Synthesis and evaluation of 2-NMPA derivatives as potential agents for prevention of osteoporosis in vitro and in vivo.

Abnormal osteoclast differentiation causes various bone disorders such as osteoporosis. Targeting the formation and activation of osteoclasts has been recognized as an effective approach for preventing osteoporosis. Herein, we synthesized eleven 2-NMPA derivatives which are (2-(2-chlorophenoxy)-N-(4-alkoxy-2-morpholinophenyl) acetamides, and evaluated their suppression effects on osteoclastogenesis in vitro by using TRAP-staining assay.

Reaction of Amide and Sodium Azide for the Synthesis of Acyl Azide, Urea, and Iminophosphorane.

Amides reacted with NaN to give the acyl azides in DMF at 25 °C and produce the symmetrical ureas in THF/HO at 80 °C via the sequential reaction of acyl substitution and Curtius rearrangement. All acyl azides were also obtained from the secondary amides via sequential reaction of -toluenesulfonyl chloride and NaN. In addition, keto-stabilized iminophosphoranes were prepared from a one-pot reaction of amides, NaN, and phosphines.

Metal-free transamidation of benzoylpyrrolidin-2-one and amines under aqueous conditions.

N-Acyl lactam amides, such as benzoylpyrrolidin-2-one, benzoylpiperidin-2-one, and benzoylazepan-2-one reacted with amines in the presence of DTBP and TBAI to afford the transamidated products in good yields. The reactions were conducted under aqueous conditions and good functional group tolerance was achieved. Both aliphatic and aromatic primary amines displayed good activity under metal-free conditions.

Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of β-Ketoesters.

Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method to synthesis of β-alkylketoesters using the cross-coupling between aliphatic amides and esters. Meanwhile, gram-scale secondary and primary amides reacted via in situ generated activated tertiary amides and exhibited good reactivity when coupled with esters.