4-Methylbenzoyl Chloride → HCID 11377053, compound

Participants

Reaction Steps

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath was charged with 16.0 g of {3-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-propyl}carbamic acid tert-butyl ester (the compound of Formula 302 prepared, e.g., as described in Example 1.7 or 3.2), 80 mL of DCM and 9.1 g (12 mL) (2.2 eq) of DIPEA and stirred until dissolved. To the stirring solution, p-toluoyl chloride 5.5 g (4.7 mL) (1.1 eq) was added and stirring continued for approximately 6 hours until the reaction was determined to be completed by TLC (hexanes/ethyl acetate 1:1). The reaction was quenched with methanol (5 mL) and stirred for an additional 30 minutes, then cooled followed by addition of 1N hydrochloric acid (exothermic) to wash until acidic. The resulting solution was dried over sodium sulfate, the solvents stripped under vacuum at 30–40° C. The crude product thus obtained was purified on a silica gel column (eluted with 15% ethyl acetate in hexanes) and concentrated to give the title compound of Formula 304 {3-[[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propyl]-(4-methyl-benzoyl)-amino]-propyl}-carbamic acid tert-butyl ester as an off-white foam solid, 10.8 g (60% yield).

Provenance & Evidence