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| | 4-Pyrazoleboronic acid pinacol ester Basic information |
| Product Name: | 4-Pyrazoleboronic acid pinacol ester | | Synonyms: | 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole,min.97%;4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, min. 97%;4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole4-Pyrazoleboronic acid pinacol ester;4-Pyrazoleboronic acid pinacol ester,97%;4-(4,4,5,5-TetraMethyl-1,3,2-dioxaborolan-2-yl)pyrazole;4-Pyrazoleboronic acid pinaol ester;1H-Pyrazole, 4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-;4-(tetraMethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole | | CAS: | 269410-08-4 | | MF: | C9H15BN2O2 | | MW: | 194.04 | | EINECS: | 629-131-7 | | Product Categories: | organic or inorganic borate;Pyrazole series;API intermediates;Boronic acid;OLED materials,pharm chemical,electronic;269410-08-4 | | Mol File: | 269410-08-4.mol |  |
| | 4-Pyrazoleboronic acid pinacol ester Chemical Properties |
| Melting point | 142-146 °C (lit.) | | Boiling point | 335.4±15.0 °C(Predicted) | | density | 1.09±0.1 g/cm3(Predicted) | | storage temp. | Keep in dark place,Sealed in dry,Room Temperature | | solubility | DMSO, Ethyl Acetate, Methanol | | pka | 13.36±0.50(Predicted) | | form | Powder | | color | Off-white to tan | | Water Solubility | insoluble | | InChI | InChI=1S/C9H15BN2O2/c1-8(2)9(3,4)14-10(13-8)7-5-11-12-6-7/h5-6H,1-4H3,(H,11,12) | | InChIKey | TVOJIBGZFYMWDT-UHFFFAOYSA-N | | SMILES | N1C=C(B2OC(C)(C)C(C)(C)O2)C=N1 | | CAS DataBase Reference | 269410-08-4(CAS DataBase Reference) |
| Hazard Codes | Xi,F | | Risk Statements | 36/37/38 | | Safety Statements | 26-36 | | WGK Germany | 3 | | Hazard Note | Irritant/Flammable | | TSCA | No | | HS Code | 29331990 | | Storage Class | 11 - Combustible Solids | | Hazard Classifications | Eye Irrit. 2
Skin Irrit. 2
STOT SE 3 |
| | 4-Pyrazoleboronic acid pinacol ester Usage And Synthesis |
| Chemical Properties | Off-white to tan powder | | Uses | 4-Pyrazoleboronic Acid Pinacol Ester is used in the preparation of Rho kinase (ROCK) inhibitors as wella s other biologically active compounds. | | Uses | 1H-Pyrazole-4-boronic acid pinacol ester is a useful reagent for Suzuki-Miyaura cross-couplings as well as Ruthenium-catalyzed asymmetric hydrogenation. It is also used as reagent for preparing VEGF, Aurora, RHO (ROCK), Janus Kinase 2, c-MET, ALK, S-nitrsoflutathione reductase, CDC7, Acetyl-CoA carboxylase inhibitors as well as other biologically active compounds. | | Uses | Reagent used for
- Suzuki-Miyaura cross-couplings
- Ruthenium-catalyzed asymmetric hydrogenation
Reagent used in preparation of inhibitors of many highly significant therapeutic enzymes and kinases containing the privileged scaffold pyrazole, including
- VEGF
- Aurora
- Rho (ROCK)
- Janus Kinase 2 (JAK)
- c-MET
- ALK
- S-nitrosoglutathione reductase
- CDC7
- Acetyl-CoA carboxylase
- Prosurvival Bcl-2 protein
- Viral RNA-Dependent RNA polymerase
- Long Chain Fatty Acid Elongase 6
- PI3
- AKT
- Chk1
- Protein Kinase B
| | Synthesis | General procedure for the synthesis of 4-pyrazole boronic acid pinacol ester from 1-(1-ethoxyethyl)-4-pyrazoleboronic acid pinacol ester: 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (60.00 g, 224 mmol) was mixed with cyclopentyl methyl ether (CPME. 120 mL) and 2,3-dimethyl-2,3-butanediol (26.49 g, 224 mmol) were mixed. The reaction mixture was cooled to 5-10 °C, then a solution of anhydrous hydroquinone (HQ) in CPME (3.1 M, 86.8 mL, 269 mmol) was slowly added over 15 min, followed by additional CPME (15 mL). The reaction mixture was stirred at 20-25 °C and the progress of the reaction was monitored by TLC.After 7 h, additional hydrochloric acid solution (3 mL, 9.3 mmol) was added to the reaction mixture and stirring was continued for 15 h to afford 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole hydrochloride, which did not require isolation. The temperature of the reaction mixture was raised to 20°C after addition of additional hydrochloric acid solution within 10 min. Additional CPME (10 mL) was added and the reaction mixture was stirred for 15 min and then cooled in an ice bath.After 3 h, the reaction mixture was filtered and the solid (triethylamine hydrochloride) was washed with cold CPME (3 x 60 mL). The filtrate and washings were combined to give 426 g of a solution containing 102.3 mg of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. The solution (8.15 g in total, 94% yield) was used directly in the next step. | | References | [1] Patent: WO2016/205487, 2016, A1. Location in patent: Page/Page column 27-28
[2] Patent: US2014/256941, 2014, A1. Location in patent: Paragraph 0166 |
| | 4-Pyrazoleboronic acid pinacol ester Preparation Products And Raw materials |
| Raw materials | tert-Butyl 4-iodopyrazole-1-carboxylate-->1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-->1,3,2-Dioxaborolan-2-amine, N,N,4,4,5,5-hexamethyl--->4-Bromopyrazole-->Bis(pinacolato)diboron-->1-Boc-4-bromopyrazole-->Hydrochloric acid-->Pinacol | | Preparation Products | 1-{2-[(Tetrahydro-2H-pyran-2-yl)oxy]ethyl}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-->1-Boc-pyrazole-4-boronic acid pinacol ester-->1-(2,2-difluoroethyl)-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-->4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-->tert-Butyl 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate-->4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-([2-(trimethylsilyl)ethoxy]methyl)-1H-pyrazole-->1-(2-Methoxyethyl)-4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-->4-hydroxypyrazole-->1-Cyclobutyl-4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-->1-(2-Tetrahydropyranyl)-1H-pyrazole-4-boronic acid pinacol ester-->2-(methylthio)-4-(1H-pyrazol-4-yl)pyrimidine-->tert-butyl (2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)carbamate |
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