Isobutyl chloroformate → HCID 131727831, compound

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Reaction Steps

To a solution of 300 mg of the compound of Example 16 in 6 ml of THF, 56 μl of N-methylmorpholine were added, 60 μl of isobutyl chloroformate was added at −15° C., and the mixture was stirred for 1.5 hours. And, to a solution of 96 mg of methanesulfonamide in 4 ml of THF, 348 μl of 1,8-diazabicyclo[5,4,0]-7-undecene was added, and the mixture was stirred at room temperature for 19 hours and at 50° C. for 2 days. The reaction solution was mixed with saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was washed with brine and dried over sodium sulfate. The residue obtained by the evaporation of the solvent under reduced pressure was purified by silica gel column chromatography (hexane-THF=2:1˜0:1) and then by silica gel column chromatography (chloroform-MeOH=100:0˜100:3), and the obtained compound was dissolved in chloroform-EtOH. A 0.1M HCl-EtOAc solution was added thereto, the solvent was evaporated under reduced pressure, EtOH-diethylether was added thereto, and the thus-produced precipitate was collected by filtration to obtain 30 mg of 5-chloro-N-[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]-6-(4-(3-[2-(methanesulfonylimino)azepin-1-yl]propylaminocarbonyl)piperidin-1-yl)nicotinamide hydrochloride.

Provenance & Evidence