Hydrochloric Acid → HCID 178502279, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (2.66 g, 3.94 mmol, Example 7, Step 1) in MeOH (17 mL) was added aqueous concentrated HCl (1.97 mL, 23.65 mmol) and the resulting reaction was stirred at 60° C. for 1 hour. The reaction was allowed to cool to room temperature and concentrated in vacuo to give 2.28 g of crude residue. This material was then suspended in 1:1 THF-water (100 mL) followed by the addition of NaHCO3 (1.66 g, 19.70 mmol). The mixture was cooled to 5° C. and methyl chloroformate (1.0 M in THF, 4.33 mL, 4.33 mmol) was added dropwise. After 50 minutes, an additional charge of methyl chloroformate (1.0 M in THF, 4.33 mL, 4.33 mmol) was added and the reaction maintained for 45 minutes at 0° C. The reaction was quenched with water (300 mL) and the resulting layers were separated. The aqueous phase was extracted with EtOAc (2×200 mL) and the combined organic portions were washed with brine (2×400 mL), dried (Na2SO4), and concentrated. The resulting residue was triturated with 1:4 EtOAc-hexanes (10 mL) and washed with ether to provide 958 mg of (S)-methyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate: LCMS(m/z) 411.0 (MH+), tR=0.65 minute.

Provenance & Evidence