Pyridine → HCID 58717686, compound

Participants

Reaction Steps

A solution of (2S)-(2-amino-5-bromo-benzoylamino)-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester (54.5 mg, 0.10 mmol) from example 294 in 1 mL dry CH2Cl2 was treated with 3,5,5-trimethylhexanoyl chloride(1.2 eq., 23 microL, 0.12 mmol) and pyridine (1.5 eq., 12 microL, 0.15 mmol) in succession and stirred under an atmosphere of dry N2 for one hour, then concentrated in vacuo. The crude residue was purified by flash column chromatography (hexanes, EtOAc) to afford the desired amide, (2S)-[5-Bromo-2-(3,3,5-trimethyl-hexanoylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid methyl ester, in quantitative yield (68 mg, 100%). The methyl ester (20 mg, 29 micromol) was dissolved in 2.0 mL THF and 0.5 mL MeOH and saponified with 2N aqueous LiOH solution (0.25 mL), as described in general procedure C, to afford the title compound, (2S)-[5-Bromo-2-(3,3,5-trimethyl-hexanoylamino)-benzoylamino]-3-(2′-phenoxy-biphenyl-4-yl)-propionic acid (20 mg, 100%), as a white solid. LCMS 673 (M+1)+. 1H NMR (400 MHz, CDCl3) 10.74 [s, 1H], 8.51 [d, 1H], 7.51 [m, 3H], 7.43 [m, 2H], 7.27–7.30 [m, 2H], 7.16–7.26 [m, 5H], 6.98 [d, 2H], 6.88 [d, 2H], 6.59 [d, 1H], 5.03 [dd, 1H], 3.28 [dq, 2H], 2.36 [m, 1H], 2.14 [m, 1H], 1.11–1.25 [m, 3H], 1.00 [s, 3H], 0.92 [s, 3H], 0.91 [d, 6H].

Provenance & Evidence