Diisopropylethylamine → HCID 67460072, compound

Participants

Reaction Steps

To a mixture of methyl 5-(fluorocarbonyl)-3-phenylisoxazole-4-carboxylate (99 mg, 0.397 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (121 mg, 0.397 mmol) in acetonitrile (2 mL) at rt was added diisopropylethylamine (0.083 mL, 0.477 mmol) and the reaction mixture was allowed to stir at rt over the weekend. The reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL). The organic layer was washed with brine (20 mL), dried (MgSO4) and concentrated to afford a white solid that was chromatographed on a 12 gm Isco silica gel cartridge, eluting with a 0-100% EtOAc/Hex gradient. The essentially pure fractions containing product were concentrated to afford methyl 5-(3-(4-((3-(tert-butoxycarbonyl)azetidin-1-yl)methyl)phenyl)-1,2,4-oxadiazol-5-yl)-3-phenylisoxazole-4-carboxylate (128 mg, 0.248 mmol, 62.4% yield) as a white solid. HPLC retention time=1.78 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient. MS: (M+H)=517.22. 1H NMR (400 MHz, chloroform-d) d ppm 1.45 (s, 9H) 3.23-3.32 (m, 3H) 3.51-3.58 (m, 2H) 3.68 (s, 2H) 3.95 (s, 3H) 7.44 (d, J=8.0 Hz, 2H) 7.48-7.56 (m, 3H) 7.75 (dd, J=7.91, 1.63 Hz, 2H) 8.11 (d, J=8.3 Hz, 2H).

Provenance & Evidence