2,2-Dimethylpropionic acid 2-[(S)-3-(5-fluoro-2-{(S)-2-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]propionylamino}phenylamino)piperidin-1-yl]ethyl ester → HCID 178461946, compound

Participants

Reaction Steps

A solution of 2,2-dimethylpropionic acid 2-[(S)-3-(5-fluoro-2-{(S)-2-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]propionylamino}phenylamino)piperidin-1-yl]ethyl ester (583 mg, 0.95 mmol), in aqueous 6M HCl (20 mL) was refluxed for 30 min. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue 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. The fractions containing product were purified by column chromatography (C18, gradient 2-40% MeOH in 0.5% TFA/H2O) then loaded in dioxane onto an Isolute® SCX-2 cartridge. The cartridge was washed with dioxane then the product eluted with 10% 880 NH3 in dioxane. Further purification by column chromatography (Si—PCC, gradient 3-21% 2M NH3/MeOH in DCM) afforded 278 as a colourless solid (85.8 mg, 21%). LCMS (Method K): RT 2.05 min [M+H]+ 425.1. 1H NMR (CD3OD, 400 MHz): δ 8.29 (1H, s), 8.09 (1H, s), 7.58 (1H, dd, J=9.0, 5.0 Hz), 7.50 (1H, dd, J=9.6, 2.3 Hz), 7.00 (1H, dt, J=9.3, 2.3 Hz), 5.97 (1H, bs), 4.80-4.71 (1H, m), 3.41-3.39 (2H, m), 3.15-3.10 (1H, m), 2.92 (1H, bd, J=11.3 Hz), 2.81 (1H, t, J=11.0 Hz), 2.53-2.21 (4H, m), 2.01-1.97 (1H, m), 1.92-1.86 (1H, m), 1.80 (3H, d, J=6.9 Hz), 1.78-1.70 (1H, m)

Provenance & Evidence