Lithium hydroxide, monohydrate → HCID 11713302, compound

Participants

Reaction Steps

4-{[(4-Chloro-benzenesulfonyl)-(5-isopropyl-2-oxo-azepan-3-yl)-amino]-methyl}-benzoic acid methyl ester (0.30 g, 0.60 mmol) was saponified to the acid using LiOH.H2O (0.04 g, 0.90 mmol). The acid (0.10 g, 0.21 mmol) was dissolved in THF (3 ml) and added dropwise to a solution of 1,1-carbonyl diimidazole (CDI, 0.04 g, 0.23 mmol) in THF (0.5 ml). After 30 min, N-hydroxy-acetamidine (0.04 g, 0.23 mmol) was added. A further two equivalents each of CDI and N-hydroxy-acetamidine were added during a further 48 h stirring at r.t. The reaction mixture was concentrated and crude, coupled amidine was purified over silica gel (gradient ethyl acetate to ethyl acetate/methanol 15%): white solid 0.09 g (73%); MS: m/e=535.5 (MH+). Purified amidine (0.08 g, 0.15 mmol) cyclised in the presence of tetrabutylammonium fluoride (1 M, THF 5 ml) over 36 h at r.t. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organice extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The concentrated, crude product was purified using preparative RP(C18) chromatography: lyophilisate 15 mg; MS: m/e=517.4 (MH+).

Provenance & Evidence