Trifluoroacetic acid → 3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]-N-[2-hydroxy-1(S)-[(1H-imidazol-4-yl)methyl]ethyl]succinamic acid benzyl ester

Participants

Reaction Steps

According to the procedure described in Example 1(c) for the preparation of N-(8-oxo-4-oxa-1,7-diaza-tricyclo-[9.6.1.012,17 ]-octadeca-11(18),12,14,16-tetraen-9S-yl)-3(R)-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl ester, 3(R)-(t-butoxycarbonylamino)-N-[2-hydroxy-1(S)-[(1H-imidazol-4-yl)methyl]ethyl]succinamic acid benzyl ester was deprotected, and the resultant crude amine salt was condensed with 3-(biphenyl-4-yl)-2,5-dimethoxy-tetrahydrofuran (produced as described in Example 1(a)) in 1,2-dichloroethane in the presence of trifluoroacetic acid to give in 37% yield 3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]-N-[2-hydroxy-1(S)-[(1H-imidazol-4-yl)methyl]ethyl]succinamic acid benzyl ester as a yellow solid. 1H NMR (CDCl3): δ 7.65-7.59 (m, 4H), 7.53 (d, 2H, J=8.5 Hz), 7.45 (t, 2H, J=7.4 Hz), 7.37-7.26 (m, 7H), 6.95 (s, 1H), 6.70 (t, 1H, J=2.2 Hz), 6.65 (s, 1H), 6.52 (s, 1H), 6.45 (bs, 1H), 5.10 (s, 2H), 5.06-5.02 (m, 1H), 4.13-4.11 (m, 1H), 3.69 (dd, 1H, J=3.9, 11.6 Hz), 3.56 (dd, 1H, J=4.8, 11.8 Hz), 3.42 (dd, 1H, J=5.5, 16.9 Hz), 3.06 (dd, 1H, J=8.8, 16.9 Hz), 2.84 (t, 2H, J=4.8 Hz). Anal. for C33H32N4O4.0.8H2O0 0.15 MTBE: C, 70.34; H, 6.19; N, 9.72. Found: C, 70.51; H, 6.05; N, 10.15 .

Provenance & Evidence