A convenient one-pot preparation and applications of high loading benzhydrylamine solid phase linkers

Tetrahedron Letters

Volumn 48, Issue 11, 2007, Pages 1951-1954

  Torr, Jane E ^a   Large, Jonathan M ^a   McDonald, Edward ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

Benzhydrylamines; Cleavage; Linkers; Solid phase

Indexed keywords

AMINE; BENZHYDRYLAMINE; RESIN; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; SOLID; SYNTHESIS;

EID: 33846915948     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2007.01.077     Document Type: Article

References (20)

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9. Linkers of type 2 and 3 are both commercially available (e.g., Novabiochem, Merck Biosciences, UK) on particle sizes suitable for use in IRORI MicroKans.
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15. For a solution phase example, see:. Weiberth F.J., and Hall S.S. J. Org. Chem. 51 (1986) 5338-5341
16. nBuLi (6.4 ml, 2.5 M in hexanes) was added and the reaction was heated to 60 °C for 3 h. 4-Methoxybenzonitrile (5.30 g, 39.8 mmol, 10 equiv) was added and the reaction mixture stirred for 10 min. Methanol (2 ml) and sodium borohydride (2.80 g, 20 equiv) were added and the suspension was stirred for a further 30 min at room temperature. The resin was collected by filtration and washed with methanol (5 ml), THF (5 ml) and DCM (3 × 5 ml) and dried overnight in a dessicator to give a pale yellow solid (2.38 g). Elemental analysis: Br 0.03%, N 2.21% (loading 1.57 mmol/g). The other resins prepared using this method showed comparably low levels of remaining bromine.
17. Resin 9 is commercially available (e.g., Novabiochem, Merck Biosciences, UK).
18. A similar effect has been reported for closely related trityl resins; for example, see:. Park J.G., Langenwalter K.J., Weinbaum C.A., Casey P.J., and Pang Y.-P. J. Comb. Chem. 6 (2004) 407-413
19. Guo G., Arvanitis E.A., Pottorf R.S., and Player M.R. J. Comb. Chem. 5 (2003) 408-413
20. 3 (×4)). Elemental analysis: N 1.35% (loading 0.96 mmol/g).