Reaction Steps
Following the experimental and purification procedure of Step 1i, (1S,4R,6S,12S,16R)-7-trans-12-tert-butoxycarbonyl-amino-16-(7-methoxy-2-phenylquinolin-4-yloxy)-2,13-dioxo-3,14-diazatricyclo-[12.3.0.04,6]heptadec-7-ene-4-carboxylic acid ethyl ester (185 mg, 0.265 mmol) was reacted with 64 mg (1.6 mmol) of LiOH in 15.5 mL of 9:5:1.5 of THF/H2O/MeOH to afford (1S,4R,6S,12S,16R)-7-trans-12-tert-butoxycar-bonyiamino-16-(7-methoxy-2-phenylquinolin-4-yloxy)-2,13-dioxo-3,14-diazatricyclo[12.3.0.04,6]heptadec-7-ene-4-carboxylic acid (180 mg, 100%): 1H NMR (300 MHz, CD3OD) δ 1.24 (s, 9H), 1.33-1.43 (m, 1H), 1.61-1.97 (m, 6H), 2.10 (brs, 1H), 2.28-2.36 (m, 1H), 2.70 (m, 2H), 3.94 (s, 3H), 4.17 (d, J=10.6 Hz, 1H), 4.28 (d, J=4.8 Hz, 1H), 4.65-4.70 (m, 1H), 5.34 (dd, J=15.7, 5.9 Hz, 2H), 5.53-5.62 (m, 2H), 7.14 (d, J=9 Hz, 1H), 7.32 (s, 1H), 7.39 (s, 1H), 7.56 (m, 3H), 8.01-8.02 (m, 2H), 8.22 (d, J=9.2 Hz, 1H). LC-MS (Method E-retention time: 1.49), MS m/z 671 (M++1). HRMS m/z (M+H)+ calcd for C37H43N4O8: 671.3081, found 671.3080. Step 3j: Preparation of Compound 3, Example 3 (1S,4R,6S,12S,16R)-7-trans-[4-Cyclopropanesulfonyl-aminocarbonyl-16-(7-methoxy-2-phenylquinolin-4-yloxy)-2,13-dioxo-3,14-diazatricyclo[12.3.0.04,6]heptadec-7-en-12-yl]carbamic acid tert-butyl ester
