Alternative solvents for elevated-temperature solid-phase parallel synthesis. Application to thionation of amides

Organic Letters

Volumn 5, Issue 5, 2003, Pages 721-724

  Coats, Steven J ^a   Link, Jeffrey S ^a   Hlasta, Dennis J ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PYRROLIDONE DERIVATIVE; AMIDE; BENZENE DERIVATIVE; BENZYL BENZOATE; CORN OIL; DICHLOROMETHANE; DIETHYLENE GLYCOL; ETHER DERIVATIVE; ETHYLAMINE; HEXADECANE; MINERAL OIL; NAPHTHALENE DERIVATIVE; NITRILE; OCTYLAMINE; PYRIDINE DERIVATIVE; SILICONE OIL; SOLVENT; TOLUENE;

ARTICLE; CHEMICAL REACTION KINETICS; HIGH TEMPERATURE; SOLVENT EFFECT; SYNTHESIS; TEMPERATURE DEPENDENCE; VAPOR PRESSURE;

EID: 0141853294     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol027493s     Document Type: Article

References (36)

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8. Library synthesis: (a) Dolle, R. E. J. Comb. Chem. 2002, 4, 369-418. (b) Dolle, R. E. J. Comb. Chem. 2001, 3, 477-517. (c) Booth, S.; Hermkens, P. H. H. ; Ottenheijm, H. C. J.; Rees, D. C. Tetrahedron 1998, 54, 15385-15443. (d) Franzen, R. G. J. Comb. Chem. 2000, 2, 195-214. (e) Dolle, R. E. Mol. Diversity 1998, 3, 199-233.
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10. Library synthesis: (a) Dolle, R. E. J. Comb. Chem. 2002, 4, 369-418. (b) Dolle, R. E. J. Comb. Chem. 2001, 3, 477-517. (c) Booth, S.; Hermkens, P. H. H. ; Ottenheijm, H. C. J.; Rees, D. C. Tetrahedron 1998, 54, 15385-15443. (d) Franzen, R. G. J. Comb. Chem. 2000, 2, 195-214. (e) Dolle, R. E. Mol. Diversity 1998, 3, 199-233.
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14. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
15. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
16. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
17. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
18. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
19. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
20. For some discussions of solvent effects, resin kinetics, and resin reaction rates see: (a) Gerritz, S. W.; Trump, R. P.; Zuercher, W. J. J. Am. Chem. Soc. 2000, 122, 6357-6363. (b) Li, W.; Xiao, X.; Czarnik, A. W. J. Comb. Chem. 1999, 1, 127-129. (c) Li, W.; Czarnik, A. W.; Lillig, J.; Xiao, X.-Y. J. Comb. Chem. 2000, 2, 224-227. (d) Merrifield, B. Br. Polym. J. 1984, 16, 173-178. (e) Li, W.; Yan, B. J. Org. Chem. 1998, 63, 4092-4097. (f) Yan, B.; Kumaravel, G.; Anjaria, H.; Wu, A.; Petter, R.; Jewell, C. F., Jr.; Wareing, J. R. J. Org. Chem. 1995, 60, 5736-5738. (g) Yan, B.; Fell, J. B.; Kumaravel, G. J. Org. Chem. 1996, 61, 7467-7472.
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24. Wang resin, 200-400 mesh, 0.97 mmol/g, Novabiochem catalog no. 01-64-0001; REM resin, 100-200 mesh, 0.84 mmol/g, Novabiochem catalog no. 01-64-0302; Merrifield resin, 100-200 mesh, 1.34 mmol/g, Novabiochem catalog no. 01-64-0104; Rink resin, 100-200 mesh, 0.7 mmol/g, Advanced ChemTech catalog no. SA5030; Tentagel S AM, 0.24 mmol/g, Rapp Polymere catalog no. S30 022
25. (a) Formation of thiazoles from α-bromo ketones and resin-bound thioamides in silicon oil and mineral oil. (b) Stille reaction with a resin-bound stannane and 4-bromoanisole in silicon oil; comparable yield to NMP. (c) 1,3-Dipolar cycloaddition of a resin-bound alkyne with benzyl azide in silicon oil, mineral oil, Edwards pump oil (ultra grade), and corn oil; yields were comparable to those in toluene.
26. (a) Pederson, B. S.; Scheibye, S.; Nilsson, N. H.; Lawesson, S.-O. Bull. Soc. Chim. Belg. 1978, 87, 223-228
27. (b) Scheibye, S.; Pederson, B. S.; Lawesson, S.-O. Bull. Soc. Chim. Belg. 1978, 87, 229-238
28. (c) Shabana, R.; Scheibye, S.; Clausen, K.; Olesen, S.-O.; Lawesson, S.-O. Nouv. J. Chim. 1980, 4, 47-51.
29. (d) Cava, M. P.; Levinson, M. I. Tetrahedron 1985, 41, 5061-5087 and references therein.
30. Pons, J. F.; Mishir, Q.; Nouvet, A.; Brookfield, F. Tetrahedron Lett. 2000, 41, 4965-4968.
31. Solvents were dispensed without special equipment or requirements. Diphenylmethane was warmed gently before dispensing. In the case of solvents that have higher viscosity, we found it useful to add dichloromethane or another appropriate solvent to the cooled reaction slurry prior to filtration.
32. Resin loading was determined as follows: 0.5 g of amide resin 2 was exposed to 6 mL of 10% TFA/DCM for 1 h. The solution was removed by filtration, and the resin was washed three times with 6 mL of 1% TFA in DCM. The TFA cleavage and wash cycle was repeated, and the combined filtrates were concentrated and purified by MPLC on silica gel to give 41 mg (0.264 mmol) of 4-chlorobenzamide as an off-white solid.
33. Rink amide 2 (0.25 g, 0.132 mmol), Lawesson's reagent 1 (107 mg, 0.132 mmol), and benzoyl benzoate (1.5 mL) were placed in a vial with a magnetic stir bar. The vial was placed in an oil bath preheated to 115°C and allowed to react for 5 min with magnetic stirring. The resulting slurry was cooled, filtered, and washed three times with DCM/MeOH and three times with DCM. The resin 3 was cleaved with 30% TFA/DCM for 1.5 h, filtered, washed 3 x 1% TFA/DCM. The combined filtrate and washings were concentrated under vacuum and then purified on silica gel (10-30% EtOAc/Hex) to give 4-chlorothiobenzamide 4 (22.4 mg, 99%) as a yellow solid.
34. Pederson, B. S.; Scheibye, S.; Clausen, K.; Lawesson, S.-O. Bull. Soc. Chim. Belg. 1978, 87, 293-297.
35. Bohdan Miniblock in the 48 position configuration with 4 mL sintered glass vessels was utilized. Mixing was performed on a Bohdan/Labline orbital shaker set at 7.5.
36. + 287.0854, found 287.0863.