Piperidin-4-ol → N-(5-{5-[(4-hydroxypiperidin-1-yl)carbonyl]-2-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide

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Reaction Steps

5-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-carboxylic acid, Compound (4) (50 mg; 0.18 mmol; 1 eq.), is dissolved in THF (8 ml). PyBOP (138.2 mg; 0.27 mmol; 1.50 eq.), 4-hydroxypiperidine (53.7 mg; 0.53 mmol; 3 eq.) and DIEA (0.06 ml; 0.35 mmol; 2 eq.) are added successively. The reaction mixture is stirred at room temperature for 2 hours. The solvents are evaporated and the crude product is suspended in MeCN, filtered and washed several times with MeCN, affording Compound (7) as brown solid (15.2 mg; 23%). 1H NMR (DMSO-d6) δ 1.30-1.45 (m, 2H), 1.72-1.85 (m, 2H), 2.14 (s, 3H), 2.42 (s, 3H), 3.25-3.38 (m, 2H), 3.75 (m, 1H), 3.85-4.02 (m, 2H), 4.80 (d, J=6 Hz, 1H), 7.13 (d, J=6 Hz, 1H), 7.36 (d, J=6 Hz, 1H), 12.18 (br s, 1H). M−(ESI): 364.12; M+(ESI): 366.10. HPLC, Rt: 2.35 min (purity: 97.9%).

Provenance & Evidence