反应详情

A solution of 8-fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide (200 mg, 0.39 mmol) in methanol (1 mL) was loaded onto an SCX-2 column. The column was washed with methanol (10 mL) then the product was then eluted with ammonia in methanol (20 mL, 2M), the appropriate fractions were concentrated in vacuo. The resultant residue was subjected to reverse phase preparative HPLC (10-90% acetonitrile/water 0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm). The resultant product was dissolved in ethyl acetate (5 mL) and washed with aqueous saturated sodium bicarbonate solution (10 mL). The aqueous fraction was extracted twice with ethyl acetate (2×10 mL) and the combined organics were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo to yield the title compound as a white solid (88 mg, 39%). LCMS (Method A): RT=7.71 min, [M+H]+=475. 1H NMR (DMSO-d6): 8.20 (1 H, s), 7.60 (1 H, s), 7.57 (1 H, dd, J=10.73, 1.96 Hz), 7.26 (1 H, dd, J=8.43, 1.82 Hz), 6.82 (1 H, d, J=11.14 Hz), 6.30 (1 H, t, J=8.71 Hz), 3.65 (2 H, t, J=4.77 Hz), 3.45 (2 H, t, J=4.68 Hz).

1. washThe column was washed with methanol (10 mL)
2. washthe product was then eluted with ammonia in methanol (20 mL, 2M)
3. concentrationthe appropriate fractions were concentrated in vacuo
4. dissolutionThe resultant product was dissolved in ethyl acetate (5 mL)
5. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
6. extractionThe aqueous fraction was extracted twice with ethyl acetate (2×10 mL)
7. washthe combined organics were washed with brine (20 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo