1 g, 95.4 mmol) in THF (350 mL) was added PPh3 (37.5 g, 143 mmol). Then, DIAD (28.9 g, 143 mmol) was added slowly at 0 C, and the mixture was stirred at 15 C for 20 h. The mixture was quenched with H2Q (100 mL), then filtered. The filtrate was then extracted with EtOAc (3 x 70 mL), The organic phase was washed with brine (30 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel colum chromatography (PE:EtOAc = 10: 1 to 7: 1), to give trans- l-(3-benzyloxycyclobutyl)-5-methyl-4-nitro-pyrazole and trans-l-(3- benzyloxycyclobutyl)-3-methyl-4-nitro-pyrazoleTo a solution of /ra>v-l-(3-benzyloxycyclobutyl)-5-methyl-4-nitro-pyrazole and rra?is-l-(3-benzyloxyxyck)butyl)-3-methyl-4-nitro-pyrazole (19.5 g, 67.9 mmol) in DCM (200 mL) was added BC1 (1 M, 26.5 mL) at 0 C, and the mixture was stirred at 0 C for 2 h. The mixture was poured into water (200 mL) slowly, then extracted with DCM (2 x 100 mL). The organic phase was washed with aqueous ai K ()·. (50 mL), brine (40 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography (PE/EtOAc = 2 : 1 to 1 : 1), to give trans-3-[5- methyi-4-nitro-pyrazol- 1 -yl]cyclobutanol and trans-3-[3-methyl-4-nitro-pyrazol-1-yl]cyclobutanol as a mixture as a white soli d . To a mixture of trans-3~[5-methyl-4-nitro- pyrazol- 1 -yl] cyclobutanol and rrav-3-[3-methyl-4-nitro-pyrazol-l-yl]cyclobutanol ( 1.4 g, 7.1 mmol) in CL CN (100 mL) was added Cul (541 mg, 2.84 mmol) and 2,2-difluoro-2-fluorosulfonyl-acetic acid ( 1.9 g, 10.65 mmol) at 15 C, and the mixture was stirred at 55 C for 2 h. The mixture was quenched with water (5 mL), The solvent was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE: EtOAc = 10: 1), to give trans- 1 – [3 -(difluoromethoxy)cyciobutyl] -5 -methy 1-4-nitr o-pyrazole and trans- 1-[3- (difluoroinethoxy)cyclobutyi]~3-methyl-4-nitro~pyrazole as a yellow solid To a mixture of ras-l-[3- (difiuoi methoxy)cyclobutyl |-5~methyl-4″nitro-pyrazoie and ro;/s~l~[3-(difluoromethoxy)cyclobutyl]-3- methyl-4-nitro-pyrazole (350 mg, 1.42 mmol) and NH4CI (379 mg, 7.08 mmol) in EtOH (8,8 mL) and H20 (2.2 mL) was added powder Fe (395 mg, 7.08 mmol) at 15 C, then the mixture was stirred at 80 C for 2 h. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The mixture was extracted with EtOAc (2 x 30 mL). The organic phase was washed with brine (10 mL), dried over anhydrous Na2S04, filtered and concentrated to give trans-l-[3- (dif]uoromethoxy)cyclobutyl]-5-methyl-pyrazol-4-amine and rranA”-l-[3-(di£luoromethox’)cyclobutyl]-3- methyl-pyrazol-4-amme as a brown oil. LCMS: RT 2.06 min, m/z ==393.1 |M+H]+. To a mixture of trans- 1 – f 3 -(difluoromethoxy )cyclobutyl] -5 -methyl -pyrazol -4-amine and trans- 1 – f 3 – (difluoromethoxy)cyclobutyl]-3-methyl-pyrazol-4-amine (270 mg, 1.24 mmol) in 1,4-dioxane (10 mL) was added 2~chloro-N-methy3-5~(trifliJoromethyi)pyrimidin-4-amine (262 mg, 1.24 mmol) and TsOH-H20 (236 mg, 1.24 mmol) at 15 C. The mixture was warmed to 90 C and stirred for 2 h. The reaction was quenched with H20 ( 1 mL), then concentrated under reduced pressure. The crude was purified by prep-HPLC (FA) to give trans-N2-[l-[3-(difluoromethoxy)cyclobutyl]-5-methyl-pyrazol-4-yl]-N4-methyl-5- (trifluoromethyl)pyrimidine-2,4-diamine (D-25): 1H NMR (400 MHz, CDC13): delta rhorhoiotaeta 8.08 (s, 1 H) 7.71 – 7.98 (br. s., 1 H), 6.23 (t, J =3.2 Hz, 1 H), 5 ,20 (t, .7 =3,2 Hz, 1 H), 4.1 (t, J =3.2 Hz, 1 H), 4 ,75 (br. s., 1 H), 3,03 (s, 3 H), 2.97 – 3.03 (m, 2 H), 2.68 – 2,73 (m, 2 H), 2,20 (s, 3 H); HPLC: RT 2.06 mm; MS: m/z: 393.1 [M+H]+ trans-N2-[l-[3-(difluoromethoxy)cyclobutyl]-3-methyl-pyrazol-4-yl]-]N4-methyl-5- (trifluoromethyl)pyrimidine-2,4-diamine (D-26): ‘H NMR (400 MHz, CDCi3): delta rhorhoetaiota 8.21 (s, 1 H), 8.07 (br, s,, 1 ). 7.89 (s, 1 H), 6,22 (t, J =3 ,2 Hz, I H), 5.34 (br. s., 1 H), 4.96-5.02 (m, 1 H), 4,81 – 4.90 (m, 1 H) 3.04 – 3.15 (m, 3 H), 2.84 – 2.96 (m, 2 H), 2.65 – 2.78 (m, 2 H), 2.31 (s, 3 H); HPLC: RT 2.06 min; MS: m/z: 393.1 j M 1 1 ] –

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; DENALI THERAPEUTICS INC.; ESTRADA, Anthony A.; FENG, Jianwen A.; LYSSIKATOS, Joseph P.; SWEENEY, Zachary K.; DE VICENTE FIDALGO, Javier; (271 pag.)WO2017/87905; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

89181-79-3, name is 3-Amino-1-methyl-1H-pyrazole-4-carboxamide, 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. Application In Synthesis of 3-Amino-1-methyl-1H-pyrazole-4-carboxamide

General procedure: To a solution of carboxamides 11-14 (0.015 mol) in dry acetone(10 mL), benzoyl isothiocyante (0.0165 mol, 1.1 equiv) was addedand refluxed at 60 C for 12 h. The reaction mixture was cooled.The resulting yellow solid was filtered, washed with acetone and dried under vacuum. The crude product was further recrystalizedfrom methanol to obtain a pure solids.

The synthetic route of 89181-79-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Venkatesan, Gopalakrishnan; Paira, Priyankar; Cheong, Siew Lee; Vamsikrishna, Kosaraju; Federico, Stephanie; Klotz, Karl-Norbert; Spalluto, Giampiero; Pastorin, Giorgia; Bioorganic and Medicinal Chemistry; vol. 22; 5; (2014); p. 1751 – 1765;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 29097-00-5, 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. 29097-00-5, name is Methyl 3-amino-1H-pyrazole-4-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

a) A mixture of 11.5 g of methyl 5-aminopyrazole-4-carboxylate, 16 ml of ethyl omega, omega, omega-trifluoroacetoacetate and 150 g of polyphosphoric acid was heated to 100 while stirring for 16 hours. After cooling to 20, cold water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with 1N aqueous hydrochloric acid and aqueous saturated sodium chloride solution and then dried over Na2 SO4. The solvent was evaporated in a vacuum and the residue was taken up in ether. The solid product was filtered off under suction and recrystallized from 2-propanol. There was obtained an isomer of the product, namely methyl 7-hydroxy-5-(trifluoromethyl)pyrazolo-[1,5-a]pyrimidine-3-carboxylate of m.p. 216-217. The product enriched in the mother liquors was crystallized from ethyl acetate. There was obtained methyl 5-hydroxy-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate of m.p. 149-150.

The synthetic route of Methyl 3-amino-1H-pyrazole-4-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoffmann-La Roche Inc.; US5036064; (1991); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 3994-50-1, A common heterocyclic compound, 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, molecular formula is C4H5N3O2, 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 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)

The synthetic route of 3994-50-1 has been constantly updated, and we look forward to future research findings.

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

Synthetic Route of 5334-39-4, 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. 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows.

A solution of 550 mg (2.45 mmol) 4-[(5-methyl-4-nitro-1 H-pyrazol-1 – yl)methyl]piperidine and 4-[(3-methyl-4-nitro-1 H-pyrazol-1 -yl)methyl]piperidine (intermediate 18B) in 5 mL DMF was stirred with 195 muL (2.06 mmol) ethanesulfonyl chloride and 1.23 mL (8.83 mmol) triethylamine overnight. Saturated aqueous sodium bicarbonate was added to the reaction. The mixture was extracted with ethyl acetate, and the combined organic phase was washed with brine, dried, filtered, and evaporated. 628 mg of the desired title compounds as crude product were obtained which were used without further purification. 1 H NMR (400 MHz, DMSO d6): delta (ppm) = 1.19 (t, 3H), 1.20 / 1.27 (m, 2H), 1.57 (m, 2H), 2.00 (m, 1 H), 2.42 / 2.62 (s, 3H), 2.76 (m, 2H), 3.01 (q, 2H), 3.58 (m, 2H), 4.03 / 4.09 (d, 2H), 8.80 / 8.24 (s, 1 H).

The chemical industry reduces the impact on the environment during synthesis 3-Methyl-4-nitro-1H-pyrazole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BUCHMANN, Bernd; HEISLER, Iring; MUeLLER, Thomas; CLEVE, Arwed; HEROULT, Melanie; NEUHAUS, Roland; PETRUL, Heike; QUANZ-SCHOeFFEL, Maria; (194 pag.)WO2016/12474; (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. 16461-94-2, name is 4-Bromo-1H-pyrazol-3-amine, A new synthetic method of this compound is introduced below., COA of Formula: C3H4BrN3

Experimental steps: Weigh AsB-COOH (67.4 mg, 0.142 mmol, 1 eq) in a 50 ml round bottom flask.The compound was dissolved in 2 ml of anhydrous 1,2-dichloroethane, and then EDC (57.2 mg, 0.298 mmol, 2 eq) was weighed.HoBt (75.2 mg, 0.5565 mmol, 4 eq) was reacted in the reaction mixture for 4 h at room temperature.The reamine (0.3 mmol, 2 eq) was refluxed at 80 C for 12 h, and the reaction was followed by TLC.After the completion of the reaction, the solvent was evaporated under reduced pressure at room temperature, and extracted with 0.5 M HCl and EA (V: V = 1:1) to obtain an organic phase (50 ml of a separating funnel).The obtained organic phase was transferred to a 125 ml separatory funnel, followed by saturated brine (2×20 ml), 5% sodium hydrogen carbonate solution (2×20 ml).Saturated saline solution (3 × 20 ml) was added, and the pH of the saturated saline solution extracted at the end was measured, and the pH was neutral.The organic phase was dried over anhydrous sodium sulfate, and the crude product was evaporated under reduced pressure at 45 C. White soldi, yiled 60.5%

The synthetic route of 16461-94-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; South China Normal University; Long Yuhua; Li Tingmei; She Zhigang; Fan Weilong; Wen Shitong; Yan Zhangyuan; Guo Huixian; Huang Cuiying; Jiang Lasheng; (32 pag.)CN108191944; (2018); 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. 3469-69-0, name is 4-Iodopyrazole, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 3469-69-0

To a solution of 4-iodopyrazole (1.3 g, 6.8 mmol) in dioxane (10 mL) was added iodomethane (0.42 mL, 6.8 mmol) and the resulting mixture stirred at room temperature for 96 h. The mixture was concentrated in vacuo and the residue mixed with methylene chloride and filtered. The filtrate was concentrated in vacuo to provide 1.35 g (95%) of the title compound as a colorless oil. 1H NMR (CDCl3) delta 7.47 (s, 1H), 7.38 (s, 1H), 3.90 (s, 3H).

According to the analysis of related databases, 3469-69-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Eli Lilly and Company; US6797723; (2004); B1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 112029-98-8, 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. 112029-98-8 name is (1-Methyl-1H-pyrazol-4-yl)methanol, 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.

Under a stream of nitrogen, cyanomethylenetributylphosphorane (0.06 mL) was dropped into a 0.2-mL toluene solution of the compound (30 mg) produced in Reference Example 20 and (1-methylpyrazol-4-yl)methanol (9.6 mg), and the mixture was stirred overnight at 100C. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (7 mg) having the following physical property values. 1H-NMR (CDCl3): delta 1.26, 1.39-1.42, 1.68-1.85, 2.28-2.51, 2.55-2.65, 2.83-3.05, 3.87-4.01, 4.04-4.18, 4.89, 6.40, 6.72-6.79, 7.06-7.38, 7.41, 7.51, 8.77, 9.13.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (1-Methyl-1H-pyrazol-4-yl)methanol, and friends who are interested can also refer to it.

Reference:
Patent; Ono Pharmaceutical Co., Ltd.; YOSHIDA, Takao; SHOYAMA, Akiko; TAKANO, Hirotsugu; (103 pag.)EP3482760; (2019); 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 4522-35-4 as follows. Recommanded Product: 4522-35-4

NaH (60% dispersion in mineral oil, 143 mg, 3.57 mmol) was added to a stirred solution of 3-iodo-lH-pyrazole [4522-35-4] (659 mg, 4.00 mmol) in DMF (20 mL) at 0 C under N2 atmosphere. The mixture was stirred at room temperature for 30 min. 2- (Trimethylsilyl)ethoxymethyl chloride [76513-69-4] (0.66 mL, 3.74 mmol) was added at 0 C and the reaction mixture was stirred at room temperature for 16 h. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 10/90). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-188 and 1-189 (965 mg, 86%).; Cul (28.3 mg, 0.15 mmol), N,N?-dimethylcyclo hexane- 1, 2-diamine (46.9 uL, 0.30 mmol) and K2C03 (411 mg, 2.98 mmol) were added to a solution of 1-188 and 1-189 (965 mg, 2.98 mmol) in l,4-dioxane (10 mL) in a sealed tube while nitrogen was bubbling. After 10 min, 4-chloro-lH-pyrrolo[3,2-c]pyridine [60290-21-3] (227 mg, 1.49 mmol) was added. The reaction mixture was stirred at room temperature for 10 min, and at 100 C for 20 h. The mixture was diluted with water and extracted with EtOAc. The combined organic extarcts were dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; EtOAc in heptane, gradient from 0/100 to 15/85). The desired fractions were collected and concentrated in vacuo to afford a mixture of 1-190 and I- 191 (270 mg, 51%).

According to the analysis of related databases, 4522-35-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BARTOLOME-NEBREDA, Jose Manuel; TRABANCO-SUAREZ, Andres, Avelino; TRESADERN, Gary John; MARTINEZ LAMENCA, Carolina; LEENAERTS, Joseph Elisabeth; OEHLRICH, Daniel; BUIJNSTERS, Peter Jacobus Johannes Antonius; VELTER, Adriana, Ingrid; VAN ROOSBROECK, Yves, Emiel, Maria; (171 pag.)WO2019/243535; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics