合成路线1

In one strategy, 2,4-difluoroaniline (I) is lithiated with BuLi in the presence of 1,2-bis(chlorodimethylsilyl)ethane in THF at –78 °C, and subsequently acylated with benzyl chloroformate, yielding benzyl 3-amino-2,6-difluorobenzoate (II). N-Sulfonylation of aniline (II) with propane-1-sulfonyl chloride (III) using pyridine in CH2Cl2 gives the corresponding sulfonamide (IV), which is then debenzylated with H2 over Pd(OH)2/C in MeOH to provide the benzoic acid derivative (V). After chlorination of acid (V) with SOCl2 in refluxing toluene, the resulting acid chloride (VI) is subjected to Friedel–Crafts reaction with 5-bromopyrrolo[2,3-b]pyridine (VII) in the presence of AlCl3 in CH2Cl2 to afford ketone (VIII). Finally, the aryl bromide (VIII) is submitted to a Suzuki coupling with 4-chlorophenylboronic acid (IX) in the presence of Pd(PPh3)4 and K2CO3 in acetonitrile .
In an alternative strategy, 2,4-difluoroaniline (I) is coupled with propane-1-sulfonyl chloride (III) by means of Et3N in THF to give N-(2,4-difluorophenyl)propane-1-sulfonamide (X), which, after lithiation with LDA in THF, is formylated by reaction with DMF, yielding 2,6-difluoro-3-(propylsulfonamido)benzaldehyde (XI). Condensation of aldehyde (XI) with 5-(4-chlorophenyl)pyrrolo[2,3-b]pyridine (XII) (obtained by Suzuki coupling of 5-bromopyrrolo[2,3-b]pyridine (VII) with boronic acid (IX) in the presence of Pd(PPh3)4 and K2CO3 in acetonitrile/H2O) using KOH in MeOH provides a mixture of the diarylcarbinol (XIII) and its corresponding methyl ether, which is further enriched in the desired alcohol (XIII) by demethylation with HBr in AcOH. Alcohol (XIII) is finally oxidized using DDQ in dioxane .