合成路线1

Vanillic acid (I) is condensed with 1-(3-chloropropyl)pyrrolidine (II) by means of K2CO3 and KI in hot DMF yielding 3-methoxy-4-[3-(1-pyrrolidinyl)propoxy]benzoic acid (III), which is nitrated with fuming HNO3 in TFA to afford the ortho-nitrobenzoic acid (IV). Subsequent chlorination of acid (IV) with SOCl2, followed by reaction with ammonia in THF/CH2Cl2, leads to the corresponding benzamide (V), which is reduced at the nitro group by means of Fe/HCl, providing the expected ortho-aminobenzoic acid (VI). The cyclization of (VI) with Gold’s reagent (VII) in dioxane gives the quinazolinone (VIII), which is converted to the 4-chloroquinazoline (IX) upon treatment with SOCl2 in the presence of a catalytic amount of DMF. Cediranib is finally obtained by condensation of chloroquinazoline (IX) with 4-fluoro-5-hydroxy-2-methylindole (X) in the presence of K2CO3 in hot DMF (1, 2). Scheme 1.