4-(4-hydroxyphenyl)-5-methyl-1,3-hiazol-2-amine synthesis

Yield:-

Reaction Conditions:

with iodine at 140;Microwave irradiation;

Steps:

4.1.5.18 1-(benzo[d][1,3]dioxol-5-yl)-N-(4-(4-hydroxyphenyl)-5-methylthiazol-2-yl)cyclopropanecarboxamide (5d)

General procedure: -(4-hydroxyphenyl)propan-1-one (15mg, 0.1mmol), thiourea (15mg, 0.2mmol) and iodine (25.4mg, 0.1mmol) were placed in an open vessel. The mixture was subjected to MW irradiation (100 Watt) in microwave for about 8-10min. Then the reaction mixture was checked with HPLC-MS, diluted with ethyl acetate and washed with H₂O (3×2ml), dried over Na₂SO₄ and concentrated under reduced pressure. The intermediate product, 4-(2-amino-5-methylthiazol-4-yl)phenol (19mg, 0.09mmol), was solved in anhydrous DMF (500μL) and conjugated, using the general procedure C, with 1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (19mg, 0.09mmol). The reaction mixture was stirred at T=50°C. After 20h the reaction was complete. The mixture was concentrated under vacuum and after extraction with ethyl acetate (3×3ml), washed with H₂O (3×2ml). The organic phase was dried over Na₂SO₄, concentrated under reduced pressure and purified by preparative HPLC. The peak of interest was concentrated to obtain the title compound with purity of >95% as determined by HPLC-MS (13.5mg, 35%).

References:

Liessi, Nara;Cichero, Elena;Pesce, Emanuela;Arkel, Maria;Salis, Annalisa;Tomati, Valeria;Paccagnella, Matteo;Damonte, Gianluca;Tasso, Bruno;Galietta, Luis J.V.;Pedemonte, Nicoletta;Fossa, Paola;Millo, Enrico [European Journal of Medicinal Chemistry,2018,vol. 144,p. 179 - 200]