Synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677

Phosphinic Peptide Matrix Metalloproteinase-9 Inhibitors by Solid-Phase Synthesis Using a Building Block Approach

“…Since large amounts of the final building block were needed for combinatorial investigations, 2 a was prepared on a multigram scale, while the synthesis was still efficient (73 % yield). Benzyloxycarbonyl (Cbz) protection of 2 a was achieved by a standard procedure [63] and the product 2 b was obtained in pure form by crystallization, although at this point the product was difficult to analyze by NMR spectroscopy. ) er beskrevet.…”

“…[63] Compound 2 a (5.00 g, 52.6 mmol) was dissolved in water with K 2 CO 3 (17.0 g, 123 mmol, 2.34 equiv), and Cbz-Cl (95 %, 10.3 mL, 68.4 mmol, 1.3 equiv) was added dropwise at 0 8C. After the solution was stirred at RT for 19 h, further CbzCl (2 Â 0.5 equiv) was added and the solution was stirred for 1 h until complete consumption of 2 a was observed.…”

A convenient synthesis of 1′-H-spiro-(indoline-3,4′-piperidine) and its derivatives

“…The Fischer indole type synthetic approach reported by Maligres et al yielded 1b, a 1 0 -Cbz-protected analog with an overall yield of 80% in five steps, but based on quantitative HPLC analysis only. 10 The two-step synthesis of 1 0 -methylated analog (1c) reported by Ong (Scheme 1) seemed to be straightforward; 11 however, in our hands, only a 20% overall yield was achieved. Subsequent 1 0 -N-demethylation with a-chloroethyl chloroformate (ACE-Cl) 12 also proved to be problematic, further limiting the use of this chemistry for our needs.…”

Novel orally active NPY Y5 receptor antagonists: Synthesis and structure–activity relationship of spiroindoline class compounds

“…Compounds 2a-aj were prepared by the urea formation between spiroindoline amine 6, which was previously synthesized and reported by our Process Research group, 25 carbamates 5 were generally made from the reaction between biaryl amines 4 and phenyl chloroformate. The aryl amines 4 were either purchased from suppliers as commercially available reagents or prepared using standard synthesis protocols.…”