2-Oxopropanethioamide → 6'-(3-Fluoropropoxy)-4-hydroxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

Participants

Reaction Conditions

Reaction Steps

To N-(5′-(3-fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2′-indene]-3′(1′H)-ylidene)-2-methylpropane-2-sulfinamide (Intermediate 32, 275 mg, 0.70 mmol) in dioxane (1 mL) under an atmosphere of nitrogen was added HCl (4 M in 1,4-dioxane, 1.74 mL, 6.95 mmol). The mixture was stirred at r.t. for 2 h and was then concentrated. DCM (1-2 mL) and Et2O was added and a solid was formed. The solid was filtered off and washed with diethylether. The solid was dissolved in DCM. Sat. aq. NaHCO3 was added and mixture was poured in to a phase separator. The organic phase was collected and concentrated to give 6′-(3-fluoropropoxy)-1′-imino-1′,3′-dihydrospiro[cyclohexane-1,2′-inden]-4-ol (227 mg). The obtained imine was mixed with 2-oxopropanethioamide (Intermediate 1, 239 mg, 2.32 mmol) in dry MeOH (4 mL) and the resulting orange solution was heated at 60° C. under an atmosphere of nitrogen overnight. The mixture was allowed to cool to r.t., and concentrated. The residue was purified by flash column chromatography using a gradient of 0-100% EtOAc in heptane, providing 104 mg (36% yield) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.04-1.21 (m, 4 H) 1.41-1.48 (m, 2 H) 1.66-1.73 (m, 2 H) 2.02 (t, 1 H) 2.07 (quin, 1 H) 2.26 (s, 3 H) 2.93 (d, 1 H) 3.01 (d, 1 H) 3.22-3.29 (m, 1 H) 3.97 (tq, 2 H) 4.52 (t, 1 H) 4.55 (d, 1 H) 4.62 (t, 1 H) 6.32 (d, 1 H) 6.89 (dd, 1 H) 7.26 (d, 1 H) 12.28 (s, 1 H); MS (ES+) m/z 377.07 [M+H]+.

Provenance & Evidence