Reaction Steps
Isobutyl chloroformate (3.0 mg, 0.022 mmol) was added to a 0° C. solution of (3R,6R)-6-benzyl-7-((4S,7S,10aS)-7-(methoxycarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylamino)-3-((4S,7S,10aS)-7-(methoxycarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamoyl)-7-oxoheptanoic acid (16 mg, 0.021 mmol) and NMM (2.5 mg, 0.025 mmol) in DCM (0.1 mL). After 30 min at 0° C., NH4OH (1.5 mg, 0.041 mmol) was added. The ice bath was removed and the reaction mixture was stirred at rt for 1 hr. The reaction mixture was concentrated. The residue was purified by RP prep-HPLC (Method A) to give methyl (4S,7S,10aS)-4-(((2R,5R)-7-amino-2-benzyl-5-(((4S,7S,10aS)-7-(methoxycarbonyl)-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepin-4-yl)carbamoyl)-7-oxoheptanoyl)amino)-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate (8.5 mg, 0.010 mmol, 53% yield) as a colorless oil. Anal. Calcd. for C37H51N5O9S2 m/z 773.7. found: 7749.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.53 (1H, d, J=6.6 Hz), 7.28-7.11 (6H, m), 6.38 (1H, br. s.), 6.18 (1H, br. s.), 5.43-5.36 (2H, m), 5.20-5.14 (1H, m), 5.14-5.00 (3H, m), 4.03-3.80 (2H, m), 3.72 (3H, s), 3.69 (3H, s), 3.25-3.08 (2H, m), 2.97-2.89 (1H, m), 2.89-2.80 (2H, m), 2.79-2.66 (2H, m), 2.61-2.36 (4H, m), 2.32 (1H, dd, J=14.8, 4.9 Hz), 2.24-2.15 (1H, m), 2.08-1.94 (4H, m), 1.86-1.76 (1H, m), 1.74-1.57 (8H, m), 1.57-1.46 (2H, m).
