1,1'-Carbonyldiimidazole → (2R,4S)-ethyl 5-(3'-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate

Participants

Reaction Steps

To a solution of (45)-ethyl 5-(3′-chlorobiphenyl-4-yl)-4-(2-hydrazinyl-2-oxoacetamido)-2-methylpentanoate, intermediate 26, (542 mg, 1.25 mmol) in THF (16 mL) is added CDI (244 mg, 1.50 mmol) at room temperature. After stirring for 18 hour at room temperature, the reaction is quenched with H2O and 1M HCl and diluted in EtOAc. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O(0.1% TFA)/CH3CN) and by Chiral-HPLC (OJ-H 21×250 mm, EtOH(0.1% TFA)/Heptane=30/70) to give (2R,4S)-ethyl 5-(3′-chlorobiphenyl-4-yl)-2-methyl-4-(5-oxo-4,5-dihydro-1,3,4-oxadiazole-2-carboxamido)pentanoate (333 mg). HPLC retention time=1.74 minutes (condition A); MS 458.2 (M+1); 1 H NMR (400 MHz, DMSO-d6) δ ppm 1.07 (d, J=7.1 Hz, 3 H) 1.12 (t, J=7.1 Hz, 3 H) 1.58-1.74 (m, 1 H) 1.76-1.91 (m, 1 H) 2.45-2.50 (m, 1 H) 2.77 (dd, J=13.7, 7.9 Hz, 1 H) 2.86 (dd, J=13.7, 7.9 Hz, 1 H) 4.00 (q, J=7.1 Hz, 2 H) 4.06-4.22 (m, 1 H) 7.28 (d, J=8.1 Hz, 2 H) 7.37-7.42 (m, 1 H) 7.47 (t, J=7.8 Hz, 1 H) 7.58-7.66 (m, 3 H) 7.67-7.73 (m, 1 H) 8.86 (d, J=8.8 Hz, 1 H) 12.95 (s, 1 H).

Provenance & Evidence