[C:1]([C:3]1[N:7]2[C@@H:8]([CH3:15])[CH2:9][N:10]([CH2:13][CH3:14])[C:11](=[O:12])[C:6]2=[C:5]([O:16][CH3:17])[C:4]=1[C:18]([O:20]CC)=O)#[N:2].[NH2:23][NH2:24]>C(O)C.C(O)(=O)C>[NH2:2][C:1]1[C:3]2[N:7]3[C@@H:8]([CH3:15])[CH2:9][N:10]([CH2:13][CH3:14])[C:11](=[O:12])[C:6]3=[C:5]([O:16][CH3:17])[C:4]=2[C:18](=[O:20])[NH:24][N:23]=1A solution of ethyl (4S)-6-cyano-2-ethyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-carboxylate (1.10 g, 3.60 mmol) in absolute ethanol (25 mL) was purged with argon gas for 15 minutes. The mixture was treated with hydrazine (1.16 g, 36.02 mmol) and 20 drops glacial acetic acid, and heated in a sealed tube in an oil bath at 110° C. overnight. The product mixture was cooled to 0° C. The solid precipitated collected by filtration, washed with cold ethanol and diethyl ether to afford the title compound. The filtrate was concentrated under vacuum, and the residue was subjected to preparative high pressure reverse phase column chromatography. Collection and lyophilization of appropriate fractions provided additional product, which was concentrated from its solution in acetonitrile and anhydrous DMF prior to the following benzylation. ES MS M+1=292.
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