4-Bromo-2-fluoroaniline (I) was protected as the N-Boc derivative (II) upon treatment with di-tert-butyl dicarbonate. Subsequent palladium-catalyzed bromide displacement in (II) with bis-pinacolatodiborane (III) furnished the arylboronate derivative (IV). The (dioxaspirodecyl)pyrimidine (VII) was prepared by coupling between 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (V) and 4-hydroxycyclohexanone ethylene ketal (VI) under Mitsunobu conditions. Subsequent Suzuki coupling of iodopyrrolopyrimidine (VII) with boronate (IV) afforded adduct (VIII). Displacement of the 4-chloro of (VIII) with simultaneous N-Boc group cleavage with ammonium hydroxide in dioxan at 120 C in a sealed vessel furnished the diamino compound (IX).

Acid hydrolysis of the ethylene ketal function of (IX) afforded ketone (X). This was subjected to a reductive amination with N-methylpiperazine (XI) in the presence of sodium triacetoxyborohydride to produce the corresponding disubstituted cyclohexane compound as a 3:1 mixture of cis- and trans-isomers. The desired trans-compound (XII) was then isolated by column chromatography. Finally, acylation of (XII) with 2,3-dichlorobenzenesulfonyl chloride (XIII) provided the title sulfonamide.

4-Bromo-2-fluoroaniline (I) was protected as the N-Boc derivative (II) upon treatment with di-tert-butyl dicarbonate. Subsequent palladium-catalyzed bromide displacement in (II) with bis-pinacolatodiborane (III) furnished the arylboronate derivative (IV). The (dioxaspirodecyl)pyrimidine (VII) was prepared by coupling between 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (V) and 4-hydroxycyclohexanone ethylene ketal (VI) under Mitsunobu conditions. Subsequent Suzuki coupling of iodopyrrolopyrimidine (VII) with boronate (IV) afforded adduct (VIII). Displacement of the 4-chloro of (VIII) with simultaneous N-Boc group cleavage with ammonium hydroxide in dioxan at 120 C in a sealed vessel furnished the diamino compound (IX).

Acid hydrolysis of the ethylene ketal function of (IX) afforded ketone (X). This was subjected to a reductive amination with N-methylpiperazine (XI) in the presence of sodium triacetoxyborohydride to produce the corresponding disubstituted cyclohexane compound as a 3:1 mixture of cis- and trans-isomers. The desired trans-compound (XII) was then isolated by column chromatography. Finally, acylation of (XII) with 2,3-dichlorobenzenesulfonyl chloride (XIII) provided the title sulfonamide.

4-Bromo-2-fluoroaniline (I) was protected as the N-Boc derivative (II) upon treatment with di-tert-butyl dicarbonate. Subsequent palladium-catalyzed bromide displacement in (II) with bis-pinacolatodiborane (III) furnished the arylboronate derivative (IV). The (dioxaspirodecyl)pyrimidine (VII) was prepared by coupling between 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (V) and 4-hydroxycyclohexanone ethylene ketal (VI) under Mitsunobu conditions. Subsequent Suzuki coupling of iodopyrrolopyrimidine (VII) with boronate (IV) afforded adduct (VIII). Displacement of the 4-chloro of (VIII) with simultaneous N-Boc group cleavage with ammonium hydroxide in dioxan at 120 C in a sealed vessel furnished the diamino compound (IX).

Acid hydrolysis of the ethylene ketal function of (IX) afforded ketone (X). This was subjected to a reductive amination with N-methylpiperazine (XI) in the presence of sodium triacetoxyborohydride to produce the corresponding disubstituted cyclohexane compound as a 3:1 mixture of cis- and trans-isomers. The desired trans-compound (XII) was then isolated by column chromatography. Finally, acylation of (XII) with 2,3-dichlorobenzenesulfonyl chloride (XIII) provided the title sulfonamide.