Water → 6-((R)-2-hydroxy-propoxy)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-4-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide

Participants

Reaction Steps

To a stirred mixture of 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-4-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide (80 mg) and (R)-2-(tetrahydro-pyran-2-yloxy)-propan-1-ol (100 μL) in dry DMF (1 mL) was added NaH (40 mg, dispersion in mineral oil) and the mixture was stirred at room temperature for 1 h. Then, water (10 mL) was added and the reaction mixture stirred for 10 minutes. The precipitated solid was filtered and dissolved in 1:1 mixture of methanol and DCM (5 mL). To this was added 2 M solution of hydrochloric acid in methanol (1 mL) and stirred at room temperature for 2 h. After air drying, the product was purified by column chromatography (12 g pre-packed silica gel column cartridge) using DCM and 2N ammonia in methanol to afford 6-((R)-2-hydroxy-propoxy)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-4-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide (37 mg). LCMS (m/z): 532. 1H NMR (400 MHz, DMSO-d6): δ 12.5 and 11.5 (1H, brs) 8.85 (1H, s) 8.15 (1H, d) 7.92 (1H, brs) 7.87-7.93 (3H, m) 7.55-7.63 (2H, m) 7.08 (1H, d) 5.01 (1H, d) 4.17 (2H, d) 4.03-4.07 (1H, m) 1.18 (3H, d).

Provenance & Evidence