Sodium Hydroxide → 1-((2S)-3-{4-[5-(5-Diethylaminomethyl-4-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-azetidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of azetidine-2-carboxylic acid methyl ester hydrochloride (51 mg, 340 μmol) in methanol (1 mL), a solution of diethyl-{5-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-thiophen-2-ylmethyl}-amine (30 mg, 68 μmol) in methanol (1 mL) followed by DIPEA (90 mg, 679 μmol) is added. The mixture is stirred at 70° C. for 22 h before it is cooled to rt and 3 M aq. NaOH (0.35 mL) is added. The mixture is stirred at rt for 18 h before it is separated by prep. HPLC (Waters XBridge Prep C18, 75×30 mm ID, 10 μm, eluting with a gradient of acetonitrile in water containing 0.5% of sat. aq. ammonia) to give the title compound (29 mg) as a resin; LC-MS*: tR=0.74 min; [M+1]+=543.09; 1H NMR (D6-DMSO): δ1.03 (t, J=7.0 Hz, 6H), 1.21 (t, J=7.5 Hz, 3H), 2.22 (s, 3H), 2.33 (s, 3H), 2.58 (q, J=7.0 Hz, 4H), 2.62-2.69 (m, 1H), 2.73 (q, J=7.3 Hz, 2H), 3.10-3.17 (m, 1H), 3.18-3.22 (m, 1H), 3.22-3.28 (m, 2H), 3.42-3.51 (m, 2H), 3.66-3.72 (m, 1H), 3.73 (s, 2H), 3.74-3.80 (m, 2H), 7.72 (s, 2H), 7.80 (s, 1H).

Provenance & Evidence