Application of reactarray robotics and design of experiments techniques in optimisation of supported reagent chemistry

Organic Process Research and Development

Volumn 6, Issue 6, 2002, Pages 823-825

  Jamieson, Craig ^a,b   Congreve, Miles S ^a,b   Emiabata Smith, David F ^a   Ley, Steven V ^b   Scicinski, Jan J ^a,b  

^a GLAXOSMITHKLINE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; ISOLEUCINE; PHENYLALANINE; PHENYLGLYCINE; PROLINE;

AUTOMATION; COMPUTER PROGRAM; CONCENTRATION (PARAMETERS); CONFERENCE PAPER; CYCLIZATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; PROTON NUCLEAR MAGNETIC RESONANCE; REACTION TIME; ROBOTICS; STOICHIOMETRY; SYNTHESIS;

EID: 0036858614     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op010108e     Document Type: Conference Paper

References (13)

1. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc. Perkin Trans. 1 2000, 3815; Parlow, J. J.; Devraj, R. V.; South, M. S.; Curr. Opin. Chem. Biol. 1999, 3, 320; Drewry, D. H.; Coe, D. M.; Poon, S. Med. Res. Rev. 1999, 19, 97.
2. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc. Perkin Trans. 1 2000, 3815; Parlow, J. J.; Devraj, R. V.; South, M. S.; Curr. Opin. Chem. Biol. 1999, 3, 320; Drewry, D. H.; Coe, D. M.; Poon, S. Med. Res. Rev. 1999, 19, 97.
3. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc. Perkin Trans. 1 2000, 3815; Parlow, J. J.; Devraj, R. V.; South, M. S.; Curr. Opin. Chem. Biol. 1999, 3, 320; Drewry, D. H.; Coe, D. M.; Poon, S. Med. Res. Rev. 1999, 19, 97.
4. For an example of the use of solid-phase chemistry in scale-up see: Raillard, S. P.; Ji, G.; Mann, A. D.; Baer, T. A. Org. Process Res. Dev. 1999, 3, 177.
5. Carlson, R. Design and Optimisation in Organic Synthesis; Elsevier: Amsterdam, 1992.
6. Emiabata-Smith, D. F.; Crookes, D. L.; Owen, M. R. Org. Process Res. Dev. 1999, 3, 281.
7. Jamieson, C.; Congreve, M. S.; Emiabata-Smith, D. F.; Ley, S. V.; Synlett 2000, 1603.
8. Weinshenker, N. M.; Shen, C. M. Tetrahedron Lett. 1972, 13, 3281.
9. Scicinski, J. J.; Congreve, M. S.; Jamieson, C.; Ley, S. V.; Newman, E. S.; Vinader, V. M.; Carr, R. A. E. J. Comb. Chem. 2001, 3, 387.
10. Pederson, O. S.; Pederson, E. B. Synthesis 2000, 479; Billhardt, U. M.; Roesner, M.; Riess, G.; Winkler, I.; Bender, R. Eur. Pat. Appl. EP509398, 1992.
11. Billhardt, U. M.; Roesner, M.; Riess, G.; Winkler, I.; Bender, R. Eur. Pat. Appl. EP509398, 1992.
12. Reaction vessels were manually charged with the appropriate resin systems and reagents added using the ReactArray as solutions in the required solvents. Each reaction was sampled (25 μL) at a given time interval and quenched with acetonitrile (600 μL). The resulting solution was allowed to stand for 2 min before an aliquot (25 μL) was automatically analysed by the instrument using an Agilent 1100 HPLC system and a Supelcosil ABZ+ Plus column (3.3 cm, 4.6 mm diameter) using the following method: eluent A water, 0.1% TFA; eluent B, acetonitrile 95%, water 5%, TFA 0.05%. Gradient: 10-95% eluent B in eluent A (1 mL/min) over 8 min. Detection: UV diode array (215, 254, 386 nm).
13. Design Expert software is copyright of the Stat-Ease Corporation, Minneapolis, MN, U.S.A.