Tag: M.W:100-200

Synthetic Route of 25016-11-9, 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 25016-11-9 as follows.

To a solution of l-methyl-IH-pyrazole-4-carbaldehyde (104a)(4.8 g, 43.6 mmol) in tetrahydrofuran (80 mL) was cooled to 0 C was added dropwise (3- (bis(trimethylsilyl)amino)phenyl)rnagnesium chloride (49c) (49.0 mL, 49.0 mmol) and stirred at 0 C for 2 h. The reaction was quenched with saturated aqueous NH4CI (1 20 mL)and extracted with ethyl acetate (2 x 120 rnL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4 followed by filtration and concentration. The residue was dissolved in ether (200 mL), treated with 4 N HCI in I ,4-dioxane (24 mL) and stirred at room temperature for 2 h. The solid obtained was collected by filtration washedwith ether, dried under vacuum to give (3-aminophenyl)(l-methyl-IH-pyrazol-4- yl)methanol (104b) (6.01 g, 68%) as an off-white solid; ?H NMR (300 MHz, DMSO-d(,) 8 7.47 (s, 111), 7.46- 7.20 (in, 5H), 5.69 (s, I H), 3.76 (s, 3H); MS (ES+) 204.1 (M+1).

According to the analysis of related databases, 25016-11-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; KOTIAN, Pravin, L.; BABU, Yarlagadda, S.; WU, Minwan; CHINTAREDDY, Venkat, R.; KUMAR, V., Satish; ZHANG, Weihe; WO2015/134998; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 1780-72-9, These common heterocyclic compound, 1780-72-9, name is 4-Bromo-5-methyl-1H-pyrazol-3-amine, 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 kinetics of reactions were followed by measuring the change in absorbance at suitable wavelengthsas a function of time. Working wavelengths were determined for each reaction system, recording thespectra of reaction mixture over wavelength range between 220 and 600 nm. Substitution reactionswere studied under pseudo-first-order conditions whereas the concentration of entering ligand wasalways in large excess (at least 10-fold). Reactions were initiated by mixing equal volumes (1.5 cm3) ofcomplex (2 × 10-4 M) and ligand (2 × 10-3; 4 × 10-3; 6 × 10-3; 8 × 10-3; 1 × 10-2 M) solutions in a quartzcuvette. The changes in absorbance versus time were fitted as a single-exponential function usingOrigin Pro 8. Values for the pseudo-first-order rate constants, kobsd, were calculated as the average valuefrom three to five independent kinetic runs. Experimental data are reported in tables S2-S13 (supplementarymaterial). The values of pseudo-first-order rate constants, kobsd, at 298 K were recalculatedby Guggenheim and Kezdy-Swinbourne methods (table 14S) [33, 34]. All reactions were studied atfour different temperatures (288, 298, 308, and 313 K). The activation parameters, DeltaH? and DeltaS?, werecalculated using the Eyring equation. Eyring plots for all studied systems are given in supplementarymaterial, figures 4S-15S.

Statistics shows that 4-Bromo-5-methyl-1H-pyrazol-3-amine is playing an increasingly important role. we look forward to future research findings about 1780-72-9.

Reference:
Article; Kosovi?, Milica; Jovanovi?, Sne?ana; Bogdanovi?, Goran A.; Giester, Gerald; Ja?imovi?, ?eljko; Bugar?i?, ?ivadin D.; Petrovi?, Biljana; Journal of Coordination Chemistry; vol. 69; 19; (2016); p. 2819 – 2831;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 612511-81-6,Some common heterocyclic compound, 612511-81-6, name is (1-Methyl-1H-pyrazol-3-yl)methanamine, molecular formula is C5H9N3, 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 methyl 4-fluoro-3-nitrobenzoate (350 mg, 1 .758 mmol) in DMF (5 mL) were added (1 – methyl-1 H-pyrazol-3-yl)methanamine (205 mg, 1 .845 mmol) and K2C03 (316 mg, 2.285 mmol), and the reaction mixture was stirred at room temperature overnight. The reaction was then quenched with water (10 mL), and the resulting solid was isolated by filtration, washed with water, and dried in vacuum oven for 4 hours to afford methyl 4-(((1 -methyl-1 H- pyrazol-3-yl)methyl)amino)-3-nitrobenzoate (395 mg) as a yellow solid. LC-MS (ES) m/z = 291 [M+H]+. NMR (400 MHz, DMSO-c/6): delta 3.81 (s, 3H), 3.83 (s, 3H), 4.59 (d, J = 5.8 Hz, 2H), 6.20 (d, J = 2.3 Hz, 1 H), 7.19 (d, J = 9.4 Hz, 1 H), 7.64 (d, J = 2.0 Hz, 1 H), 7.97 (dd, J = 9.0, 1 .9 Hz, 1 H), 8.64 (d, J = 2.0 Hz, 1 H), 8.96 (t, J = 5.6 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 (1-Methyl-1H-pyrazol-3-yl)methanamine, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; MEDINA, Jesus Raul; TIAN, Xinrong; NG DI MARCO, Christina; GRAYBILL, Todd L.; HEERDING, Dirk A.; LI, William Hoi Hong; MANGATT, Biju; MARTYR, Cuthbert D.; RIVERO, Raphael Anthony; (570 pag.)WO2019/49061; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 2458-26-6, name is 3-Phenyl-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 2458-26-6, name: 3-Phenyl-1H-pyrazole

Methyl 3-(3-phenyl- 1 H -pyrazol- 1 -yl)butanoate 3-Phenyl-1 H-pyrazole (250 mg, 1 .73 mmol), methyl crotonate (275 muIota, 2.60 mmol) and DBU (130 muIota, 0.87 mmol) were combined in acetonitrile (3.5 ml), under nitrogen. The reaction was stirred at 50 C for 18 h and by TLC the reaction was complete. All of the volatiles were removed in vacuo and the crude material was purified by column chromatography, eluting 15-25% ethyl acetate/petroleum spirits. The title compound was obtained as a colourless oil [32] mg, 76%). HPLC – rt 7.48 min > 98% purity at 254 nm; LRMS [M+H]+ 245.2 m/z; HRMS [M+H]+ 245.1285 m/z, found 245.1284 m/z; 1 H NMR (400 MHz, DMSO) delta 7.87 – 7.70 (m, 3H), 7.44 – 7.33 (m, 2H), 7.33 – 7.19 (m, 1 H), 6.66 (d, J = 2.3 Hz, 1 H), 4.93 – 4.62 (m, 1 H), 3.56 (s, 3H), 2.93 (ddd, J= 22.0, 16.0, 7.0 Hz, 2H), 1 .48 (d, J = 6.8 Hz, 3H); 13C NMR (101 MHz, DMSO) delta 170.8, 149.7, 133.5, 130.3, 128.6 (2C), 127.3, 125.0 (2C), 102.2, 54.0, 51 .5, 40.5, 20.9.

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; MONASH UNIVERSITY; THE UNIVERSITY OF WESTERN AUSTRALIA; BAELL, Jonathan; PIGGOTT, Matthew; RUSSELL, Stephanie; TOYNTON, Arthur; RAHMANI, Raphael; FERRINS, Lori; NGUYEN, Nghi; (178 pag.)WO2015/172196; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 31037-02-2, name is Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate, molecular formula is C7H11N3O2, 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 Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate

Carboxylate 62 (20.0 g, 118 mmol) in ethanol (100 mL) was treated with aqueous sodium hydroxide (50 mL, 3 M). The reaction mixture was heated to reflux and allowed to stir for 2 h and the ethanol removed under reduced pressure. The aqueous solution was cooled to 0 C and acidified with HCl (3 M) to pH 5. The white precipitate was collected by filtration and heated neat to 185 C in Kugelrohr oven under vacuum (1 mmHg) to afford titled compound 22 (10.0 g, 87%) as a light brown solid. MP: 73 – 74 C; IR (Diamond Cell, neat): 3395, 3134, 1643, 1556, 1517, 1431, 1344, 1268, 1207, 999, 928, 758, 632 cm-1; 1H NMR (300 MHz, Chloroform-d) delta 7.21 (d, J = 2.0 Hz, 1H), 5.49 (d, J = 2.0 Hz, 1H), 3.62 (s, 3H), 3.50 (br. s, 2H); 13C NMR (75 MHz, Chloroform-d) delta 144.6 (C), 138.2 (CH), 91.2 (CH), 34.3 (CH3); LRMS (ESI+) m/z: 98 (100, [M + H]+), 120 (50, [M + Na]+). This data matched that previously reported. 3

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 31037-02-2, its application will become more common.

Reference:
Article; Katte, Timothy A.; Reekie, Tristan A.; Werry, Eryn L.; Jorgensen, William T.; Boyd, Rochelle; Wong, Erick C.N.; Gulliver, Damien W.; Connor, Mark; Kassiou, Michael; European Journal of Medicinal Chemistry; vol. 136; (2017); p. 330 – 333;,
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. 96799-02-9, name is 5-(Furan-2-yl)-1H-pyrazol-3-amine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 5-(Furan-2-yl)-1H-pyrazol-3-amine

Synthesis of 2-(5-Amino-3-furan-2-yl-pyrazol-1-yl)-1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethanone Protocol T was followed using 3-Furan-2-yl-2H-pyrazol-5-ylamine, K2CO3, 2-Chloro-1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethanone and DMF. Column chromatography using 100% ethyl acetate afforded the title compound as a white solid. 1H NMR (400 MHz, CD6CO) delta 7.48-7.52 (m, 1H), 6.98-7.06 (m, 2H), 6.52-6.56 (m, 2H), 6.44-6.48 (m, 2H), 5.74 (s, 1H), 4.98 (s, 2H), 3.68-3.88 (m, 4H), 3.12-3.24 (m, 4H). MS (ES) M+H) expected=369.4, found 370.1.

According to the analysis of related databases, 96799-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ChemoCentryx, Inc.; US2004/162282; (2004); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 16034-46-1,Some common heterocyclic compound, 16034-46-1, name is 1-Methyl-1H-pyrazole-5-carboxylic acid, molecular formula is C5H6N2O2, 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 solution of tert-butyl {4-methyl-2-[3-(methylsulfonyl)benzyl]-1,3-thiazol-5-yl}carbamate (300 mg, 0.78 mmol) obtained in Example 233-F) in ethanol (2 mL) was added dropwise concentrated hydrochloric acid (0.600 mL) at room temperature, and the mixture was stirred at 50C for 1 hr. The reaction mixture was cooled to 0C, neutralized with 8N aqueous sodium hydroxide solution, adjusted to pH 10-11 with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in DMA (3 mL), and 1-methyl-1H-pyrazole-5-carboxylic acid (118 mg, 0.94 mmol), HATU (356 g, 0.94 mmol) and DIEA (0.068 mL, 0.39 mmol) were added at room temperature. The reaction mixture was stirred at 60C for 2 hr, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: hexane-ethyl acetate (1:4-0:1)] and basic silica gel column chromatography [eluent: hexane-ethyl acetate (1:9-0:1)], and crystallized from ethyl acetate-hexane to give the title compound (159 mg) as white crystals (yield 52%). MS (ESI+) : [M+H]+ 391. 1H NMR (300 MHz, DMSO-d6) delta 2.31 (3H, s), 3.31 (3H, s), 4.04 (3H, s), 4.37 (2H, s), 7.06 (1H, d, J = 1.9 Hz), 7.53 (1H, d, J = 1.9 Hz), 7.59-7.74 (2H, m), 7.80-7.87 (1H, m), 7.91 (1H, brs), 10.52 (1H, s).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-1H-pyrazole-5-carboxylic acid, its application will become more common.

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2530078; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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