4-Toluenesulfonyl chloride → [5-(5-Ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Into each of three microwave vials is added {2-[N′-(5-ethyl-2-methyl-6-oxo-1,6-dihydro-pyridine-3-carbonyl)-hydrazino]-2-oxo-ethyl}-carbamic acid tert-butyl ester (190 mg, 0.519 mmol), tosyl chloride (119 mg, 0.624 mmol), and 2-t-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol/g, 1.18 g, 2.6 mmol) and anhydrous tetrahydrofuran (6 mL). Each vial is flushed with nitrogen, sealed and heated in the CEM Discover microwave at 145° C. holding at that temperature for 3 min, with a maximum pressure of 7.3 bar. LC/MS shows the reaction is complete. The product from all three vials are filtered and washed with THF. The filtrate is evaporated, and the residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1). Fractions containing the product are combined again and evaporated to give [5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-ylmethyl]-carbamic acid tert-butyl ester (329 mg, 61% yield). MS: m/e 719 (95%) (2M+Na), 249 (100%) (M+H); 1H NMR (CDCl3, δ, ppm): 7.87 (1H, s), 5.15 (1H, br.), 4.61 (2H, br.d), 4.00 (3H, s), 2.79 (3H, s), 2.60 (2H, q), 1.49 (9H, s), 1.21 (3H, t).

Provenance & Evidence