反应详情

To a 40 mL screw-cap vial was added tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamate 43 (2.53 g, 7.35 mmol) followed by methanol (7 mL), then HCl in dioxane (4 mol/L, 7.5 equiv., 55.1 mmol, 13.8 mL). The reaction was stirred at room temperature for 2 hours. Resulting precipitate was collected by filtration, and washed 2× with ethyl acetate, yielding 1.93 g of product as an orange solid, 3×HCl salt. 25 mg was purified by reverse phase HPLC, yielding 5 mg of neutralized product. 1H NMR (400 MHz, DMSO) δ 8.17-8.13 (s, 1H), 7.77-7.73 (d, J=9.3 Hz, 1H), 7.46-7.39 (d, J=9.4 Hz, 1H), 7.39-7.07 (s, 2H), 4.48-4.26 (m, 2H), 3.03-2.90 (m, 1H), 2.73-2.62 (m, 2H), 1.93-1.82 (m, 1H), 1.82-1.67 (m, 1H), 1.52-1.36 (m, 1H), 1.34-1.16 (m, 1H). LCMS M?Z (M+H)=245.

1. customTo a 40 mL screw-cap vial
2. customResulting precipitate
3. filtrationwas collected by filtration
4. washwashed 2× with ethyl acetate