A 12-step large-scale synthesis of stereochemically rich CCR2 inhibitor 1  is presented. Optically pure all-cis 1,2,4-triaminocyclohexane core was assembled via Pt-catalyzed heterogeneous hydrogenation of chiral �-enaminoester 3  using a single template stereocenter (S)-a-phenethylamine. Catalytic reduction was greatly superior to hydrides, improving faciality and yields while sharply reducing process volumes. 3-Amino-pyrrolidone was constructed through Freidinger reaction. The two remaining nitrogens at C-2 and C-4 were installed via reductive amination of ketone 2  and Curtius contraction. Quinazoline coupling completes the synthesis. 

Asymmetric synthesis of a CCR2 inhibitor featuring an optically pure all-cis (S,R,R)-1,2,4-triamino-cyclohexane core

245th National Meeting (2013)

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