反应详情

A solution of 2,2-dimethylpropionic acid 2-[(R)-3-(5-fluoro-2-{(S)-2-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]butyrylamino}phenylamino)piperidin-1-yl]ethyl ester (258 mg, 0.41 mmol), in aqueous 6M HCl (3 mL) was refluxed for 40 min. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (C18, gradient 2-30% MeOH in 0.5% TFA/H2O) then loaded in dioxane/water (1:1) onto an Isolute® SCX-2 cartridge. The cartridge was washed with dioxane/water (1:1), then dioxane and the product eluted with 10% 880 NH3 in dioxane, then 2M NH3/MeOH. Further purification by column chromatography (Si—PCC, gradient 3-21% 2M NH3/MeOH in DCM) afforded a colourless solid. The preparation was repeated on the same scale to give a combined yield of 44.4 mg of 259 (12%). LCMS (Method K): RT 2.07 min [M+H]+ 439.1. 1H NMR (CD3OD, 400 MHz): δ 8.28 (1H, s), 8.09 (1H, s), 7.59 (1H, dd, J=8.9, 5.0 Hz), 7.50 (1H, dd, J=9.6, 2.3 Hz), 7.00 (1H, dt, J=9.2, 2.3 Hz), 5.84 (1H, bs), 5.04-4.94 (1H, m), 3.68 (2H, t, J=5.8 Hz), 3.12-3.08 (1H, m), 3.00-2.93 (2H, m), 2.71-2.57 (2H, m), 2.33-2.16 (4H, m), 1.89-1.86 (1H, m), 1.82-1.77 (1H, m), 1.62-1.51 (1H, m), 1.09 (3H, t, J=7.4 Hz)

1. customvolatiles were removed under reduced pressure
2. customthe resulting residue purified by column chromatography (C18, gradient 2-30% MeOH in 0.5% TFA/H2O)
3. washThe cartridge was washed with dioxane/water (1:1)
4. washdioxane and the product eluted with 10% 880 NH3 in dioxane
5. customFurther purification by column chromatography (Si—PCC, gradient 3-21% 2M NH3/MeOH in DCM)
6. customafforded a colourless solid