Tetrahydrofuran → HCID 178476647, compound

Participants

Reaction Steps

20 mg (0.055 mmol) [1,1′-bis-(diphenylphosphino)-ferrocene]palladium(II) chloride-methylene chloride was placed in 10 mL tetrahydrofuran, and the solution was deoxygenated with nitrogen. 0.200 g (0.523 mmol) N-(5-iodopyridin-2-yl)-N′-(2-methoxybenzyl)guanidine dissolved in 5 mL tetrahydrofuran was added dropwise through a septum (syringe technique), and the mixture was stirred for an additional 10 min. 4.19 mL (2.093 mmol) of a benzyl zinc bromide solution (0.5 M in tetrahydrofuran) was added dropwise under a nitrogen atmosphere. The reaction mixture was then heated under reflux for 4 hr. Since very little of the desired product was obtained, an additional 2.6 mL (1.308 mmol) of the benzyl zinc bromide solution was added. After additional heating under reflux for 4 hr the reaction went to completion. The reaction mixture was taken up in dichloromethane, and was extracted with saturated ammonium chloride solution (3×20 mL) and then with saturated sodium chloride solution (2×20 mL). The organic phase was dried over sodium sulfate and filtered, and the solvent was removed under vacuum. The residue was dissolved in acetonitrile/water (1:1) and 0.5 mL acetic acid, and purified via preparative HPLC (Waters, XTerra RP-18, eluent: water/acetonitrile/0.1 M acetic acid, with a flow rate of 30 mL/min and with gradients of 10% to 30% of the acetonitrile fraction in 20 min). The fractions containing pure product were combined and lyophilized with freeze drying, resulting in 0.072 g (1.771 mmol, 34%) N-(5-benzylpyridin-2-yl)-N′-(2-methoxybenzyl)guanidine in the form of the acetate salt (base/acetate in a ratio of 1:1).

Provenance & Evidence