Methyl iodide → Tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)carbamate

Temperatur

-78 °C

To a tetrahydrofuran (1 mL) solution of Compound 56 (72 mg), potassium bis(trimethylsilyl)amide (0.5M toluene solution: 273 μL) was added at −78° C. The mixture was stirred at −78° C. for 30 min and methyl iodide (9 μL) was added portionwise. The mixture was then stirred overnight as it was allowed to be slowly warmed to room temperature (20 to 30° C.). Subsequently, a saturated aqueous ammonium chloride solution was added to the reaction mixture and the mixture was extracted twice with chloroform. The organic layer was concentrated under reduced pressure and the resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (ethyl acetate: hexane=1: 19 to 1:1) to give 7.7 mg (10% yield) of tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)carbamate. 2.6 mg (42% yield) of the title compound was synthesized from tert-butyl 2-(1-((1-benzylpiperidine-4-yl)(methyl)-amino)-1-oxopropane-2-yloxy)-4,6-dimethylpyrimidine-5-yl(methyl)-carbamate in the same manner as in Example 71.

1. stirringThe mixture was then stirred overnight as it
2. temperatureto be slowly warmed to room temperature (20 to 30° C.)
3. extractionthe mixture was extracted twice with chloroform
4. concentrationThe organic layer was concentrated under reduced pressure
5. customthe resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (ethyl acetate: hexane=1: 19 to 1:1)

ORD-Eintrag

ord-47b01d6475354b19a04857c01d683f6e

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08685989B2