1,1'-Carbonyldiimidazole → HCID 67540189, compound

Participants

Reaction Steps

The PS-CDI (175 mg, 0.181 mmol), HOBt monohydrate (214 mg, 0.140 mmol), 4-piperazin-1-yl-quinazoline dihydrochloride (52 mg, 0.181 mmol), and 2-(2-tert-butoxycarbonylamino-ethoxy)-3-(4-chlorophenyl)-propionic acid (48 mg, 0.140 mmol; prepared by alkylation of (2-Boc-amino-ethoxy)-acetic acid ethyl ester with 4-chlorobenzylbromide according to procedures described in the literature: Nizal S. Chandrakumar et al. J. Med. Chem. 1992, 35, 2928-2938) were suspended/dissolved in 2.5 mL of chloroform (plus 3-5 drops THF). The mixture was shaken at room temperature overnight, then treated with MP-CO3 (330 mg, 0.838 mmol) for two hours. The mixture was vacuum filtered, rinsed with chloroform, and concentrated in vacuo. The residue was purified on silica gel (1:19 DCM:EtOAc) to afford 2-(2-Boc-amino-ethoxy)-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one. This material was dissolved in 1.0 mL of 1,4-dioxane and treated with 1.5 mL of 4M HCl in 1,4-dioxane affording slow precipitation. The mixture was sonicated briefly and stirred at room temperature overnight to completion. The resulting suspension was concentrated in vacuo, and the solids were suspended in diethyl ether, filtered under nitrogen pressure, and dried in vacuo to afford 2-(2-amino-ethoxy)-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one dihydrochloride as a yellow powder (13 mg, 18%). LCMS (APCI+) m/z 440 [M+H]+. HPLC R2=1.75 min.

Provenance & Evidence