Sodium Iodide → 1-(2-Thienyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]butanone

Participants

Reaction Conditions

Reaction Steps

To a hot (78° C.) mixture of 4-(5-fluoro-2-pyrimidinyl) piperazine (4.00 g, 22.0 mmol), 4-chloro-2'-butyrothienone (3.57 mL, 22.0 mmol) and triethylamine (6.97 mL, 50.0 mmol) in methylethyl ketone (125 mL) was added dropwise (1 h) a solution of NaI (4.8 g, 32.0 mmol) in methylethyl ketone (125 mL). The resulting mixture was refluxed for 22 h, then cooled at 23° C. and concentrated to dryness in vacuo. The residue was diluted with CH2Cl2 (400 mL) and the solution washed with aqueous NaOH solution (0.5N, 44 mL). Aqueous phase was separated and extracted with CH2Cl2 (2×10 mL). Organic extracts were combined, dried (MgSO4) and concentrated under reduced pressure to a crude material which was chromatographed on a silica gel column (5×16 cm) using a mixture 30-100% EtoAC in hexane. Appropriate fractions were combined and concentrated to afford a yellow solid, 2.0 g (27%). Recrystallization from Et2O gave an analytical sample, mp 77°-8° C. 1H NMR (CDCl3, 200 MHz) δ: 1.9-2.2 (m, CH2CH2CH2, 2H), 2.3-2.7 (m, 6H), 2.96 (t, J=7.0 Hz, COCH2, 2H), 3.6-3.9 (m, 4H), 7.0-7.2 (m, 1H), 7.5-7.7 (m, 1H), 7.7-7.8 (m, 1H), 8.18 (s, pyrimidinyl H, 2H); IR (KBr) ν: 1660, 1610, 1555, 1510, 1480, 1359 cm-1 ; UV (EtOH) λ: 248 (ε 19699), 284 (ε 6287 ). 330 (ε 1816).

Provenance & Evidence