Phosphorus oxychloride → 7-(Benzyloxy)-4-chloro-6-methoxyquinoline

Participants

Reaction Steps

7-Benzyloxy-6-methoxy-quinolin-4-ol (WO2006108059) (1 g) was refluxed with POCl3 (8 ml) for 3 hours. The reaction was evaporated and dissolved into DCM (80 ml) that was washed with ice water followed by brine. The organic layer was dried with Na2SO4 and evaporated to dryness to give a dark yellow solid as 4-chloro-7-benzyloxy-6-methoxy-quinoline that was mixed with 5-aminoindole (600 mg) in isopropanol (15 ml). The mixture was refluxed for one hour and cooled to RT and the precipitate was filtered to give the product as 4-(1H-indol-5-ylamino)-7-benzyloxy-6-methoxy-quinoline (710 mg). This product was mixed with Pd/C (10%, 100 mg) in EtOH (80 ml) and hydrogenated at 50 psi for 8 hours to give a gray suspension that was evaporated to dryness as 4-(1H-indol-5-ylamino)-7-hydroxy-6-methoxy-quinoline (˜85% purity) for next step without further purification.

Provenance & Evidence