Diisopropylethylamine → HCID 70558977, compound

Participants

Reaction Steps

To a solution of 3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)propan-1-amine (200 mg, 0.458 mmol), monoethylmalonate (91 mg, 0.687 mmol) and DIPEA (178 mg, 1.37 mmol) in DMF (5 mL) is added TBTU (191 mg, 0.596 mmol). The mixture is stirred at rt for 18 h. The solution is diluted with EA (50 mL) and washed twice with sat aq. NaHCO3 solution (50 mL) followed by brine (50 mL). The org. extract is dried over Na2SO4, filtered and concentrated to give crude ethyl 3-((3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy) propyl)amino)-3-oxopropanoate (298 mg) as a yellow oil; LC-MS: tR=1.19 min, [M+H]+=551.38. This material is dissolved in methanol (2 mL), THF (2 mL) and 2 N aq. LiOH (1 mL). The solution is stirred at rt for 2 h before it is concentrated, diluted with DCM (20 mL) and washed with 2 N aq. HCl (10 mL). The aq. phase is extracted three times with DCM (3×20 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (105 mg) as a white solid; LC-MS: tR=1.14 min, [M+H]+=523.21; 1H NMR (CD3OD): δ 7.82 (s, 1H), 7.79 (s, 1H), 7.49 (s, 1H), 7.23 (s, 1H), 3.99 (s, 3H), 3.92 (t, J=6.2 Hz, 2H), 3.52 (t, J=6.9 Hz, 2H), 3.31 (s, 2H), 3.22-3.31 (m, 1H), 2.75 (q, J=7.5 Hz, 2H), 2.36 (s, 3H), 2.04-2.15 (m, 4H), 1.85-1.95 (m, 4H), 1.73-1.82 (m, 2H), 1.29 (t, J=7.5 Hz, 3H).

Provenance & Evidence