The Davis–Beirut Reaction: N¹,N²-Disubstituted-1H-Indazolones via 1,6-Electrophilic Addition to 3-Alkoxy-2H-Indazoles

Abstract

A variety of electrophiles (anhydrides, acid chlorides, carbonochloridates, sulfonyl chlorides, and alkyl bromides) react with 3-methoxy-2H-indazole (1a), benzoxazin[3,2-b]indazole (1d), and oxazolino[3,2-b]indazole (1e) – substrates available by the Davis-Beirut reaction – to yield a diverse set of N1,N2-disubstituted-1H-indazolones. With certain electrophiles, an AERORC (Addition of the Electrophile, Ring Opening, and Ring Closure) process on indazole 1d results in indazoloindazolone formation. An intriguing aspect of these N1,N2-disubstituted-1H-indazolones is that they are poised for diversification through, for example, azide-alkyne cycloaddition chemistry reported here.

7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove

“…Azides 8 and 9 were prepared from their corresponding bromoketone and bromoalkane, respectively (Figure 2). 37,38 …”

“…(±)-2-(1-Bromopropan-2-yl)-1-((3-isopropylisoxazol-5-yl)methyl)-1H-indazol-3(2H)-one 37 (149 mg, 394 mmol) was added to a 5–10 mL microwave vial and dissolved in DMF (2.0 mL). Sodium azide (30.7 mg, 473 mmol) was added and the vial was sealed and placed in an oil bath at 60 °C for 3 hours.…”

Catalytic Stereoselective Synthesis of Diverse Oxindoles and Spirooxindoles from Isatins

“…We began by exploring one-pot reaction conditions that utilize in situ generated azides, prepared from the corresponding amine using the shelf-stable diazotransfer reagent 1H-imidazole-1-sulfonyl azide ( 21 ) (Scheme 3, eq 1). 17 Unfortunately, this method did not work for these oxindole substrates due to side reactions and decomposition of starting material under the diazo transfer conditions. Several solvent combinations (THF, MeOH/THF, DCM), copper reagents, and conditions (i.e.…”

A One-Pot–Three-Step Route to Triazolotriazepinoindazolones from Oxazolino-2H-indazoles

“…In previous reports, we have shown that oxazolino-2 H -indazoles, available via the Davis-Beirut reaction, 4 can be converted into N 2 -substituted indazolones by treatment with various nucleophiles 5 or N 1 , N 2 -disubstituted indazolones by treatment with various electrophiles 6 (Scheme 1). The chemistry reported here combines this electrophilic indazole → indazolone reaction with an IAAC to provide an efficient route to triazolotriazepinoindazolones {e.g., 12,13-dihydro[1,2,3]triazolo-[1′,5′:5,6][1,2,5]triazepino[1,2-a]in-dazol-10(4 H )-ones}.…”