Trifluoroacetic acid → (S)-N-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-2-(2-(5-(hydroxymethyl)thiazol-2-ylamino)acetamido)propanamide

Participants

Reaction Steps

To a suspension of material from Example 4 (26.7 mg, 0.050 mmol) in a mixture of EtOH/Water (4:1) (3 mL) is added sodium borohydride (18.4 mg, 0.486 mmol) in 3 portions over M5 min. The resulting pale white suspension is allowed to stir at room temp for 3 h. The reaction is diluted with EtOAC (75 mL) and saturated aqueous NH4Cl (12 mL). The water layer is back extracted with EtOAc (6×20 mL), the organic layers were combined, extracted with water (2×10 mL), brine (1×10 mL), dried over Na2SO4, filtered and evaporated to dryness. The aqueous layers were combined, evaporated to dryness, and purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 5% Solvent B to 45% Solvent B over 10 min, ret. T=4.12 min. The fractions containing the desired product were evaporated to dryness to give 7.3 mg (35%) of a 1:1 mixture of the title compound and its methyl ether as a colorless film as a TFA salt. LC/MS (Condition A): ret. T=0.8 min, (M+Na) 424.12 and ret. T=1.49 min, (M+Na) 444.12.

Provenance & Evidence