ChemInform Abstract: Synthesis of 3,4‐Diaryl‐2(5H)‐furanones.

Abstract

The desired title compounds (IV) are obtained by reaction of the bromides (I) with phenylacetic acid (II) via the acetates (III).

Design and Synthesis of Celecoxib and Rofecoxib Analogues as Selective Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Sulfonamide and Methylsulfonyl Pharmacophores by an Azido Bioisostere

“…This difference is likely due to a greater electrostatic interaction between the dipolar azido group in pyrazole 13 and the charged guanidino moiety of Arg 513 in the secondary COX-2 pocket. Similar docking of the 1-(4-azidophenyl)-3-(4-methylphenyl)-5-trifluoromethylpyrazole regioisomer (10) in the active site of human COX-2 showed that the azido substituent did not insert into the secondary pocket since the ligand 10 extended parallel to the longitudinal axis of the hydrophobic primary COX-2 channel (cavity), in a manner characteristically observed for nonselective COX-2 inhibitors 17 as illustrated in Figure 4.…”

“…The azido analogue 17 of rofecoxib, where MeSO 2 is replaced by N 3 , was prepared starting with the bromination of 4-azidoacetophenone 14 9 using Br 2 according to a reported method. 10 The subsequent reaction of the bromo compound 15 with phenylacetic acid in the presence of (Et) 3 N gave 4-(4-azidophenyl)-3-phenyl-2(5H)furanone ( 17) that was formed via the intermediate ester 16 as illustrated in Scheme 2.…”

Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors: Synthesis and Structure−Activity Relationships

“…The initial synthesis of diarylspiro[2.4]cycloheptenes was accomplished according to route A of Scheme , and is shown in Scheme 3. The preparation of an early intermediate, the diaryl lactone 15 , was conveniently accomplished by the alkylation of 4-fluorophenylacetic acid with bromide 10 and subsequent ring closure of the resulting ester . DIBAL reduction of lactone 15 in THF yielded diol 16 , which was converted to the corresponding dichloride 5 with thionyl chloride in DMF.…”

“…The preparation of an early intermediate, the diaryl lactone 15, was conveniently accomplished by the alkylation of 4-fluorophenylacetic acid with bromide 10 and subsequent ring closure of the resulting ester. 23 of lactone 15 in THF yielded diol 16, which was converted to the corresponding dichloride 5 with thionyl chloride in DMF. Cyclopentene ring formation was achieved via double alkylation of dimethyl malonate with dichloride 5 to give the key intermediate 4.…”