Dimethylformamide → 5-(1-Phenylcyclopropyl)-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)thiazolo[5,4-b]pyridine

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Reaction Conditions

Reaction Steps

DMF (27.8 μL, 0.358 mmol) was added to a solution of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (198.6 mg, 0.716 mmol) and oxalyl chloride (66 μL, 0.757 mmol) in DCM (7.0 mL), and the resulting mixture was stirred at 25° C. for 4 h. The reaction mixture was then concentrated in vacuo and 3-amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione (175 mg, 0.720 mmol) was added. The resulting mixture was taken up in toluene (7.0 mL) and stirred at 25° C. for 5 min then at 100° C. for 1.5 h. (±)-10-camphorsulfonic acid (184 mg, 0.792 mmol) was then added, and the resulting mixture was heated at 100° C. for 1.5 h. The reaction mixture was subsequently cooled to 25° C. and purified by column chromatography (silica gel, 0-10% MeOH/DCM) to provide crude product, which was taken up in DCM (100 mL) and sequentially washed with sat. aq. NaHCO3 and brine. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 5-(1-phenylcyclopropyl)-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)thiazolo[5,4-b]pyridine as a light yellow solid. MS (ESI) m/z: Calculated: 383.1; Observed: 384.1 (M++1).

Provenance & Evidence