N,N-Dimethyl-1,3-propanediamine → 2-[5-(4-Benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-isobutyl-4-methoxy-pyridine

Participants

Reaction Steps

To a solution of 6-isobutyl-4-methoxy-pyridine-2-carboxylic acid (270 mg, 1.10 mmol), 4-benzyloxy-3,5-dimethyl-benzoic acid hydrazide (327 mg, 1.21 mmol) and DIPEA (455 mg, 3.52 mmol) in DCM (15 mL), PyBOP (858 mg, 1.65 mmol) is added at 0° C. The mixture is stirred for 30 min at rt, the reaction is diluted with diethyl ether and washed with 1 N aq. NaOH solution followed by 1 M aq. NaH2PO4 solution. The org. extract is dried over Na2SO4, filtered and concentrated to give the crude hydrazide intermediate; LC-MS: tR=1.00 min, [M+H]+=462.23. This material (1.13 g) is dissolved in DCM (15 mL) and pyridine (1 mL) and the mixture is cooled to 0° C. before trifluoromethanesulfonic anhydride (1.38 g, 4.89 mmol) is added dropwise. The mixture is warmed to rt and stirring is continued for 16 h. The reaction is quenched by adding 3-dimethylamino-1-propylamine (50 mg, 0.49 mmol). The mixture is washed twice with 1 N aq. NaH2PO4 solution followed by water, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-[5-(4-benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-isobutyl-4-methoxy-pyridine (414 mg) as a yellow oil; LC-MS: tR=1.15 min, [M+H]+=444.21.

Provenance & Evidence