Pyridine → HCID 86627964, compound

Participants

Reaction Steps

To a solution of (7S)-7-{[(5-methoxy-2-methyl-1H-indol-3-yl)acetyl]amino}-7-[5-(2-naphthyl)-1H-imidazol-2-yl]heptanoic acid (Free base of Example 107) (1 eq.) in EtOH (0.5 M solution) was added Na2CO3 (1 eq.). The heterogeneous mixture was stirred 40 min at RT then the solvent was removed under reduced pressure. DCM was added (0.14 M solution), the mixture was cooled at 0° C. with an ice-bath then TFAA (6 eq.) was added followed by pyridine (8 eq.). After 40 min at the same temperature some water was added and the product extracted with DCM. The collected organic phase were treated with brine and dried (Na2SO4) and after removing the solvent under reduced pressure 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 powder as a mixture of the ketone and hydrated form 1H NMR (500 MHz, pyridine) δ: 11.65-11.55 (0.5H, m), 11.50-11.38 (0.5H, m), 9.21-9.12 (0.5H, m), 8.71-8.63 (2H, m), 8.30-8.10 (1.5H, m), 8.00-7.79 (4.5H, m), 7.56-7.30 (4H, m), 7.09-6.97 (1H, m), 5.76-5.62 (1H, m), 4.11-3.96 (1.5, m), 3.85-3.71 (2.5H, m) 2.71-2.58 (1H, m), 2.55-2.41 (3.5H, m), 2.40-2.23 (2H, m), 2.21-2.03 (2H, m), 2.10-1.79 (1.5H, m), 1.70-1.00 (6H, m). MS (ES) C33H33F3N4O3 requires: 590, found: 609 (M+H2O+H)+.

Provenance & Evidence