反应详情

4-{[7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carbonyl]-aminooxy}-piperidine-1-carboxylic acid tert-butyl ester (180 mg, 0.30 mmol) was dissolved in hydrochloric acid in dioxane (1 mL, 4M). The reaction was stirred at room temperature for 30 minutes then concentrated in vacuo. The resultant residue was subject to reverse phase HPLC (gradient 10-60% acetonitrile/water 0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm). The product was dissolved in ethyl acetate (5 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo to yield the title compound as a yellow solid (37 mg, 25%). 1H NMR (DMSO-d6): 8.73 (1H, s), 7.92 (1H, s), 7.49 (1H, dd, J=10.98, 1.92 Hz), 7.41-7.38 (2H, m), 7.16-7.13 (1H, m), 6.72 (1H, d, J=0.92 Hz), 5.93 (1H, t, J=8.84 Hz), 3.72-3.62 (1H, m), 2.87 (2H, dt, J=12.72, 4.49 Hz), 2.41-2.31 (2H, m), 1.67 (2H, dt, J=12.84, 4.01 Hz), 1.32-1.21 (2H, m). LCMS (Method A): RT=6.17 min, M+H+=496.

1. concentrationthen concentrated in vacuo
2. dissolutionThe product was dissolved in ethyl acetate (5 mL)
3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
5. washThe combined organic fractions were washed with brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo