Acetone → (4-((1,1-Dioxidothiomorpholino)methyl)phenyl)boronic acid

Participants

Reaction Conditions

Reaction Steps

A suspension of (4-bromomethylphenyl)boronic acid (2.00 g, 9.31 mmol), thiomorpholine 1,1-dioxide (1.50 g, 11.1 mmol) and potassium carbonate (2.60 g, 18.8 mmol) in acetone (25 mL, 340 mmol) was heated at 40° C. for 18 hours then cooled to room temperature. The volatiles were evaporated and the residue was suspended in saturated aqueous ammonium chloride (100 mL). The aqueous was decanted from the waxy solid and the solid was dissolved in methanol (50 mL), filtered to remove insoluble salts and evaporated. 4-[(4-boronophenyl)methyl]-thiomorpholine 1,1-dioxide was isolated as a tan foam. The crude material was used without further purification. 70b) 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine was prepared from 5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine and 4-[(4-boronophenyl)methyl]-thiomorpholine 1,1-dioxide in a manner analogous to Step 2c. The reaction product was taken on to the next step. 70c) 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-N-[4-(4-methylpiperazin-1-yl)phenyl][1,2,4]triazolo[1,5-a]pyridin-2-amine was prepared from 5-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-amine (75.0 mg, 0.210 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (65.0 mg, 0.255 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (22.0 mg, 0.0402 mmol) as the ligand in a manner analogous to Step 2d. The title compound was isolated as a yellow foam (0.045 g, 40%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.00 (d, J=7.0 Hz, 2H), 7.52-7.43 (m, 6H), 6.98-6.91 (m, 3H), 6.67 (s, 1H), 3.76 (s, 2H), 3.18-3.03 (m, 12H), 2.62-2.56 (m, 4H), 2.36 (s, 3H). MS=532 (MH)+.

Provenance & Evidence