Cesium carbonate → HCID 10112406, compound

Participants

Reaction Conditions

Reaction Steps

{1-[2-(5-Hydroxy-benzoimidazol-1-yl)-quinolin-8-yl]-piperidin-4-yl}-carbamic acid tert-butyl ester H (200 mg, 0.435 mmol) was dissolved in 1.5 mL of anhydrous DMF under an atmosphere of dry N2. To this solution was added Cs2CO3 (170 mg, 0.520 mmol) followed by cyclopropyl methane bromide (46 mL, 0.48 mMol). The reaction mixture was subsequently heated to 65° C. and stirred at this temperature for 4 hours. The reaction mixture was then cooled to ambient temperature and partitioned between EtOAc and water. The EtOAc layer was washed 4 more times with water and then with brine. The EtOAc was then dried over Na2SO4, filtered and concentrated under vacuum and the resulting green oil was chromatographed on flash silica gel eluting with MeOH/dichloromethane (DCM) (2:98) to give the a green oil. The oil was dissolved in 1.5 mL of TFA under an atmosphere of dry N2. The reaction mixture was stirred at ambient temperature for 10 minutes after which time it was concentrated under vacuum and the resulting residue was partitioned between DCM and aqueous 0.1 N NaOH. The DCM layer was then washed with basic brine (pH =10), dried over Na2SO4, filtered and concentrated under vacuum to give 118 mg 1-[2-(5-Cyclopropylmethoxy-benzoimidazol-1-yl)-quinolin-8-yl]-piperidin-4-ylamine as a yellow solid. C.I. m/z 414 [M+1]; 1H NMR (CDCl3) δ 8.63 (s, 1 H), 8.37 (d, J=8.9 Hz, 1 H), 8.27 (d, J=8.7 Hz, 1 H), 7.65 (d, J=8.7 Hz, 1 H), 7.44 (m, 2 H), 7.30 (d, J=2.5 Hz, 1 H), 7.24 (m, 1 H), 7.09 (dd, J=2.5, 8.9 Hz, 1 H), 3.87 (m, 4 H), 2.87 (m, 3 H), 2.03 (m, 2 H), 1.81 (m, 2 H), 1.56 (brs, 2 H), 1.32 (m, 1 H), 0.66 (m, 2 H), 0.39 (m, 2 H).

Provenance & Evidence