反应详情

温度

45 °C

To a suspension of 5-(2-fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amide (58.36 g, 0.12 mol) in methanol (600 mL) was added aqueous hydrochloric acid (242 mL, 1M, 0.242 mol). The reaction mixture was stirred and warmed to 45° C. for 1 hr during which time the solids dissolved. The reaction mixture was then cooled to room temperature, and concentrated in vacuo to remove the methanol. The resultant residue was treated with aqueous saturated sodium hydrogen carbonate and stirred at room temperature for 1 hr before collecting crude product by filtration, and drying at 55° C. over phosphorus (V) oxide under vacuum for 24 hr. The crude product was crystallized from IPA:H2O (1:1, v/v) (800 mL) with slow cooling and mechanical stirring. The product was collected by filtration and washed cold IPA:H2O (1:1, v/v) (100 mL) before being dried in vacuo at 55° C. to yield the title compound as a light brown solid (50.2 g, 90%). LCMS (Method A): RT=5.58 min, [M+H]+=457. 1H NMR (DMSO-d6, 400 MHz) 8.05 (1 H, s), 7.58 (1 H, dd, J=10.69, 1.92 Hz), 7.43 (1 H, s), 7.39 (1 H, d, J=9.33 Hz), 7.31-7.28 (1 H, m), 6.89 (1 H, d, J=9.31 Hz), 6.34 (1 H, t, J=8.68 Hz), 4.64 (1 H, s), 3.64 (2 H, t; J=4.78 Hz), 3.46 (2 H, m).

1. dissolutiondissolved
2. temperatureThe reaction mixture was then cooled to room temperature
3. concentrationconcentrated in vacuo
4. customto remove the methanol
5. additionThe resultant residue was treated with aqueous saturated sodium hydrogen carbonate
6. stirringstirred at room temperature for 1 hr
7. custombefore collecting crude product
8. filtrationby filtration
9. dry with materialdrying at 55° C. over phosphorus (V) oxide under vacuum for 24 hr
10. customThe crude product was crystallized from IPA:H2O (1:1
11. temperaturev/v) (800 mL) with slow cooling
12. filtrationThe product was collected by filtration
13. washwashed cold IPA:H2O (1:1
14. customv/v) (100 mL) before being dried in vacuo at 55° C.