Ozone → (7s)-n-Methoxy-7-{[(5-methoxy-2-methyl-1h-indol-3-yl)acetyl]amino}-n-methyl-7-(5-phenyl-1h-imidazol-2-yl)heptanamide

Participants

Reaction Steps

A solution of EDC.HCl (1.2 eq.), HOBt (1.2 eq.) and (5-methoxy-2-methyl-1H-indol-3-yl)acetic acid (1.2 eq.) in DMF was stirred for 1 hr at RT and was then added to a solution of the amine (QQ2) (1 eq.) and DIPEA (2 eq.) in DMF. The mixture was stirred overnight then more HATU (2 eq.) was added followed after 1 h by CH3ON(CH3)H.HCl (2 eq.). After stirring for a further 12 hours the crude was purified by preparative RP-HPLC, using H2O (0.1% TFA) and MeCN (+0.1% TFA) as eluents (column: C18). The desired fractions were lyophilized to afford the titled compound as a white solid. The compound was then extracted from sat. aq. NaHCO3 solution to obtain the free base. 1H NMR (400 MHz, DMSO-d6) δ: 10.62 (1H, s), 8.62 (1H, d, J=6.3 Hz), 8.03 (1H, s), 7.77 (2H, d, J=7.6 Hz), 7.52 (2H, t, J=7.6 Hz), 7.48-7.39 (1H, m), 7.10 (1H, d, J=8.6 Hz), 6.96 (1H, s), 6.64-6.56 (2H, m), 5.06-4.96 (1H, m), 3.69 (3H, s), 3.62 (3H, s), 3.60-3.45 (2H, m), 3.06 (3H, s), 2.35-2.26 (2H, m), 2.36-2.26 (5H, m), 1.50-1.18 (6H, m). MS (ES) C30H37N5O4 requires: 531, found: 532 (M+H)+.

Provenance & Evidence