Category: 3994-50-1

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

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. 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 3994-50-1

To tert-butyl N-[( iS)- 1 -(3 -bromo-5 -fluorophenyl)but-3 -en-i -yl] carbamate (0.19 g, 0.552 mmol), i-methyl-4-nitro-iH-pyrazole (0.070 g, 0.552 mmol), di(adamantan-i20 yl)(butyl)phosphine (0.059 g, 0.166 mmol), pivalic acid (0.019 ml, 0.166 mmol), K2C03(0.229 g, 1.656 mmol) was added DMF (1.1 ml), and the mixture was purged with Ar. Pd(OAc)2 (0.025 g, 0.110 mmol) was added and the reaction was heated at 120 C for 18 h. The reaction was partitioned between water (15 ml) and EtOAc (30 ml). The aqueous layer was extracted with EtOAc (2 x 20 ml). The combined organic layers was washedwith brine (15 ml), dried over MgSO4, filtered and concentrated. The residue was purified by normal phase chromatography using hexanes and EtOAc as eluents to give tert-butyl N- [(15)-i -[3 -fluoro-5 -(1 -methyl-4-nitro- iH-pyrazol-5 -yl)phenyl]but-3 -en-i -yl]carbamate (0.123 g, 57%) as a yellow oil. ?HNMR(400MHz, CDC13)oe 8.23- 8.i7(m, iH), 7.22-7.16 (m, 1H), 7.10 (s, 1H), 7.01 (dt,J=8.5, 1.9 Hz, 1H), 5.76-5.60 (m, 1H), 5.22-5.11(m, 2H), 4.90 (br. s., 1H), 4.78 (br. s., 1H), 3.78 – 3.69 (m, 3H), 2.60 – 2.48 (m, 2H), 1.41(br. s., 9H).

According to the analysis of related databases, 3994-50-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; CORTE, James R.; DE LUCCA, Indawati; FANG, Tianan; YANG, Wu; WANG, Yufeng; DILGER, Andrew K.; PABBISETTY, Kumar Balashanmuga; EWING, William R.; ZHU, Yeheng; WEXLER, Ruth R.; PINTO, Donald J. P.; ORWAT, Michael J.; SMITH, Leon M. II; WO2015/116886; (2015); 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. 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., Quality Control of 1-Methyl-4-nitro-1H-pyrazole

Example 1 5-chloro-1-methyl-4-nitro-1H-pyrazole [0177] 4-nitro-1-H-pyrazole (5 g, 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 CH2Cl2 (2×150 mL). The organic layer was separated and the solvent was distilled off to yield 1-methyl-4-nitro-1H-pyrazole as a white solid (4.30 g, 76%). [0179] Following WO 2007/99326, to a 500 mL 3-neck-round bottom flask was added 1-methyl-4-nitro-1H-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 NH4Cl (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 Na2SO4 and the organic solvent was distilled off. The crude product was purified via flash chromatography (CH2Cl2/7% MeOH) to yield 5-chloro-1-methyl-4-nitro-1H-pyrazole as a white solid (1.40 g, 20%). 1H NMR (400 MHz, CDCl3) delta 8.13 (s, 1H), 3.92 (s, 3H); ESIMS m/z=162.0 (M+1)

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

Reference:
Patent; GENENTECH, INC.; Hodges, Alastair James; Matteucci, Mizio; Sharpe, Andrew; Sun, Minghua; Wang, Xiaojing; Tsui, Vickie H.; US2013/79321; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 3994-50-1, The chemical industry reduces the impact on the environment during synthesis 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, I believe this compound will play a more active role in future production and life.

A mixture of a portion (0.7 g) of the material so obtained, platinum oxide (0.05 g), ethyl acetate (5 ml) and ethanol (15 ml) was stirred under 3 atmospheres pressure of hydrogen for 2 hours. The catalyst was removed by filtration and the filtrate was evaporated. There was thus obtained the required starting material (0.6 g); 1H NMR Spectrum: (DMSOd6) 3.64 (s, 3H), 6.86 (s, IH), 6.97 (s, IH).

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, 1-Methyl-4-nitro-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/113565; (2007); 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. 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H5N3O2

A solution of l-methyl-4-nitro-lH-pyrazole (9.7 g, 76.7 mmol) and 4-pentenal (10 g, 84.4 mmol) in dry THF (250 mL) was cooled to -78 C and stirred under nitrogen. A solution of LiHMDS (1 M in THF, 192 mL, 191.7 mmol) was added dropwise over a period of 3 hr. The reaction mixture was allowed to warm and to -40 C and stirred for 2 hr, quenched by dropwise addition of saturated ammonium chloride solution (100 mL), warmed to room temperature and diluted with EtOAc (200 mL). The organic layer was washed with saturated ammonium chloride solution (50 mL), separated, dried over MgS04 and the solvent removed under reduced pressure. Purification via silica gel chromatography (0-100% EtOAc/DCM) followed by silica gel chromatography (0-100% EtOAc/isohexane) to gave l-(l-methyl-4- nitro-lH-pyrazol-5-yl)pent-4-en-l-ol as a pale yellow oil (5.75 g, 36%). NMR (400 MHz, CDC13) delta 8.06 (s, 1H), 5.85-5.78 (m, 1H), 5.32-5.26 (m, 1H), 5.12-5.04 (m, 2H), 3.98 (s, 3H), 3.45 (d, / = 8.7 Hz, 1H), 2.92-2.09 (m, 3H), 1.90-1.86 (m, 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; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BURCH, Jason; CHEN, Huifen; WANG, Xiaojing; WO2015/140189; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 3994-50-1, 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. 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

At room temperature, pyrazole (0.2 mol) was dissolved in concentrated sulfuric acid (50 mL) and slowly raised to a temperature of 60 CConcentrated nitric acid (9.2 mL) was added and stirring was continued at 60 C for 1.5 hours.After completion of the reaction, the reaction solution was poured into 600 g of ice water, and the resulting white solid was separated by filtration and washed with water.After extraction with ethyl acetate (100 mL x 3), the organic phase was washed successively with 1% sodium bicarbonate solution (100 mL), water (100 mL) and physiological saline (100 mL), dried over anhydrous sodium sulfate and filtered, Finally, the organic phase liquid was rotary evaporated to give a white solid which was combined with the previously obtained white solid to give compound 2a. The resulting compound 2a (12 mmol) was dissolved in DMSO (9 mL)And potassium carbonate (10.9 mmol) was added successively thereto,Methyl iodide (6 mmol),8-hydroxyquinoline (1 mmol),CuI (0.58 mmol). Argon under the conditions of protection, stirMixed and heated to 130 C,After 20 hours of reaction,The reaction solution was poured into an appropriate amount of water,The resulting green solid was separated by filtration.The mother liquor was extracted with ethyl acetate (100 mL x 3). Finally, the organic phase liquid was evaporated to dryness and the resulting crude product was combined with the previously obtained green solid and purified by silica gel column chromatography to obtain Compound 4a. Compound 4a (1 mmol), hydrazine hydrate (0.5 mL) was added to ethanol (1 mL) and palladium on carbon (0.02 g) was added as catalyst.Heated at 80 C and refluxed for 10 minutes. After the completion of the reaction, the resulting mother liquor was subjected to rotary evaporation and drying to obtain Compound 5a. Compound 4a (1 mmol), hydrazine hydrate (0.5 mL) was added to ethanol (1 mL) and palladium on carbon (0.02 g) was added as catalyst.Heated at 80 C and refluxed for 10 minutes. After the completion of the reaction, the resulting mother liquor was subjected to rotary evaporation and drying to obtain Compound 5a. The compound 8a (1 mmol),EDC (1 mmol), HOBt (1 mmol) was added to DMF(3 mL) for 30 min.The compound 5a, DMAP (1 mmol), triethylamine (500 [mu] L) were added to the activated DMFSolution. At room temperature, stir overnight.After completion of the reaction, 100 mL of saturated sodium chloride solution was added to the reaction solution, and the mixture was washed with ethyl acetateEster extraction (200 mL x 3) extraction. Finally, the organic phase liquid was evaporated under vacuum and evaporated to dryness to obtain a crude product, using a silica gel columnSeparation and purification to give the final compound 9a to give a white solid powder in a yield of 86.4%

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

Reference:
Patent; Nanjing University; Zhu Hailiang; Shi Lu; Wang Zefeng; Wang Chenru; (14 pag.)CN107098861; (2017); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 3994-50-1, name is 1-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 3994-50-1, HPLC of Formula: C4H5N3O2

Example 1 7-(Azetidin-l-yl)-3-methyl-l-(l-methyl-5-(4-(trifluoromethyl)phenyl)-lH- pyrazol-4-yl)-lH-pyrazolo[4, -d]pyrimidine (a) 5-Chloro-l-methyl-4-nitro-lH-pyrazole Lithium bis(trimethylsilyl)amide (1.0 M, 65 mL, 65 mmol) in THF is added dropwise into a solution of l-methyl-4-nitro-lH-pyrazole (5.50 g, 43.3 mmol) and hexachloroethane (10.54 g, 44.5 mmol) in methylene chloride (120 mL) at 25 C. The reaction mixture is stirred at 25 C for 60 min, and then quenched with water (1 mL). The mixture is evaperated to dryness. The residue is washed with water (50 mL), sat. NaHCC>3 two times (2×30 mL) and brine (30 mL) successively, and then dried under vacuum to give 6.50 g of product (93% yield). MS (ESI) mJz 162.0 [M+H]+. NMR (500 MHz, CDC ) delta 8.15 (s, 1H), 3.92 (s, 3H).

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

Reference:
Patent; INTRA-CELLULAR THERAPIES, INC.; LI, Peng; ZHENG, Hailin; SNYDER, Gretchen; WENNOGLE, Lawrence P.; HENDRICK, Joseph; (28 pag.)WO2016/90380; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 3994-50-1, name is 1-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 3994-50-1, Recommanded Product: 3994-50-1

A mixture of a portion (0.7 g) of the material so obtained, platinum oxide (0.05 g), ethyl acetate (5 ml) and ethanol (15 ml) was stirred under 3 atmospheres pressure of hydrogen for 2 hours. The catalyst was removed by filtration and the filtrate was evaporated. There was thus obtained the required starting material (0.6 g); 1H NMR: (DMSOd6) 3.64 (s, 3H), 6.86 (s, IH), 6.97 (s, IH).

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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/40520; (2006); 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. 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, A new synthetic method of this compound is introduced below., Recommanded Product: 3994-50-1

Example 25Synthesis of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(1-methyl-1H-pyrazol-4-yl)-6-(4-morpholinyl)-1,3,5-triazin-2-amineThe compound was synthesized according to Method A.A mixture of 0.996 g (8.82 mmol) of 4-nitropyrazole (J. Med. Chem. 2005, 48, 5780-5793) and 1.33 g (10.6 mmol) of dimethyl sulphate in 10 mL of 1 M NaOH was heated at 35 C. for 48 hrs. The reaction mixture was cooled to RT and the precipitate was filtered, washed with water, and dried to give 0.561 g (50% yield) of 1-methyl-4-nitro-1H-pyrazole: 1H NMR (DMSO-d6) delta8.83 (s, 1H), 8.22 (s, 1H), 3.91 (s, 3H).A mixture of 0.144 g (1.14 mmol) 1-methyl-4-nitro-1H-pyrazole, 0.017 g (0.07 mmol) platinum oxide, and ethyl acetate (5 mL) in ethanol (15 mL) was stirred under 2 atmospheres of hydrogen for 14 hrs. The catalyst was removed by filtration through a pad of celite and the solvent was removed to give 0.080 mg (73% yield) of 4-amino-1-methyl-1H-pyrazole as a purple residue, which was used in the next step without further purification: 1H NMR (DMSO-d6) delta6.98 (s, 1H), 6.88 (s, 1H), 3.76 (br s, 2H), 3.65 (s, 3H).A mixture of 0.405 g (4.27 mmol) of 4-amino-1-methylpyrazole and 0.695 g (1.90 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in DMSO (5 mL) was heated at 125 C. for 15 min. The reaction mixture was cooled to room temperature and water was added. The solid was collected by filtration, washed with water, and dried. Chromatography on alumina, eluting with hexanes/EtOAc (1:1) gave a brown powder. Recrystallization from ethanol/CH2Cl2 gave 0.145 g (18% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(1-methyl-1H-pyrazol-4-yl)-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 225-226 C.; 1H NMR (DMSO-d6) (rotamers) delta10.00 (s, 1H), 9.73 (s, 0.2H), 8.60 (d, J=8.0 Hz, 1H), 8.29 (d, J=7.6 Hz, 0.2H), 7.92 (t, JHF=52.8 Hz, 1H), 7.86-7.80 (m, 2.6H), 7.68 (t, JHF=52.6 Hz, 0.2H), 7.59 (s, 1H), 7.52-7.42 (m, 2.9H), 3.85-3.82 (m, 8.4H), 3.75-3.73 (m, 4.8H); Anal. Calcd. for C19H19F2N9O 0.06EtOAc 0.24H2O: C, 52.9; H, 4.6; N, 28.8. Found: C, 52.9; H, 4.5; N, 28.6%.

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; Pathway Therapeutics Limited; US2011/9405; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 3994-50-1, name is 1-Methyl-4-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. Recommanded Product: 3994-50-1

To a solution of tert-butyl N- [(15)-i -(5 -bromopyridin-3 -yl)but-3 -en- l-yl]carbamate (1.0 g, 3.06 mmol), prepared as described in Intermediate 26, in dioxane (10ml) was added 1-methyl-4-nitro-1H-pyrazole (0.427 g, 3.36 mmol), di(adamantan-1-yl)(butyl)phosphine (0.164 g, 0.458 mmol), K2C03 (1.267 g, 9.17 mmol) and pivalic acid(0.106 ml, 0.917 mmol). The reaction mixture was purged with Ar. Pd(OAc)2 (0.069 g,0.306 mmol) was added and the solution was stirred at 100 C. After 4 h, the reactionwas quenched with water (20 ml) and extracted with EtOAc (3 x 50 ml). The combinedorganic layers were washed with brine (20 ml), dried (MgSO4), filtered, and concentrated.The residue was purified by normal phase chromatography using heptanes and EtOAc aseluents to give tert-butyl N-[( 15)-i -[5 -(1 -methyl-4-nitro- 1 H-pyrazol-5 -yl)pyridin-3 -yl]but-3-en-i-yl]carbamate (0.85 g, 74%) as a white foam. MS(ESI) m/z: 374.5 (M+H).?H NMR (500MHz, CDC13) oe 8.74 (d, J=i .9 Hz, 1H), 8.57 (d, J=i .9 Hz, 1H), 8.25 (s,1H), 7.72 (t, J=i.9 Hz, 1H), 5.73 (ddt, J=17.i, 10.2, 7.2 Hz, 1H), 5.26 – 5.17 (m, 2H),4.99 (br. s., 1H), 4.93 – 4.84 (m, 1H), 3.80 (s, 3H), 2.75 – 2.52 (m, 2H), 1.43 (br. s., 9H).

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