Methyl 4-chloroanthranilate → 3-Benzyl-7-chloro-1-pyrrolidine-2-yl-2,3-dihydro-1H-quinazoline-4-one

Participants

Reaction Steps

Formula 103 where T is a covalent bond: W, X, Y and Z are —C═: U′—V′ is —N(R6′)—CReRf—; R1, R2, R4, and Ra to Rf are H: R3 is chloro; and R6′ is Boc A solution of pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (6.0 g, 28 mmol), 2-amino-4-chloro-benzoic acid methyl ester (4.6 g, 25 mmol), PyBroP (14.4 g, 31 mmol), diisopropylethylamine (6 mL) in pyridine (60 mL) was stirred overnight at room temperature, after which HPLC/MS showed complete conversion of starting material. The solvents were removed under vacuum and the residue partitioned between ethyl acetate (100 mL) and water (50 mL). The organic layer was washed with 1M HCl (50 mL) and saturated NaHCO3 (50 mL), dried over MgSO4, filtered, and concentrated under vacuum. Silica gel chromatography using 30% ethyl acetate/hexanes as eluent gave 9.3 g (87% yield) of the desired product of Formula 103, 2-(5-chloro-2-methoxycarbonyl-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, as a yellow foam. LRMS (MH+) m/z 383.

Provenance & Evidence