Functionalization of Quinazolin‐4‐Ones Part 2^#: Reactivity of 2‐Amino‐3, 4, 5, or 6‐Nitrobenzoic Acids with Triphenylphosphine Thiocyanate, Alkyl Isothiocyanates, and Further Derivatization Reactions

Abstract

in Wiley Online Library (wileyonlinelibrary.com).2-amino-3, 4, 5, or 6-nitrobenzoic acids were reacted with PPh 3 (SCN) 2 and alkyl isothiocyanates to give 5, 6, 7, or 8-nitro-2-thioxo-3-substituted quinazolin-4-ones, respectively. The position of the nitro group was found to have significant influence on the outcome of the reactions. Similarly, the nature of the substituent at position 8 (NO 2 , NH 2 , NH(C═O)CH 3 ) in 8-substituted-2-methylthio quinazolin-4-ones was also found to significantly influence their reactivity towards morpholine. A selection of the products were also tested for in vitro antibacterial activity but little activity was observed. Scheme 3. Synthesis of 8-amino-2-morpholino quinazolines. (i) = morpholine, reflux, 3-72 h. (ii) = K 2 CO 3 , CH 3 I or benzyl bromide, acetone, reflux, 1.5 h. (iii) = SnCl 2 .

Functionalization of Quinazolin‐4‐ones Part 3: Synthesis, Structures Elucidation, DNA‐PK, PI3K, and Cytotoxicity of Novel 8‐Aryl‐2‐morpholino‐quinazolin‐4‐ones

“…The commercially available 5‐chloro‐2‐nitrobenzoic acid was reduced according to the previously reported procedure , giving 2‐amino‐5‐chlorobenzoic acid 7 , which was cyclized with freshly prepared triphenylphosphine thiocyanate to give compound 8 . S ‐methylation of the 2‐thioxo tautomer 8 followed by treatment with morpholine gave 6‐chloro‐2‐morpholinoquinazolin‐4‐one ( 9 ) according to the previously reported methods (Scheme ). The 6‐chloro atom of compound 9 directed the bromination with NBS to the 8‐position and gave 8‐bromo‐6‐chloro‐2‐morpholino quinazolin‐4‐one ( 10 ).…”