2-Benzoxazolone ring

Benzoxazolone ring opening l-(o-Hydroxyaryl)hydantoin ring... 

A recent case described the synthesis of more stable bioisosteres of inhibitors of the insulin-like growth factor-1 receptor kinase (Figure 15.43). Based on the structure of AG 538 ° which contains two catechol rings and is sensitive to oxidation in cell, a new series of kinase inhibitors were developed. The catechol moiety was replaced by a benzoxazolone ring resistant to oxidation yielding two compounds GB19 and AGL2263 which maintain same potency as AG 538. 

Photochemical studies on the ring degradation of 3-hydroxy-l,2-benzisoxazole also yielded benzoxazolone, and (40), (41) and (42) (Scheme 14) were believed to be potential intermediates. Low temperature IR measurements indicated the presence of (42) during the photochemical reaction (73JA919, 71DIS(B)4483, 71JOC1088). Sensitization studies indicate that the rearrangement is predominantly a triplet reaction, and the keto tautomer is believed to be the key orientation for the photolysis. 

A. Vigroux, M. Bergon, C. Zedde, Cyclization-Activated Prodrugs A-(Substituted 2-Hydroxyphenyl and 2-Hydroxypropyl)carbamates Based on Ring-Opened Derivatives of Active Benzoxazolones and Oxazohdinones as Mutual Prodrugs of Acetaminophen , J. Med. Chem. 1995, 38, 3983-3994. 

DAIB-induced conversions of the anthranilamides 195 and salicylamides 196 to the benzimidazolones 197 and benzoxazolones 198, respectively, and similar rearrangements of two representative pyridinecarboxamides, are recent examples of direct heterocyclic ring-construction by the iodine(III)-Hofmann pathway (Scheme 57) (01S541). These reactions may be contrasted with BTIB-oxidations of the 2-aminonicotinamides 67 and amidopyridones 69 in aqueous DMF (Section II.A.2) which lead, without rearrangement, to N-N and N-O bond formation (97SC2217). 

Silylation-amination fails with 5-ring-hydroxy-N-heterocycles such as 2-benzoxazolone since, at temperatures of I30°C, the 2-trimethylsilyloxy-benzoxazole (190) is in equilibrium with its open form 191 (73LA772), which reacts readily with benzylamine to eventually form N,N -dibenzylurea (CftHjCHj—NH-CO—NH—CH2C6H5). The silylation-amination procedure has been applied to the amination of 6-oxadihydro-uracil (193) with benzylamine to 194 (77JMCI34). The 5-deazapteridine derivative 195 affords, with ammonia/HMDS in the presence of p-toluenesulfonic acid, the diaminated product 1% in 74% yield (86JMC709). 

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