HCID 86711139, compound → HCID 136633865, compound

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyl (2-((3-(1-(2-(9-((tert-butyldimethylsilyl)oxy)-2-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-3-yl)ethyl)piperidin-4-yl)benzo[d]isoxazol-6-yl)oxy)ethyl)carbamate, prepared as described in the previous step, (70 mg, 0.103 mmol) in HCl/isopropanol (10 mL, 5 N) was stirred for 1 h at 60° C. The reaction mixture was evaporated at 40° C. under reduced pressure and dissolved carefully in aqueous saturated sodium bicarbonate solution (5 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under reduced pressure at 40° C. The aqueous layer still contained product, which was recovered by evaporating the aqueous layer to dryness at 40° C. under reduced pressure. The resulting residue from the aqueous layer was re-dissolved in water and brought over a conditioned Waters Oasis SPE (6 cc) column and afterwards eluted with methanol. The methanol elution fraction was combined with the residue of the dichloromethane extraction and evaporated to dryness at 40° C. under reduced pressure to yield the title compound along with a side product (ESI-MS (M+1) 468; side product being 5% 9-hydroxy-3-(2-(4-(6-hydroxybenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (M+1) 425). The mixture was used in the next step without additional purification.

Provenance & Evidence