1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57657244, compound

Participants

Reaction Steps

3-[4-Amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]propanoic acid (1.25 g, 3.30 mmol), anhydrous pyridine (75 mL) and 1-hydroxybenzotriazole (892 mg, 6.60 mmol) were combined and the reaction was stirred for 30 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (1.27 g, 6.60 mmol) was added and the reaction mixture was stirred for an additional 15 minutes. Thiomorpholine 1,1-dioxide (895 mg, 6.60 mmol) was added in one portion. After stirring for 18 hours the solution was concentrated under reduced pressure and the residual foam was dissolved in chloroform (50 mL) and washed with 1% aqueous sodium carbonate (2×25 mL). The combined aqueous washes were extracted with chloroform. The combined organic fractions were concentrated under reduced pressure and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-25% CMA over 1500 mL, followed by 25-30% CMA over 500 mL, finally 30% CMA over 1000 mL). The resulting material was subjected to a second chromatography purification using a HORIZON HPFC system (silica cartridge, eluting with CMA:chloroform gradient; 0-25% CMA over 1500 mL, followed by 25-30% CMA over 500 mL) followed by recrystallization from acetonitrile to provide 1.07 g of 1-[4-amino-7-[3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropyl]-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white solid, mp 190-192° C.

Provenance & Evidence