The coupling of 2-amino-4-methylthiophene-3-carboxylic acid ethyl ester (I) with N-(tert-butoxycarbonyl)-L-alanine (II) by means of isobutyl chloroformate and NMM, followed by cyclization with triphenylphosphine in CCl4 gives the thieno-oxazinone (III), which is deprotected with TFA yielding (IV) with a free amino group that is acylated with cinnamic acid by means of DEC and DIEA.
The coupling of 2-amino-4-methylthiophene-3-carboxylic acid ethyl ester (I) with N-(tert-butoxycarbonyl)-L-alanine (II) by means of isobutyl chloroformate and NMM, followed by cyclization with triphenylphosphine in CCl4 gives the thieno-oxazinone (III), which is deprotected with TFA yielding (IV) with a free amino group that is acylated with 3-(5-bromothien-2-yl)-2(E)-propenoic acid by means of DEC and DIEA.
The cyclization of 2-amino-4-methylthiophene-3-carboxylic acid (I) with N-(tert-butoxycarbonyl)-L-alanine (II), by means of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (DEC) and HOBT in DMF gives the protected thienooxazinone (III), which is deprotected with trifluoroacetic acid in dichloro methane yielding 2-(1(S)-aminoethyl)-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one (IV). Finally, this compound is acylated with 4-oxo-4-phenyl-2(E)-butenoic acid (VI) by means of DEC and diisopropylethylamine in DMF.