1254473-74-9

Basic information

• Product Name: 5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1H-Indazole
• Synonyms: 5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1H-Indazole;5-(tert-butyl-dimethyl-silanyloxy)-1H-indazole;5-((tert-butyldimethylsilyl)oxy)-1H-indazole;1H-Indazole, 5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-
• CAS NO: 1254473-74-9
• Molecular Formula: C₁₃H₂₀N₂OSi
• Molecular Weight: 248.3962
• Mol File: 1254473-74-9.mol
• Article Data: 24

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1H-Indazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1H-Indazole(1254473-74-9)
• EPA Substance Registry System: 5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1H-Indazole(1254473-74-9)

Safety Data

• Hazardous Substances Data: 1254473-74-9(Hazardous Substances Data)

Usage

Synthesis

1H-indazol-5-ol (1.00 g, 7.45 mmol) dissolved in 20 mL of anhydrous methylene chloride was added to a 100 mL round bottom flask. Tert-butyldimethylsilyl chloride (1.69 g, 11.18 mmol) and imidazole (0.51 g, 7.45 mmol) were added to the reaction vessel producing a cloudy white mixture. Lastly, N,Ndiisopropylethylamine (1.95 mL, 11.18 mmol) was added, giving a clear solution.?The reaction was stirred overnight at room temperature. Methylene chloride was used to dilute the reaction followed by washing with NaCl (2x). The organic layer was dried over MgSO4, concentrated in vacuo, and purified using flash chromatography with a 20% EtOAc/Hexane gradient to give 5- ((tert-butyldimethylsilyl)oxy)-1H-indazole (5a) (1.72g, 93%).?1H NMR (DMSO – d6, 400 MHz) δ: 12.91 (s, 1H), 7.92 (s, 1H), 7.41 (d, J=9.0 Hz, 1H), 7.12 (d, J=1.5 Hz, 1H), 6.91 (dd, J = 8.8, 2.3 Hz, 1H), 0.96 (s, 9H), 0.18 (s, 6H).

Upstream product

• 15579-15-4 5-hydroxy-1H-indazole 
• 18162-48-6 tert-butyldimethylsilyl chloride 

Downstream Products

• 1254473-76-1 5-(tert-butyl-dimethyl-silanyloxy)-3-iodo-1H-indazole 

Relevant articles and documents

Design, synthesis, and Structure–Activity Relationships (SAR) of 3-vinylindazole derivatives as new selective tropomyosin receptor kinases (Trk) inhibitors

Neurotrophic receptor tyrosine kinase (NTRK) fusions are oncogenic drivers for a variety of adult and pediatric tumors, validated by the US FDA approval of small molecular Trk inhibitors Larotrectinib (1, LOXO-101) and Entrectinib (2). However, gene mutation mediated resistance becomes a major challenge for Trk inhibitor therapies. Herein, we report the design, synthesis and Structure–Activity Relationship investigation of a series of 3-vinylindazole derivatives as new Trk inhibitors with low nanomolar potencies. A representative compound, 7mb, binds to TrkA/B/C with Kd values of 1.6, 3.1 and 4.9 nM, and suppresses their kinase functions with IC50 values of 1.6, 2.9 and 2.0 nM, respectively, but is obviously less potent for the majority of a panel of 403 wild-type kinases in a KINOMEscan selectivity investigation. The compound also potently suppresses proliferation of a panel of BaF3 cells stably transformed with NTRK fusions with IC50 values in low nM ranges. Additionally, the compound exhibits strong inhibition against the Larotrectinib-resistant cells with NTRK1-G667C or NTRK3-G696A mutations with IC50 values of 0.031 and 0.018 μM, respectively. Although the relatively poor oral bioavailability of 7mb will limit its further development, this compound may be utilized a lead molecule for further structural optimization.

INDAZOLE COMPOUNDS

Disclosed herein are indazole compounds and methods of treating diseases and/or conditions (e.g., cancer) with the indazole compounds disclosed herein.

INDAZOLE BASED COMPOUNDS AND ASSOCIATED METHODS OF USE

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

SYNTHETIC METHOD OF METABOLITES OF ADB-FUBINACA

The present invention relates to a method for synthesizing a metabolite of ADB-fubinaka to develop an evaluation method whether ADB-fubinaka is taken, which is a novel hemp-like component. Through the method for synthesizing the metabolite of ADB-fubinaka