2-Chloro-N,N-dimethylethylamine → HCID 14773544, compound

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Reaction Steps

To a stirred, chilled (-78° C.) solution of (±) -3-methoxy-4-phenyl-1,3,4,5-tetrahydro-2H-1,3-benzodiazepine-2-one (5.0 g, 0.019 mol) of Example 1c and tetrahydrofuran (200 ml) was added n-butyllithium (9.1 ml of a 2.5 M solution in hexanes, 0.023 mol) (nitrogen atmosphere). The solution was stirred and cooled for 50 minutes, then 2-dimethylaminoethylchloride (10.22 .g, 0.095 mol) was added and the solution was allowed to warm to room temperature. The mixture was stirred and heated to 45° C. for 48 hours, with additional 2-dimethylaminoethylchloride added as follows: 16.5 hours, 14.0 g, 0.13 mol; 24 hours, 14.0 g, 0.13 mol. The mixture was then heated to reflux for 2 hours, allowed to cool, and water (400 ml) was added to quench the reaction. The tetrahydrofuran was removed in vacuo and the resulting oily aqueous phase was extracted twice with 250 ml portions of dichloromethane. The combined organic phase was washed twice with water (300 ml portions), once with saturated sodium chloride (200 ml), and was dried (Na2SO4), filtered, and concentrated to give a solid (10.45 g). The solid was purified by preparative HPLC (Waters Associates Prep LC/System 500, silica gel sample loaded in dichloromethane, eluted with 3:1 ethyl acetate:methanol). The appropriate fractions were combined, evaporated, dissolved in dichloromethane, filtered to remove all insoluble material, and concentrated to yield 1.70 g of a solid (26%). The products of several similar reactions were combined and repurified by preparative HPLC, as above, to yield 2.95 g of a solid, which was recrystallized from dichloromethane/ether to afford 2.39 g (26%) of (±) -1-[2-(N,N-dimethylamino)ethyl]-3-methoxy-4-phenyl-1,3,4,5-tetrahydro-2H-1,3-benzodiazepine-2-one,m.p.127°-128° C.

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