Trifluoroacetic acid → N-(4-methylthiazol-2-yl)-2-(piperazin-1-yl)acetamide

Participants

Reaction Steps

To a solution of tert-butyl 4-(2-(4-methylthiazol-2-ylamino)-2-oxoethyl)piperazine-1-carboxylate (0.072 g, 0.21 mmol) in dichloromethane (2 ml) was added trifluoroacetic acid (2.5 ml). The reaction mixture was stirred at room temperature for 1.5 h, then the solvents were removed under reduced pressure to afford N-(4-methylthiazol-2-yl)-2-(piperazin-1-yl)acetamide (a semi-solid material) that was dried in vacuo. To a mixture of this material (supposedly 0.20 mmol) and isopropanol (3.5 ml) was added 2-amino-4,5-dichloro-3-nitropyridine (0.031 g, 0.15 mmol) followed by diisopropylethylamine (0.14 ml, 0.80 mmol). The reaction mixture was stirred at 45° C. for 20 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 20% ethyl acetate in dichloromethane. The title compound was obtained as an orange solid (0.044 g, 54%). 1H-NMR (500 MHz, DMSO-d6) 2.26 (s, 3H, CH3), 2.65 (br s, 4H, piperazine N(CH2)2), 3.10 (br s, 4H, piperazine N(CH2)2), 3.33 (s, 2H, NCH2CO), 6.76 (s, 1H, thiazole 5-H), 6.96 (br s, 2H, NH2), 8.07 (s, 1H, 6-H), 11.75 (s, 1H, CONH);

Provenance & Evidence