Pilot-plant preparation of an αvβ3 integrin antagonist. Part 2. Synthesis of N-[2-(5-hydroxy-4,6- tetrahydropyrimidine)]-3-amino-5-hydroxybenzoic acid

Organic Process Research and Development

Volumn 8, Issue 4, 2004, Pages 571-575

  Clark, Jerry D ^a   Collins, Joe T ^a   Kleine, H Peter ^a   Weisenburger, Gerald A ^a   Anderson, D Keith ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,3 DIAMINOPROPAN 2 OL; 2 PROPANOL; 3 AMINO 5 HYDROXYBENZOIC ACID; HYDROXYBENZOIC ACID DERIVATIVE; ISOTHIOCYANIC ACID DERIVATIVE; METHYLISOTHIOCYANATE; N [2 (5 HYDROXY 4,6 TETRAHYDROPYRIMIDINE)] 3 AMINO 5 HYDROXYBENZOIC ACID; UNCLASSIFIED DRUG; VITRONECTIN RECEPTOR;

ARTICLE; PROCESS DEVELOPMENT; SYNTHESIS;

EID: 4243164423     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op049968w     Document Type: Article

References (13)

1. (a) Eliceiri, B. P.; Cheresh, D. A. Cancer 2000, 6S3, 245-249.
2. (b) Roberto, R.; Angelo, V.; Domenico, R.; Francesco, D. R.; Francesca, M.; Franco, D. Haematologica 2002, 87, 836-845.
3. (c) Ruminski, P. G.; Rogers, T. E.; Rico, J. E.; Nickols, G. A.; Westlin, W. F.; Engleman, V. W.; Settle, S. L.; Keene, J. L.; Freeman, S. K.; Carron, C. P.; Meyer, D. M. Abstracts of Papers, 218th National Meeting of the American Chemical Society, New Orleans, LA; American Chemical Society: Washington, DC, 1999.
4. (d) Ruminski, P. G.; Rogers, T. E.; Rico, J. E.; Nickols, G. A.; Engleman, V. W.; Settle, S. L.; Keene, J. L.; Freeman, S. K.; Carron, C. P.; Meyer, D. M. Abstracts of Papers, 217th National Meeting of the American Chemical Society, Anaheim, CA; American Chemical Society: Washington, DC, 1999.
5. (e) Flynn, D. L.; Abood, N.; Bovy, P.; Garland, R.; Hockerman, S.; Lindmark, R. J.; Schretzman, L.; Rico, J.; Rogers, T. Abstracts of Papers, 210th National Meeting of the American Chemical Society, Chicago, IL; American Chemical Society: Washington, DC, 1995.
6. (a) Collins, J. T.; Devadas, B.; Lu, H.-F.; Malecha, J. W.; Miyashiro, J. M.; Nagarajan, S.; Rico, J. G.; Rogers, T. E. U.S. Patent 6,100,423, 2000.
7. (b) Bloom, B. M. U.S. Patent 2,899,426, 1959.
8. Clark, J. D.; Weisenburger, G. A.; Anderson, D. A.; Colson, P.-.J.; Edney, A. D.; Gallagher, D. J.; Kleine, H. P.; Knable, C. M.; Lantz, M. K.; Moore, C. M. V.; Murphy, J. B.; Rogers, T. E.; Ruminski, P. G.; Shah, A. S.; Storer, N.; Wise, B. E. Org. Process Res. Dev. 2004, 8, 51-61.
9. For the literature preparation of 9 see: (a) Becker, A. M.; Rickards, R. W.; Brown, R. F. C. Tetrahedron 1983, 39, 4189-4192. (b) Drake, N. L. Org. React. 1942, 5, 105-128.
10. For the literature preparation of 9 see: (a) Becker, A. M.; Rickards, R. W.; Brown, R. F. C. Tetrahedron 1983, 39, 4189-4192. (b) Drake, N. L. Org. React. 1942, 5, 105-128.
11. No impurity derived from the expulsion of methyl mercaptan was observed.
12. Intermediate 2 was a proposed registered starting material.
13. The effect of the water associated with 2 on the downstream chemistry to prepare 1 will be a subject of discussion in part three of this series.