Hydrogen Peroxide → tert-butyl (1S,2R)-2-(5-carbamoyl-6-chloropyrazin-2-ylamino)cyclohexylcarbamate

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Reaction Conditions

Reaction Steps

Tert-butyl (1S,2R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)cyclohexylcarbamate (300 mg) was dissolved in 20 mL methanol and 10 mL DMSO. To it were added K2CO3 powder (300 mg) and then 3 mL H2O2 (50% solution). The mixture was stirred at 40° C. for 1 h. To it was poured 200 mL EtOAc. The mixture was then washed with water and brine. The organic phase was dried over MgSO4, concentrated in vacuo and pumped to dryness to afford tert-butyl (1S,2R)-2-(5-carbamoyl-6-chloropyrazin-2-ylamino)cyclohexylcarbamate in quantitative yield. Tert-butyl (1S,2R)-2-(5-carbamoyl-6-chloropyrazin-2-ylamino)cyclohexylcarbamate (60 mg, 0.16 mmol) was dissolved in 3 mL NMP. To it were added 4-aminoterahydropyran (100 mg, 0.96 mmol) and DIEA (55 μL, 0.32 mmol). The mixture was stirred at 100° C. for overnight in a sealed tube. It was cooled to RT, diluted with EtOAc, washed with sat. NH4Cl solution, dried over MgSO4, concentrated in vacuo to afford crude tert-butyl (1S,2R)-2-(5-carbamoyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrazin-2-ylamino)cyclohexylcarbamate. It was treated with 1:1 DCM and TFA at RT for 1.5 h. It was concentrated and subjected to reverse phase preparative HPLC to isolate the title compound as HCl salt (57 mg). MS found for C16H26N6O2 as (M+H)+ 335.5. UV: λ=282 nm.

Provenance & Evidence