Diisopropylcarbodiimide → 1-(4-(1,3-Dioxoisoindolin-2-yl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yl 2-(1,3-dioxoisoindolin-2-yl)acetate

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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+).

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