Pyridine → HCID 66893065, compound

Participants

Reaction Steps

Dry pyridine (20 μL, 0.24 mmol) and 2-chlorobenzenesulfonyl chloride (25 μL, 0.18 mmol) were added to a solution of 4-(5-amino-benzofuran-7-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (40 mg, 0.12 mmol; obtained in Step 2) in a mixture of dry DCM:THF (2:1; 3 mL). The resulting mixture was stirred for 3 h and volatiles were then evaporated. The product was purified using flashtube (15% MeOH in DCM). The residue was dissolved in TFA:water (9:1; 2 mL) and the mixture was stirred at room temperature for 30 min to accomplish removal of the N-t-BOC group. The reaction mixture was made basic by addition of saturated aqueous Na2CO3 (pH 8-9) and extracted with DCM (×2). The organic layers were combined, dried (Na2SO4) and concentrated. The crude product was purified with preparative HPLC (System A; 10-40% MeCN). Pure fractions were combined and concentrated. The obtained TFA salt was dissolved in MeOH and 1 M HCl in ether was added, followed by concentration to give the title compound (10 mg, 18%) as a light yellow solid. HPLC 100%, RT=1.38 min (System A; 10-97% MeCN over 3 min), 100%, RT=1.23 min (System B; 10-97% MeCN over 3 min). 1H NMR (400 MHz, methanol-d4) δ ppm 2.86-2.92 (m, 4H) 3.25-3.28 (m, 4H) 4.04-4.08 (m, 2H) 6.73 (d, J=2.26 Hz, 1H) 7.15 (d, J=2.01 Hz, 1H) 7.26-7.31 (m, 1H) 7.32 (d, J=2.26 Hz, 1H) 7.42-7.47 (m, 1H) 7.47-7.52 (m, 1H) 7.70 (d, J=2.26 Hz, 1H) 7.90 (dd, J=8.03, 1.51 Hz, 1H). MS (ESI+) for C19H20ClN3O3S m/z 406 (M+H).

Provenance & Evidence