Solid-phase synthesis of 1-substituted tetrahydroisoquinoline derivatives employing BOC-protected tetrahydroisoquinoline carboxylic acids

Journal of Combinatorial Chemistry

Volumn 6, Issue 4, 2004, Pages 487-496

  Bunin, Barry A ^a   Dener, Jeffrey M ^a,b   Kelly, Daphne E ^a   Paras, Nick A ^a   Tario, James D ^a   Tushup, Steven P ^a  

^a Discovery Partners International   (United States)

^b CELERA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYL GROUP; AMIDE; BENZOIC ACID DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; DOPAMINE; GLYOXYLIC ACID DERIVATIVE; META TYRAMINE; RESIN; SULFIDE; TETRAHYDROISOQUINOLINE DERIVATIVE;

ARTICLE; COMBINATORIAL CHEMISTRY; CYCLIZATION; DRUG CONFORMATION; DRUG IDENTIFICATION; DRUG STRUCTURE; DRUG SYNTHESIS; ESTERIFICATION; PICTET SPENGLER REACTION; PROCESS DEVELOPMENT; PROCESS OPTIMIZATION; REACTION ANALYSIS; SOLID STATE; STRUCTURE ANALYSIS; SUBSTITUTION REACTION;

EID: 4143074949     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc0340776     Document Type: Article

References (40)

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2. For early examples, see the following, (a) Bunin, B. A.; Ellman, J. A. J. Am. Chem. Soc. 1992, 114, 10997-10998. (b) Dewitt, S. H.; Kiely, J. S.; Stankovic, C. J.; Schroeder, M. C. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6909-6913. (c) Virgilio, A. A.; Ellman, J. A. J. Am. Chem. Soc. 1994, 116, 11580-11581. (d) Chen, C.; Ahlberg Randall, L. A.; Miller, R. B.; Jones, A. D.; Kurth, M. J. J. Am. Chem. Soc. 1994, 116, 2661-2662.
3. For early examples, see the following, (a) Bunin, B. A.; Ellman, J. A. J. Am. Chem. Soc. 1992, 114, 10997-10998. (b) Dewitt, S. H.; Kiely, J. S.; Stankovic, C. J.; Schroeder, M. C. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6909-6913. (c) Virgilio, A. A.; Ellman, J. A. J. Am. Chem. Soc. 1994, 116, 11580-11581. (d) Chen, C.; Ahlberg Randall, L. A.; Miller, R. B.; Jones, A. D.; Kurth, M. J. J. Am. Chem. Soc. 1994, 116, 2661-2662.
4. For early examples, see the following, (a) Bunin, B. A.; Ellman, J. A. J. Am. Chem. Soc. 1992, 114, 10997-10998. (b) Dewitt, S. H.; Kiely, J. S.; Stankovic, C. J.; Schroeder, M. C. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6909-6913. (c) Virgilio, A. A.; Ellman, J. A. J. Am. Chem. Soc. 1994, 116, 11580-11581. (d) Chen, C.; Ahlberg Randall, L. A.; Miller, R. B.; Jones, A. D.; Kurth, M. J. J. Am. Chem. Soc. 1994, 116, 2661-2662.
5. For reviews on the combinatorial synthesis of small molecules, see the following, (a) Seneci, P. Solid-Phase Synthesis and Combinatorial Technologies; Wiley: New York, 2000. (b) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600. (d) Bunin, B. A. The Combinatorial Index; Academic Press: San Diego, 1997; (e) J. S. Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17-42. (f) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
6. For reviews on the combinatorial synthesis of small molecules, see the following, (a) Seneci, P. Solid-Phase Synthesis and Combinatorial Technologies; Wiley: New York, 2000. (b) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600. (d) Bunin, B. A. The Combinatorial Index; Academic Press: San Diego, 1997; (e) J. S. Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17-42. (f) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
7. For reviews on the combinatorial synthesis of small molecules, see the following, (a) Seneci, P. Solid-Phase Synthesis and Combinatorial Technologies; Wiley: New York, 2000. (b) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600. (d) Bunin, B. A. The Combinatorial Index; Academic Press: San Diego, 1997; (e) J. S. Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17-42. (f) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
8. For reviews on the combinatorial synthesis of small molecules, see the following, (a) Seneci, P. Solid-Phase Synthesis and Combinatorial Technologies; Wiley: New York, 2000. (b) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600. (d) Bunin, B. A. The Combinatorial Index; Academic Press: San Diego, 1997; (e) J. S. Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17-42. (f) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
9. For reviews on the combinatorial synthesis of small molecules, see the following, (a) Seneci, P. Solid-Phase Synthesis and Combinatorial Technologies; Wiley: New York, 2000. (b) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600. (d) Bunin, B. A. The Combinatorial Index; Academic Press: San Diego, 1997; (e) J. S. Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17-42. (f) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
10. For reviews on the combinatorial synthesis of small molecules, see the following, (a) Seneci, P. Solid-Phase Synthesis and Combinatorial Technologies; Wiley: New York, 2000. (b) Obrecht, D.; Villalgordo, J. M. Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries; Pergamon: Oxford, 1998. (c) Ellman, J. A.; Thompson, L. A. Chem. Rev. 1996, 96, 555-600. (d) Bunin, B. A. The Combinatorial Index; Academic Press: San Diego, 1997; (e) J. S. Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17-42. (f) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
11. Compound 1a: Thorwart, W.; Schwab, W.; Schudok, M.; Haase, B.; Bartnik, E.; Weithmann, K.-U. WO 97/18194, published 22 May 1997. Compound 1b: Semple, G.; Ryder, H.; Kendrick, D. A.; Batt, A. R.; Mathews, E.; Rooker, D. P.; Szelke, M.; Nishida, A.; Miyata, K. Bioorg. Med. Chem. Lett. 1996, 6, 2971-2976. See also the following: (a) VanAtten, M. K.; Ensinger, C. L.; Chiu, A. T.; McCall. D. E.; Nguyen, T. T.; Wexler, R. R.; Timmermans, P. B. M. W. M. J. Med. Chem. 1993, 36, 3985-3992. (b) Hayashi, K.; Nunami, K.-i.; Sakai, K.; Ozaki, Y.; Kato, J.; Kinashi, K.; Yoneda, N. Chem. Pharm. Bull. 1985, 33, 2011-2022.
12. Compound 1a: Thorwart, W.; Schwab, W.; Schudok, M.; Haase, B.; Bartnik, E.; Weithmann, K.-U. WO 97/18194, published 22 May 1997. Compound 1b: Semple, G.; Ryder, H.; Kendrick, D. A.; Batt, A. R.; Mathews, E.; Rooker, D. P.; Szelke, M.; Nishida, A.; Miyata, K. Bioorg. Med. Chem. Lett. 1996, 6, 2971-2976. See also the following: (a) VanAtten, M. K.; Ensinger, C. L.; Chiu, A. T.; McCall. D. E.; Nguyen, T. T.; Wexler, R. R.; Timmermans, P. B. M. W. M. J. Med. Chem. 1993, 36, 3985-3992. (b) Hayashi, K.; Nunami, K.-i.; Sakai, K.; Ozaki, Y.; Kato, J.; Kinashi, K.; Yoneda, N. Chem. Pharm. Bull. 1985, 33, 2011-2022.
13. Compound 1a: Thorwart, W.; Schwab, W.; Schudok, M.; Haase, B.; Bartnik, E.; Weithmann, K.-U. WO 97/18194, published 22 May 1997. Compound 1b: Semple, G.; Ryder, H.; Kendrick, D. A.; Batt, A. R.; Mathews, E.; Rooker, D. P.; Szelke, M.; Nishida, A.; Miyata, K. Bioorg. Med. Chem. Lett. 1996, 6, 2971-2976. See also the following: (a) VanAtten, M. K.; Ensinger, C. L.; Chiu, A. T.; McCall. D. E.; Nguyen, T. T.; Wexler, R. R.; Timmermans, P. B. M. W. M. J. Med. Chem. 1993, 36, 3985-3992. (b) Hayashi, K.; Nunami, K.-i.; Sakai, K.; Ozaki, Y.; Kato, J.; Kinashi, K.; Yoneda, N. Chem. Pharm. Bull. 1985, 33, 2011-2022.
14. Compound 1a: Thorwart, W.; Schwab, W.; Schudok, M.; Haase, B.; Bartnik, E.; Weithmann, K.-U. WO 97/18194, published 22 May 1997. Compound 1b: Semple, G.; Ryder, H.; Kendrick, D. A.; Batt, A. R.; Mathews, E.; Rooker, D. P.; Szelke, M.; Nishida, A.; Miyata, K. Bioorg. Med. Chem. Lett. 1996, 6, 2971-2976. See also the following: (a) VanAtten, M. K.; Ensinger, C. L.; Chiu, A. T.; McCall. D. E.; Nguyen, T. T.; Wexler, R. R.; Timmermans, P. B. M. W. M. J. Med. Chem. 1993, 36, 3985-3992. (b) Hayashi, K.; Nunami, K.-i.; Sakai, K.; Ozaki, Y.; Kato, J.; Kinashi, K.; Yoneda, N. Chem. Pharm. Bull. 1985, 33, 2011-2022.
15. Compound 2a: Schiller, P. WO 96/06855, published 7 March 1996. Compound 2b: Clerc, F. PCT WO 96/24612, published 15 August 1996. See also the following: Bateson, J. H.; Gilpin, M. L. PCT WO 98/39311, published 11 September 1998.
16. Compound 2a: Schiller, P. WO 96/06855, published 7 March 1996. Compound 2b: Clerc, F. PCT WO 96/24612, published 15 August 1996. See also the following: Bateson, J. H.; Gilpin, M. L. PCT WO 98/39311, published 11 September 1998.
17. Compound 2a: Schiller, P. WO 96/06855, published 7 March 1996. Compound 2b: Clerc, F. PCT WO 96/24612, published 15 August 1996. See also the following: Bateson, J. H.; Gilpin, M. L. PCT WO 98/39311, published 11 September 1998.
18. For reviews and key references on the Pictet-Spengler reaction, see the following: (a) Whaley, W. M.; Govindchari, T. R. Org. React. 1951, 6, 151-190. (b) Bates, H. A.; Bagheri, K.; Vertino, P. M. J. Org. Chem. 1986, 51, 3061-3063. For an example of the synthesis of related tetrahydroisoquinolines via Pictet-Spengler cyclization with solid supported imines, see the following: Sun, Q.; Kyle, D. J. Comb. Chem. High Throughput Screening 2002, 5, 75-81. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1996, 37, 4865-4868.
19. For reviews and key references on the Pictet-Spengler reaction, see the following: (a) Whaley, W. M.; Govindchari, T. R. Org. React. 1951, 6, 151-190. (b) Bates, H. A.; Bagheri, K.; Vertino, P. M. J. Org. Chem. 1986, 51, 3061-3063. For an example of the synthesis of related tetrahydroisoquinolines via Pictet-Spengler cyclization with solid supported imines, see the following: Sun, Q.; Kyle, D. J. Comb. Chem. High Throughput Screening 2002, 5, 75-81. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1996, 37, 4865-4868.
20. For reviews and key references on the Pictet-Spengler reaction, see the following: (a) Whaley, W. M.; Govindchari, T. R. Org. React. 1951, 6, 151-190. (b) Bates, H. A.; Bagheri, K.; Vertino, P. M. J. Org. Chem. 1986, 51, 3061-3063. For an example of the synthesis of related tetrahydroisoquinolines via Pictet-Spengler cyclization with solid supported imines, see the following: Sun, Q.; Kyle, D. J. Comb. Chem. High Throughput Screening 2002, 5, 75-81. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1996, 37, 4865-4868.
21. For reviews and key references on the Pictet-Spengler reaction, see the following: (a) Whaley, W. M.; Govindchari, T. R. Org. React. 1951, 6, 151-190. (b) Bates, H. A.; Bagheri, K.; Vertino, P. M. J. Org. Chem. 1986, 51, 3061-3063. For an example of the synthesis of related tetrahydroisoquinolines via Pictet-Spengler cyclization with solid supported imines, see the following: Sun, Q.; Kyle, D. J. Comb. Chem. High Throughput Screening 2002, 5, 75-81. Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1996, 37, 4865-4868.
22. Namavari, M.; Satyamurthy, N.; Barrio, J. R. J. Fluorine Chem. 1995, 74, 113-121.
23. (b) Hashima, H.; Hayashi, M.; Kamano, Y.; Sato, N. Bioorg. Med. Chem. 2000, 8, 1757-1766.
24. Ornstein, P. L.; Schoepp, D. D.; Arnold, M. B.; Augenstein, N. K.; Lodge, D.; Millar, J. D.; Chambers, J.; Campbell, J.; Paschal, J. W.; Zimmerman, D. M.; Leander, J. D. J. Med. Chem. 1992, 55, 3547-3560.
25. Marshall, D. L.; Liener, I. E. J. Org. Chem. 1970, 35, 867-878.
26. We have established this resin to be extremely valuable for the synthesis of combinatorial libraries, as illustrated by the following examples: (a) Breitenbucher, J. G.; Hui, H. C. Tetrahedron Lett. 1998, 39, 8207-8210. (b) Breitenbucher, J. G.; Johnson, C. R.; Haight, M.; Phelan, J. C. Tetrahedron Lett. 1998, 39, 1295-1298. (c) Fantauzzi, P. P.; Yager, K. M. Tetrahedron Lett. 1998, 39, 1291-1294. (d) Boldi, A. M.; Dener, J. M.; Hopkins, T. P. J. Comb. Chem. 2001, 3, 367-373.
27. We have established this resin to be extremely valuable for the synthesis of combinatorial libraries, as illustrated by the following examples: (a) Breitenbucher, J. G.; Hui, H. C. Tetrahedron Lett. 1998, 39, 8207-8210. (b) Breitenbucher, J. G.; Johnson, C. R.; Haight, M.; Phelan, J. C. Tetrahedron Lett. 1998, 39, 1295-1298. (c) Fantauzzi, P. P.; Yager, K. M. Tetrahedron Lett. 1998, 39, 1291-1294. (d) Boldi, A. M.; Dener, J. M.; Hopkins, T. P. J. Comb. Chem. 2001, 3, 367-373.
28. We have established this resin to be extremely valuable for the synthesis of combinatorial libraries, as illustrated by the following examples: (a) Breitenbucher, J. G.; Hui, H. C. Tetrahedron Lett. 1998, 39, 8207-8210. (b) Breitenbucher, J. G.; Johnson, C. R.; Haight, M.; Phelan, J. C. Tetrahedron Lett. 1998, 39, 1295-1298. (c) Fantauzzi, P. P.; Yager, K. M. Tetrahedron Lett. 1998, 39, 1291-1294. (d) Boldi, A. M.; Dener, J. M.; Hopkins, T. P. J. Comb. Chem. 2001, 3, 367-373.
29. We have established this resin to be extremely valuable for the synthesis of combinatorial libraries, as illustrated by the following examples: (a) Breitenbucher, J. G.; Hui, H. C. Tetrahedron Lett. 1998, 39, 8207-8210. (b) Breitenbucher, J. G.; Johnson, C. R.; Haight, M.; Phelan, J. C. Tetrahedron Lett. 1998, 39, 1295-1298. (c) Fantauzzi, P. P.; Yager, K. M. Tetrahedron Lett. 1998, 39, 1291-1294. (d) Boldi, A. M.; Dener, J. M.; Hopkins, T. P. J. Comb. Chem. 2001, 3, 367-373.
30. Johnson, C. R.; Zhang, B.; Fantauzzi, P.; Hocker, M.; Yager, K. M. Tetrahedron 1998, 54, 4097-4106. See also Breitenbucher, J. G.; Johnson, C. R.; Haight, M.; Phelan, J. C. Tetrahedron Lett. 1998, 39, 1295-1298.
31. Johnson, C. R.; Zhang, B.; Fantauzzi, P.; Hocker, M.; Yager, K. M. Tetrahedron 1998, 54, 4097-4106. See also Breitenbucher, J. G.; Johnson, C. R.; Haight, M.; Phelan, J. C. Tetrahedron Lett. 1998, 39, 1295-1298.
32. The synthetic utility of cyclicative cleavage reactions in solid-phase organic synthesis has been recently reviewed. Park, K.-H.; Kurth, M. J. Drugs Fut. 2000, 25, 1265-1294. Van Maarseveen, J. H. Comb. Chem. High Throughput Screening 1998, 1, 185-214.
33. The synthetic utility of cyclicative cleavage reactions in solid-phase organic synthesis has been recently reviewed. Park, K.-H.; Kurth, M. J. Drugs Fut. 2000, 25, 1265-1294. Van Maarseveen, J. H. Comb. Chem. High Throughput Screening 1998, 1, 185-214.
34. For representative hydantoin syntheses via this strategy, note the following examples: (a) Peng, G.; Sohn, A.; Gallop, M. J. Org. Chem. 1999, 64, 8342-8349. (b) Park, K.-H.; Olmstead, M. M.; Kurth, M. J. J. Org. Chem. 1998, 63, 6579-6585. (c) Mathews, J.; Rivero, R. A. J. Org. Chem. 1997, 62, 6090-6092. (d) Kim, S. W.; Ahn, S. Y.; Koh, J. S.; Lee, J. H.; Ro, S.; Cho, H. Y. Tetrahedron Lett. 1997, 38, 4603-4606.
35. For representative hydantoin syntheses via this strategy, note the following examples: (a) Peng, G.; Sohn, A.; Gallop, M. J. Org. Chem. 1999, 64, 8342-8349. (b) Park, K.-H.; Olmstead, M. M.; Kurth, M. J. J. Org. Chem. 1998, 63, 6579-6585. (c) Mathews, J.; Rivero, R. A. J. Org. Chem. 1997, 62, 6090-6092. (d) Kim, S. W.; Ahn, S. Y.; Koh, J. S.; Lee, J. H.; Ro, S.; Cho, H. Y. Tetrahedron Lett. 1997, 38, 4603-4606.
36. For representative hydantoin syntheses via this strategy, note the following examples: (a) Peng, G.; Sohn, A.; Gallop, M. J. Org. Chem. 1999, 64, 8342-8349. (b) Park, K.-H.; Olmstead, M. M.; Kurth, M. J. J. Org. Chem. 1998, 63, 6579-6585. (c) Mathews, J.; Rivero, R. A. J. Org. Chem. 1997, 62, 6090-6092. (d) Kim, S. W.; Ahn, S. Y.; Koh, J. S.; Lee, J. H.; Ro, S.; Cho, H. Y. Tetrahedron Lett. 1997, 38, 4603-4606.
37. For representative hydantoin syntheses via this strategy, note the following examples: (a) Peng, G.; Sohn, A.; Gallop, M. J. Org. Chem. 1999, 64, 8342-8349. (b) Park, K.-H.; Olmstead, M. M.; Kurth, M. J. J. Org. Chem. 1998, 63, 6579-6585. (c) Mathews, J.; Rivero, R. A. J. Org. Chem. 1997, 62, 6090-6092. (d) Kim, S. W.; Ahn, S. Y.; Koh, J. S.; Lee, J. H.; Ro, S.; Cho, H. Y. Tetrahedron Lett. 1997, 38, 4603-4606.
38. We have also observed hydantoin formation upon attempts to form amides from support-bound ureido derivatives of other α-amino esters of resin 15. Ester derivatives of resin 15 have been employed to generate the hydantoin ring system exclusively. See: Boldi, A. M.; Johnson, C. R. In Optimization of Solid-Phase Combinatorial Synthesis; Yan, B., Czarnik, A. W., Eds; Marcel Dekker: New York, 2001; 1-27.
39. Recently, a modified version of the method for determination of loading of Marshall resin described herein has also been reported in the context of recycling of the resin. Irving, M. M.; Kshirsagar, T.; Figliozzi, G. M.; Yan B. J. Comb. Chem. 2001, 3, 407-409.
40. Fang, L.; Pan, J.; Yan, B. Biotechnol. Bioeng. 2000, 71, 162-171.