1-[5-Methoxy-2-nitro-4-[3-(1-pyrrolidinyl)propoxy]phenyl]cyclobutanecarbonitrile → 5'-Methoxy-6'-[3-(1-pyrrolidinyl)propoxy]spiro[cyclobutane-1,3'-[3H]indol]-2'-amine

Participants

Reaction Conditions

Reaction Steps

A solution of 1-(5-methoxy-2-nitro-4-(3-(pyrrolidin-1-yl)propoxy)phenyl)cyclobutanecarbonitrile (0.063 g, 1.742 mmol), from Step 4, in acetic acid (10 mL), was treated with 10% Pd/C (0.56 g, 0.523 mmol). The mixture was stirred under an atmosphere of hydrogen at 80° C. for 5 hours. The catalyst was filtered off and washed with EtOH. The filtrate was concentrated and resulting crude product was purification by flash chromatography (silica gel, 15-25% 3N methanolic ammonia/dichloromethane) to afford 0.161 g (28%) of 5′-methoxy-6′-(3-(pyrrolidin-1-yl)propoxy)spiro[cyclobutane-1,3′-indol]-2′-amine 1H NMR (400 MHz, METHANOL-D4) δ 7.28 (s, 1H), 6.71 (s, 1H), 4.11 (t, J=5.7 Hz, 2H), 3.88 (s, 3H), 3.27-3.19 (m, 6H), 2.63 (t, J=9.9 Hz, 2H), 2.52-2.42 (m, 1H), 2.38 (dd, J=13.0, 10.4 Hz, 2H), 2.31-2.22 (m, 1H), 2.17 (dt, J=12.8, 6.2 Hz, 2H), 2.04 (t, J=6.8 Hz, 6H). MS (ESI) m/z 330 (M+H)+.

Provenance & Evidence