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With manganese(IV) oxide In water at 80℃; for 0.75h; |
LXIV; 82; 83
Method LXIV: Examples 82 and 83: A solution of Example 49 (free base, 10.2 mg) in DMSO (800 μL) and H2O (200 μL) was heated to 80° C. and treated with MnO2 (85%, activated, from Sigma-Aldrich, 21 mg). After 45 min, the reaction was quickly cooled to 23° C. and filtered through a 0.45 micron Teflon filter. The filtrate was directly loaded onto a Teledyne Isco ‘gold’ 5.5 gram column and flashed (Eluent: 0.05% w/v aq. HCl/CH3CN 95:5→0:100), giving Example 82 (1.0 mg, 8.7% yield, higher-polarity product) as a monohydrochloride salt. 1H NMR (CD3OD, 300 MHz): δ (ppm) 7.60-7.39 (m, 4H), 5.48 (app. s, 1H), 5.38 (app. d, J=15.2 Hz, 1H), 5.05 (s, 1H), 4.36 (s, 2H), 4.36-4.34 (m, 2H), 3.60-3.40 (m, 2H), 3.32-3.10 (m, 2H), 2.20-2.05 (m, 4H), 1.69 (tt, J=7.6 Hz, 2H), 1.41 (qt, 7.6 Hz, 7.6 Hz, 2H), 0.93 (t, J=7.0 Hz, 3H). LCMS-ESI+: calc'd for C22H31N6O3: 427.2 (M+H+) and calc'd for C22H29N6O2: 409.2 (M-OH)+; Found: 409.1 (M-OH)+. In addition, Example 83 (5.7 mg, 50% yield, lower-polarity product) was obtained as a monohydrochloride salt. 1H NMR (CD3OD, 300 MHz): δ (ppm) 7.60-7.39 (m, 4H), 5.50 (s, 2H), 4.34 (q, J=7.0 Hz, 2H), 4.33 (s, 2H), 3.48-3.39 (m, 2H), 3.20-3.04 (m, 2H), 2.20-2.05 (m, 2H), 2.05-1.90 (m, 2H), 1.70 (ft, J=7.6 Hz, 7.6 Hz, 2H), 1.42 (qt, J=7.6 Hz, 7.6 Hz, 2H), 0.93 (t, J=7.6 Hz, 3H). LCMS-ESI+: calc'd for C22H29N6O3: 425.2 (M+H+); Found: 425.2 (M+H+). |