Cyclohexanecarboxylic acid → HCID 86704199, compound

Participants

Reaction Steps

50 mg (0.39 mmol) of cyclohexanecarboxylic acid were dissolved in 3 mL of dry DCM and 56 μL (0.39 mmol) of TEA were added to the mixture. A solution of 33 μL of oxalyl chloride in 2 mL of DCM was then added dropwise at r.t. After 3 h the solvent was removed under reduced pressure, toluene was added several times and re-evaporated again. The residue was dissolved in 2 mL of dry DCM and dropped into a solution of 50 mg (0.095 mmol) of N-{3-[2-amino-5-(pyridin-4-yl)-1,3-thiazol-4-yl]-2,4-difluorophenyl}-2,5-difluoro-N-(methoxymethyl)benzenesulfonamide in 3 mL of the same solvent containing 56 μL of TEA. The reaction was maintained at r.t. overnight under stirring. The solution was then diluted with DCM and washed with aqueous NaHCO3. The organic layer was dried over Na2SO4 and evaporated, to give N-(cyclohexylcarbonyl)-N-[4-(3-{[(2,5-difluorophenyl)sulfonyl]-(methoxymethyl)amino}-2,6-difluorophenyl)-5-(pyridin-4-yl)-1,3-thiazol-2-yl]cyclohexanecarboxamide as an oil. The latter was taken up with 5 mL of MeOH and 1 mL of TEA was added to the resulting solution. The reaction was maintained at r. t. overnight. The solvent was then evaporated, the residue re-dissolved with DCM and washed with brine. The organic phase was dried over Na2SO4 and evaporated again, to afford N-[4-(3-{[(2,5-difluorophenyl)sulfonyl](methoxymethyl)-amino}-2,6-difluorophenyl)-5-(pyridin-4-yl)-1,3-thiazol-2-yl]cyclohexanecarboxamide. The latter was finally dissolved with 9 mL of TFA and 1 mL of water and heated at 75° C. for 6 h. The solvent was removed under reduced pressure, the residue re-dissolved with DCM and washed with aqueous NaHCO3. The organic layer was dried over Na2SO4 and evaporated. The crude was finally purified by flash chromatography on a silica gel precoated column, eluted with DCM-MeOH 98/2, yielding 35 mg (63% overall) of the title compound.

Provenance & Evidence