Acid-facilitated debenzylation of N-Boc, N-benzyl double protected 2-aminopyridinomethyl pyrrolidine derivatives

• Published in: Tetrahedron Vol. 68; no. 5; pp. 1359 - 1366
• Main Authors: Ji, Haitao, Jing, Qing, Huang, Jinwen, Silverman, Richard B.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 04.02.2012; Elsevier
• Subjects: 2-Aminopyridinomethyl pyrrolidines; Chemistry; Chemistry, Organic; Condensed benzenic and aromatic compounds; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Mitsunobu reaction; N-Benzyl deprotection; Noncondensed benzenic compounds; Organic chemistry; Palladium-catalyzed hydrogenation; Physical Sciences; Preparations and properties; Science & Technology; Palladium-catalyzed hydrogenation; N-Benzyl deprotection; 2-Aminopyridinomethyl pyrrolidines; Mitsunobu reaction; SELECTIVE-INHIBITION; DESIGN; MONOCATIONIC INHIBITORS; ACTIVE-SITE; NITRIC-OXIDE SYNTHASE; PREVENTION; ETHERS; POTENT; MITSUNOBU REACTIONS; CEREBRAL-PALSY; Nitrogen heterocycle; Nitric oxide synthase inhibitor; Isozyme; Deprotection; Palladium complex; Selectivity; Hydrogenation; Pyrrolidine derivatives; Pyridine derivatives; Benzylic compound; Debenzylation; Aromatic compound; Secondary alcohol; Chemical synthesis; Protection; Catalytic reaction; Enzyme; Steric hindrance; Nitric-oxide synthase; Naphthol derivatives; Oxidoreductases; Acetic acid
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.12.013

2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection. [Display omitted]