Acetic Acid → HCID 50904992, compound

Participants

Reaction Steps

2-{[4-bromo-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]oxy}-5-chloropyridine-3-carbaldehyde (32, 2.60 g, 6.38 mmol) was dissolved in anhydrous dichloroethane (63.8 mL, 0.1M) and treated with 1-(methylsulfonyl)piperazine (2.10 g, 12.8 mmol, 2 equiv.) and acetic acid (3.65 mL, 63.8 mmol, 10 equiv.). After 30 minutes the solution formed a thick suspension and was treated with sodium triacetoxyborohydride (1.76 g, 8.29 mmol, 1.3 equiv) in small portions over 1 hour. After completion of this addition, the reaction was allowed to stir an additional 2 h at ambient temperature. Upon completion as judged by TLC and LCMS, the reaction was quenched by the slow addition of water (20 mL) and NaHCO3. The mixture was extracted 3× with dichloromethane (3×30 mL), and the combined organic layers were dried over MgSO4. The crude mixture was purified using flash column chromatography (Redisep SiO2, 80 g, 0-100% EtOAc/hexanes) to provide pure 198: 1H NMR (300 MHz, CDCl3) δ 7.89 (d, 1H, J=2.5 Hz), 7.84 (d, 1H, J=2.5 Hz), 7.56 (d, 1H, J=8.8 Hz), 7.33 (d, 1H, 8.8 Hz), 4.53 (d, 2H, J=7.1 Hz), 3.82 (s, 2H), 3.33 (m, 4H), 2.83 (s, 3H), 2.74 (m, 4H), 1.41 (m, 1H), 0.69 (m, 2H), 0.52 (dd, 2H, J=10.8, 5.1 Hz, 2H). LRMS m/z (M+H) 556.9 found, 556.9 required.

Provenance & Evidence