合成路线1

Treatment of methyl 4-chloroanthranilate (I) with iodine and silver sulfate afforded the 5-iodinated derivative (II). The amino group of (II) was then protected by acylation with acetyl chloride to give amide (III). Carbonylation of the aryl iodide (III) with palladium catalyst under CO atmosphere in DMF/MeOH provided the isophthalate diester (IV). Acid hydrolysis of the acetamido group of (IV), followed by acylation of the resultant amine (V) with 3,4,5-trimethylphenylacetyl chloride, (VI) furnished amide (VII). Quinolone (VIII) was then formed by cyclization of (VII) under basic conditions. Subsequent Mitsunobu coupling of (VIII) with (S)-N-Boc-2-(2-hydroxyethyl)azetidine (IX) provided ether (X). After hydrolysis of the methyl ester of (X) with LiOH, the resulting acid (XI) was coupled with 4-aminopyrimidine (XII) in the presence of EDC to give amide (XIII). The N-Boc group of (XIII) was then deprotected by treatment with trifluoroacetic acid, and the title compound was isolated after conversion to the dihydrochloride salt.