Lenvatinib Impurity d synthesis

Yield:417717-04-5 66%

Steps:

69.C Step C:

Step C:
4-(3-chloro-4-(3-cyclopropylurea)phenoxy)-7-hydroxyquinoline-6-carboxamide
Under ice bath, to 4-[3-chloro-4-(cyclopropylamino carbonyl)aminophenoxy]-7-methoxy-6-quinolinecarboxamide (1.39g, 3.37mmol) in DCM ( 30mL) was added BBr3 (5mL, 52mmol).
after the addition, the reaction was kept under ice bath for 5 hours.
The solvent was distilled off under reduced pressure, and the reaction solution was washed with saturated sodium bicarbonate aqueous solution (100mL*2), and the organic phase was washed with saturated brine once.
Dry with sodium sulfate, concentrate under reduced pressure, and purify by silica gel column chromatography to afford the product (0.89g, 66%).

References:

EP3950677,2022,A1