反应详情

温度

50 °C

2-(2-(Ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-yl)isoindoline-1,3-dione (1600 mg, 3.6 mmol), 1,3-dihydro-1,3-dioxo-2H-isoindole-2-acetic acid (CAN 4702-13-0, 2.22 g, 10.8 mmol) and 4-(1-pyrrolidinyl)-pyridine (800 mg, 5.4 mmol) were combined with DCM (36 mL) to give a white suspension. N,N′-diisopropylcarbodiimide (1.68 mL, 10.8 mmol) and molecular sieves were added. The reaction mixture was heated to 50° C. and stirred for 2 hours and was, after cooling, filtered. The filtrate was diluted with DCM (150 mL) and washed with 1 N hydrochloric acid and water. Water phases were extracted with DCM, organic phases were combined, dried over MgSO4, filtered and concentrated in vacuo. Diisopropylurea was removed after trituration with DCM/methanol by filtration, the filtrate was concentrated and the residue was purified by flash chromatography (silica gel, 0% to 100% ethyl acetate in heptane) to give a light yellow solid. Crystallization from DMSO yielded a first crop of product (1.95 g), and the mother liquor after concentration and preparative HPLC another 0.13 g of product. In total 2.08 g (91%) of the title compound was isolated as white solid; LC-MS (UV peak area, ESI) 95.9%, 632.2157 (MH+).

1. customto give a white suspension
2. temperatureafter cooling
3. filtrationfiltered
4. additionThe filtrate was diluted with DCM (150 mL)
5. washwashed with 1 N hydrochloric acid and water
6. extractionWater phases were extracted with DCM, organic phases
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customDiisopropylurea was removed after trituration with DCM/methanol
11. filtrationby filtration
12. concentrationthe filtrate was concentrated
13. customthe residue was purified by flash chromatography (silica gel, 0% to 100% ethyl acetate in heptane)
14. customto give a light yellow solid
15. customCrystallization from DMSO