Category: 449758-17-2

Electric Literature of 449758-17-2, A common heterocyclic compound, 449758-17-2, name is 1-(2-Tetrahydropyranyl)-1H-pyrazole, molecular formula is C8H12N2O, 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.

At -78C under N2, BuLi (1.6 M in hexane) (8.30 mL, 13.28 mmol) was added over 15 min to a solution of l-(-2-tetrahydropyranyl)-lH-pyrazole (2.00 g, 13.14 mmol) in THF (20.00 mL). This reaction was stirred at -78 C for 30 min. l-bromo-3-methylbutane (1.80 mL, 14.40 mmol) was added dropwise over 10 min to this mixture. After 3 h at – 78 C, the reaction mixture was warmed to rt overnight then quenched with water and few drops of an aqueous solution of HC1 3N was added. This mixture was extracted twice with EtOAc and once with DCM. The organic layers were combined and the solvent was evaporated until dryness. The residue was purified by column chromatography on silica gel (stationary phase: irregular SiOH, 15-40 muiotaeta, 40 g, mobile phase gradient from: 95% heptane, 5% MeOH to 75% heptane, 25% EtOAc). The pure fractions were collected and the solvent was evaporated until dryness to give: 1.23 g of intermediate 250 (42% yield) (and 60 mg of intermediate 251).

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; JANSSEN PHARMACEUTICA NV; STANSFIELD, Ian; QUEROLLE, Olivier, Alexis, Georges; LIGNY, Yannick, Aime, Eddy; GROSS, Gerhard, Max; JACOBY, Edgar; MEERPOEL, Lieven; GREEN, Simon, Richard; HYND, George; KULAGOWSKI, Janusz, Jozef; MACLEOD, Calum; MANN, Samuel, Edward; (472 pag.)WO2018/2217; (2018); 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., SDS of cas: 449758-17-2

n-BuLi (2.5 M, 40 mL, 0.016 mol) was added to a solution of 1- (tetrahydro-2H-pyran-2-yl) -1H-pyrazole (2.0 g, 0.013 mol) in anhydrous THF (10 mL) at -78 under nitrogen atmosphere. The resulting mixture was stirred at -78 for 30 min before 2-isopropoxy-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (2.7 g, 0.014 mol) was added dropwise. After addition, the reaction was held at -78 for 3 h. Excess base was quenched with aqueous HCl solution (1 M, 10 mL) and the mixture was warmed to 25 , then extracted with EtOAc (15 mL ×3) . The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (PE:EtOAc 5:1) to afford the title compound. MS: m/z 279.1 (M + 1) .1H NMR (400 MHz, DMSO-d6) delta 7.51 (s, 1H) , 6.64 (s, 1H) , 5.70 (d, J 8.5 Hz, 1H) , 3.89 (d, J 11.3 Hz, 1H) , 3.48 -3.61 (m, 1H) , 2.20 -2.33 (m, 1H) , 1.83-2.03 (m, 2H) , 1.43-1.69 (m, 3H) , 1.28 (d, J 4.8 Hz, 12H) .

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; MERCK SHARP & DOHME CORP.; COOKE, Andrew J.; PITTS, Daniel; JOHNSON, Adam; BESHORE, Douglas C.; HURZY, Danielle; MITCHELL, Helen; FRALEY, Mark; MCCOMAS, Casey; SCHIRRIPA, Kathy; MERCER, Swati P.; NANDA, Kausik; MENG, Dongfang; WU, Jane; BABAOGLU, Kerim; LI, Chun Sing; MAO, Qinghua; QI, Zhiqi; (156 pag.)WO2016/54807; (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: 449758-17-2, name is 1-(2-Tetrahydropyranyl)-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 449758-17-2, name: 1-(2-Tetrahydropyranyl)-1H-pyrazole

To a solution of 1 -tetrahydropyran-2-ylpyrazole (762 mg, 5 mmol, 1 equiv.) intetrahydrofuran (35 ml) cooled at -78C is added n-butyllithium (2.5M in hexanes) (2.2ml, 5.5 mmol, 1.1 equiv.) dropwise. The mixture is warmed to 0C for 10 minutes and then is warmed to ambient temperature for 10 minutes. It is cooled to -78C and a solution of 2-oxo-3 -(2-trimethylsilylethoxymethyl)- 1,3 -benzothiazole-6-carbaldehyde (1.55 g, 5 mmol, 1 equiv.) in tetrahydrofuran (7 ml) is added. The mixture is stirred at -78C for one hour, quenched with aqueous saturated ammonium chloride, and extracted with ethyl acetate. The extracts are dried over sodium sulfate, filtered, and concentrated to an oil which is purified by silica chromatography eluting with 0-45% ethyl acetate in hexanes to afford 6- [hydroxy-(1 -tetrahydropyran-2-ylpyrazol-3 -yl)methyl] -3-(2- trimethylsilylethoxymethyl)-1,3-benzothiazol-2-one (1 .99g, 4.31 mmol, 86%) as amixture of diastereomers. LCMS (low pH): r.t. 2.27 mm.

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-(2-Tetrahydropyranyl)-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ELI LILLY AND COMPANY; GARDINIER, Kevin Matthew; GERNERT, Douglas Linn; HAHN, Patric James; HOLLINSHEAD, Sean Patrick; KHILEVICH, Albert; MAYHUGH, Daniel Ray; ORNSTEIN, Paul Leslie; PORTER, Warren Jaye; REEL, Jon Kevin; SCHKERYANTZ, Jeffrey Michael; SPINAZZE, Patrick Gianpietro; STEVENS, Freddie Craig; WITKIN, Jeffrey Michael; (199 pag.)WO2015/183673; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 449758-17-2, name is 1-(2-Tetrahydropyranyl)-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 449758-17-2, Computed Properties of C8H12N2O

l-Tetrahydropyran-2-ylpyrazole (5.85 g, 38.44 mmol) was dissolved in THF (35 mL) and cooled to -35 C. n-Butyl lithium (18.5 mL of 2.5 M in hexanes, 46.25 mmol) was added dropwise and the solution was stirred for an additional 1 h at -35 C. Chloro(trimethyl) silane (5.4 mL, 42.55 mmol) was added dropwise and the reaction was allowed to warm to room temperature and stir for 3 h. At this point, 100 mL of a saturated ammonium chloride solution was added and the mixture was extracted with ether. The organics were separated, washed with brine, dried over magnesium sulfate and evaporated. The crude material was purified by silica gel chromatography eluting with 0- 50% ethyl acetate in hexanes to give trimethyl-(2-tetrahydropyran-2-ylpyrazol-3- yl)silane (6.88 g, 80%) as a clear oil. 1H NMR (400 MHz, DMSO-d6) d 7.47 (d, J = 1.6 Hz, 1H), 6.42 (d, J = 1.7 Hz, 1H), 5.30 (dd, J = 9.4, 2.3 Hz, 1H), 3.92 – 3.84 (m, 1H), 3.65 – 3.55 (m, 1H), 2.31 – 2.19 (m, 1H), 2.01 – 1.88 (m, 2H), 1.76 – 1.62 (m, 1H), 1.57 – 1.48 (m, 2H), 0.29 (s, 9H). ESI-MS m/z calc. 224.13449, found 225.3 (M+l)+; Retention time: 0.66 minutes (LC method D).

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; ABELA, Alexander Russell; CLEMENS, Jeremy J.; GROOTENHUIS, Peter Diederik Jan; HADIDA RUAH, Sara Sabina; ISHIHARA, Yoshihiro; KHATUYA, Haripada; MCCARTNEY, Jason; MILLER, Mark Thomas; PIERRE, Fabrice Jean Denis; TRAN, Joe Anh; ZHOU, Jinglan; (227 pag.)WO2019/195739; (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 449758-17-2 as follows. name: 1-(2-Tetrahydropyranyl)-1H-pyrazole

Preparation 2 6-[1-Hydroxy-1-(1-tetrahydropyran-2-yl-1H-pyrazol-5-yl)ethyl]-3-(methoxymethyl)-3H-1,3-benzothiazol-2-one (Racemic mixture of diasteromers) Add 1-tetrahydropyran-2-yl-pyrazole (1.5 Eq, 202 mmoles, 30.8 g)(Aldrich) and THF (900 mL) to a flame dried 2 L 3 neck round bottom flask and cool to -78 C. (dry ice/acetone bath). Add t-butyl lithium (2.5 M in THF)(1.5 Eq, 202 mmoles; 81.0 mL) dropwise, maintaining at least -68 C., and stir for 60 min at -78 C. Add a solution of 6-acetyl-3-(methoxymethyl)-3H-1,3-benzothiazol-2-one (32.0 g, 134 mmoles) in THF (450 mL) dropwise over 45 min, and stir at -78 for 30 min. Remove the dry ice bath and allow to warm to -50 C. and stir for 1 hr. (do not let temp. rise above -45 C.). Quench the reaction with MeOH (80 mL). Transfer to a separatory funnel, add EtOAc (2000 mL), and wash with water (500 mL) and then brine (500 mL). The organic layer is dried over Na2SO4, filter and concentrate to give a crude yellow oil. Purify the material by HPLC, eluting with hexanes/EtOAc (6:4) to yield 6-[1-hydroxy-1-(1-tetrahydropyran-2-yl-1H-pyrazol-5-yl)ethyl]-3-(methoxymethyl)-3H-1,3-benzothiazol-2-one as a white foam (44 g, 113 mmoles, 84% yield) (Racemic mixture of diasteromers). LCMS (Low) rt=1.76 min., M+1=288, and rt=1.86 min., M+1=288

According to the analysis of related databases, 449758-17-2, the application of this compound in the production field has become more and more popular.