Reaction of 2-aryl(methyl)-4-cyano-5-hydrazino-1,3-oxazoles with aryl Isothiocyanates

Development of a Diversity-Oriented Approach to Oxazole-5-amide Libraries

“…Examples of stable 5-aminooxazoles are essentially limited to those bearing an electron-withdrawing functionality at the 4-position, typically a cyano group, [5][6][7][8][9] an amide, 10,11 or an additional heterocycle. [12][13][14] In order to resolve this difficulty, we recently reported 15 a preparation of N-Boc compound 2a via phosgene-mediated cyclization of R-acylaminonitrile 3a, followed by trapping with tert-butyl alcohol (Scheme 1). This Boc-protected intermediate served as a suitable precursor to a library of 2,4-diphenyloxazole-5-amides that were evaluated for their antiprion activity.…”

“…Particular difficulty in accessing target compounds 1 is presented by the general instability of free 5-aminooxazoles, which are prone to ring-opening in solution; thus, formation of the amide linkage through derivatization of such intermediates is precluded. Examples of stable 5-aminooxazoles are essentially limited to those bearing an electron-withdrawing functionality at the 4-position, typically a cyano group, − an amide, , or an additional heterocycle. − In order to resolve this difficulty, we recently reported a preparation of N -Boc compound 2a via phosgene-mediated cyclization of α-acylaminonitrile 3a , followed by trapping with tert -butyl alcohol (Scheme ). This Boc-protected intermediate served as a suitable precursor to a library of 2,4-diphenyloxazole-5-amides that were evaluated for their antiprion activity.…”

Synthesis of novel phosphorylated peptidomimetics which contain ω-haloalkyl and ω-thiocyanoethyl residues

“…It is known that 1,3-oxazole derivatives are reactive compounds and can be converted to other fiveand six-membered rings. [1][2][3][4][5][6][7][8][9][10] In addition, 1,3-oxazoles are unstable in an acidic medium and are cleaved by a water molecule to form acyclic products. 11,12 In the case of 4-functionalized 5-amino-1,3-oxazoles, this leads to formation of compounds of peptide nature.…”

Reactivity and diverse synthetic applications of acyl isothiocyanates

“…49 The 2-methyl/phenyl-4-cyano-5-hydrazino-1,3-oxazoles 67 add onto the acyl isothiocyanates 1 (Scheme 24). The reaction initially generated expected adducts 68 that were capable of prototropism.…”

“…In a similar fashion, acyl isothiocyanates reacted with diethyl 5-hydrazino-2-(4-methylphenyl)-1,3-oxazol-4-yl-phosphonate 71 to give the phosphorylated derivatives of 1,3,4-thiadiazoles 72 (Scheme 25). 50 In another approach to synthesize the 1,3,4-thiadiazole skeleton, the acyl thiosemicarbazides 74 from nicotinoyl/isonicotinoyl hydrazide 73 have been cyclized with phosgene in the presence of sodium acetate forming 1,3,4-thiadiazol-2(3H)-ones 75 in good to excellent yields (Scheme 26). 51 Some of these compounds exhibited significant anti-inflammatory activity.…”