Generation of Secondary Alkyl Amines on Solid Support by Borane Reduction: Application to the Parallel Synthesis of PPAR Ligands

Solid-Phase Synthesis of Acyclic and Cyclic Amino Acid Derived Urea Peptidomimetics Using Phoxime Resin

“…Synthesis of 3-Aminohydantoins (7) vs 1,2,4-Triazine-3,6-diones (8). The coupling of resin 3 with mono-or disubstituted hydrazine under standard carbodiimide conditions (HOBt/DIC in DMF) afforded carbamate hydrazide resin 6 (Scheme 2).…”

“…General Thermolysis Procedure for the Preparation of 1,2,4-Triaza-3,6-dione (8). To a solution of DIPEA (5.0 mmol) in DMF (10 mL) was added resin 11 (0.50 mmol), and the mixture was shaken at 80°C for 24 h. The resulting resin was collected on a glass filter and washed with DMF × 4, MeOH × 4, and CH 2 Cl 2 × 3.…”

Design and Synthesis of Protein Superfamily-Targeted Chemical Libraries for Lead Identification and Optimization

“…Solid phase parallel synthesis of a 16-member PPAR ligand array was reported by Brown [192]. The key reaction in this route was a novel borane reduction of resin-bound amides that generated secondary amines which were not accessible via reductive alkylation of primary amines.…”

“…Starting from a simple template benzamide, several lead compounds of the type (192) were identified using a virtual screening-driven SAR exercise. (Table VIII) Matrix Metalloproteases (MMPs) are a family of mammalian proteases dependent upon zinc for catalysis and calcium for activity and stability.…”

Recent developments in solid-phase organic synthesis

“…A solution is to adopt a two-step procedure involving amide formation followed by a selective reduction with borane to provide the desired secondary amines. 122 An extension of this strategy to provide a linker for N-methylamines can be seen in Scheme 90. 123 Resin-bound nitrogen containing compounds with acidic protons can be deprotonated to facilitate alkylation (see Schemes 43,46 and 105).…”