Tetrahydrofuran → 4-(5-((1,1-dioxidohexahydro-5H-isothiazolo[2,3-a]pyrazin-5-yl)methyl)-2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of hexahydro-2H-isothiazolo[2,3-a]pyrazine 1,1-dioxide (ref: WO2007028654, 0.180 g, 1.021 mmol) in THF (2.50 mL, 30.5 mmol) was added 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (preparation previously described, 0.3042 g, 0.511 mmol) and titanium (IV) ethoxide (0.529 mL, 2.55 mmol) and the mixture was heated at 70° C. overnight. The resulting mixture was cooled to 0° C. and excess sodium cyanoborohydride (0.160 g, 2.55 mmol) was added and the entire mixture was stirred at the same temperature for 1 h prior to being quenched with MeOH (1.0 mL). The mixture was concentrated and adsorbed onto a plug of silica gel and chromatographed through a silica gel column (100% DCM to 70% ethyl acetate in DCM to obtain the desired product 4-(5-((1,1-dioxidohexahydro-5H-isothiazolo[2,3-a]pyrazin-5-yl)methyl)-2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.297 g, 77%) as a yellow syrup. m/z (ESI, +ve ion) 756 (M+H)+.

Provenance & Evidence