Selective β-hydroxyethylation at the N-1 position of a pyrazolone: Synthesis of benzyl 1-(β-hydroxyethyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazole-4-carboxylate

Synlett

Volumn , Issue 7, 2008, Pages 1005-1008

  Siegmund, Aaron ^a   Retz, Daniel ^a   Xi, Ning ^a   Dominguez, Celia ^b   Bürli, Roland ^a   Liu, Longbin ^a  

^a AMGEN INC   (United States)

^b CHDI MANAGEMENT CHDI FOUNDATION   (United States)

Author keywords

Epoxide; Hydroxyethyl; Magnesium perchlorate; Pyrazole; Pyrazolones; Selective; Trimethylaluminum

Indexed keywords

ALUMINUM DERIVATIVE; BENZYL 1 (BETA HYDROXYETHYL) 5 METHYL 3 OXO 2 PHENYL 2,3 DIHYDRO 1H PYRAZOLE 4 CARBOXYLATE; CARBOXYLIC ACID DERIVATIVE; EPOXIDE; MAGNESIUM DERIVATIVE; OXIDE; PYRAZOLONE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; RING OPENING; STEREOCHEMISTRY; SYNTHESIS;

EID: 42949126801     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2008-1042923     Document Type: Article

References (38)

1. For a detailed discussion on the tautomerism of pyrazolones, see: (a) Holzer, W.; Kautsch, C.; Laggner, C.; Claramunt, R. M.; Pérez-Torralba, M.; Alkorta, I.; Elguero, J. Tetrahedron 2004, 60, 6791; and references cited therein.
2. (b) Katritzky, A. R.; Maine, F. W. Tetrahedron 1964, 20, 299.
3. For the synthesis of 4-acyl/carboxyl pyrazolones, see: (a) Jensen, B. S. Acta Chem. Scand. 1959, 13, 1668.
4. (b) Lopez, R.; León, G.; Oliva, A. J. Heterocycl. Chem. 1995, 32, 1377.
5. For examples of reactions at C-4, see: (a) Bromination/nitration: Das, S.; Mittra, A. S. J. Indian Chem. Soc. 1978, 55, 520.
6. (b) Azirine formation: Holzer, W.; Claramunt, R. M.; Pérez- Torralba, M.; Guggi, D.; Brehmer, T. H. J. Org. Chem. 2003, 68, 7943.
7. (a) Holzer, W.; Plagens, B.; Lorenz, K. Heterocycles 1997, 45, 309.
8. (b) Subasinghe, N. L.; Ali, F.; Illig, C. R.; Rudolph, M. J.; Lein, S.; Khalil, E.; Soll, R. M.; Bone, R. F.; Spurlino, J. C.; Des Jarlais, R. L.; Crysler, C. S.; Cummings, M. D.; Morris, P. E. Jr.; Kilpatrick, J. M.; Babu, Y. S. Bioorg. Med. Chem. Lett. 2004, 14, 3043.
9. 1H NMR chemical shifts: (a) Ogawa, K.; Terada, T.; Honna, T. Chem. Pharm. Bull. 1984, 32, 930.
10. (b) Bregant, N.; Perina, I.; Malnar, M. Croat. Chim. Acta 1977, 49, 813.
11. (a) Holzer, W.; Plagens, B. Sci. Pharm. 1996, 64, 455; and references cited therein.
12. (b) Holzer, W.; Schmid, E. J. Heterocycl. Chem. 1995, 32, 1341.
13. (a) Terebenina, A.; Dimitrova, K.; Iordanov, B.; Chervenakov, P.; Borisov, G. Izv. Khim. 1985, 18, 31;
14. Chem. Abstr. 1986, 104, 148787.
15. (b) JP 59181259, 1984; Chem. Abstr. 1985, 102, 113480.
16. (a) Khan, M. A.; Ellis, G. P.; Pagotto, M. C. J. Heterocycl. Chem. 2001, 38, 193.
17. (b) Rachedi, Y.; Hamdi, M.; Sakellariou, R.; Speziale, V. Synth. Commun. 1991, 21, 1189.
18. (c) Wise, L. D.; Butler, D. E.; DeWald, H. A.; Lustgarten, D. M.; Pattison, I. C.; Schweiss, D. N.; Coughenour, L. L.; Downs, D. A.; Heffner, T. G.; Pugsley, T. A. J. Med. Chem. 1987, 30, 1807.
19. Holzer, W.; Hahn, K. J. Heterocycl. Chem. 2003, 40, 303.
20. (a) Juršić, B.; Bregant, N. Synth. Commun. 1989, 19, 2087.
21. (b) Holzer, W.; Hahn, K.; Brehmer, T.; Claramunt, R. M.; Pérez-Torralba, M. Eur. J. Org. Chem. 2003, 1209.
22. (a) Sanghvi, Y. S.; Upadhya, K. G.; Dalley, N. K.; Ronibs, R. K.; Revankar, G. R. Nucleosides Nucleotides 1987, 6, 737.
23. (b) Anderson, J.; Cottam, H. B.; Larson, S. B. J. Heterocycl. Chem. 1989, 27, 439.
24. (c) Esanu, A. BE 902231, 1985; Chem. Abstr. 1986, 104, 110121.
25. (a) Alberty, J. E.; Hukki, J.; Laitinen, P.; Myry, J. Arzneim. Forsch. 1967, 17, 214;
26. Chem. Abstr., 1967, 67, 43734.
27. (b) Sammour, A.; Raouf, A. A.-E.; Elkasaby, M.; Hassan, M. A. Egypt. J. Chem. 1972, 15, 429.
28. Chiba, P.; Holzer, W.; Landau, M.; Bechmann, G.; Lorenz, K.; Plagens, B.; Hitzler, M.; Richter, E.; Ecker, G. J. Med. Chem. 1998, 41, 4001.
29. The only other example relevant to epoxide opening is found in the reaction of pyrazolone with the intermediate derived from pyrimidone and epichlorohydrin under basic conditions, possibly proceeded via an epoxide intermediate formed in situ: Krivonogov, V. P.; Kozlova, G. G.; Sivkova, G. A.; Spirikhin, L. V.; Abdrakhmanov, I. B.; Murinov, Yu. I.; Tolstikov, G. A. Russ. J. Org. Chem. 2003, 39, 257.
30. Duprez, V.; Heumann, A. Tetrahedron Lett. 2004, 45, 5697.
31. The structure of 2 was confirmed based on an alternative synthesis in ca. 10% overall yield (Scheme 2).
32. 2 (40 g) chromatography eluting with 25-75% of EtOAc in hexane.
33. 1), δ in ppm] data are provided for compounds listed in Table 1: Compound 4: 0.95 (d, J = 6.26 Hz, 3 H), 2.65 (s, 3 H), 3.38 (dd, J = 14.87, 1.76 Hz, 1 H), 3.43 (s, 1 H), 3.65 (dd, J = 14.97, 9.88 Hz, 1 H), 3.94-4.05 (m, 1 H), 5.23 (s, 2 H), 7.20-7.39 (m, 5 H) 7.39-7.49 (m, 5 H). Compounds 5 and 6: 0.74 (t, J = 7.43 Hz, 3 H), 1.18-1.37 (m, 2 H), 2.67 (s, 3 H), 3.55 (d, J = 13.30 Hz, 1 H), 3.61-3.77 (m, 2 H), 5.27 (d, J = 3.52 Hz, 2 H), 7.27-7.39 (m, 5 H), 7.41-7.51 (m, 5 H). Compound 7: 2.68 (s, 3 H), 3.21-3.34 (m, 2 H), 3.65-3.78 (m, 1 H), 3.80-3.90 (m, 1 H), 4.02-4.12 (m, 1 H), 5.16-5.31 (m, 2 H), 5.73 (br s, 1 H), 7.28-7.35 (m, 5 H), 7.36-7.51 (m, 5 H). Compound 8: 0.68 (d, J = 6.85 Hz, 3 H), 0.74 (d, J = 6.85 Hz, 3 H), 1.49 (dd, J = 12.81, 6.75 Hz, 1 H), 2.67 (s, 3 H), 3.25 (br s, 1 H), 3.46-3.53 (m, 1 H), 3.58-3.64 (m, 1 H), 3.70-3.80 (m, 1 H), 5.29 (q, J = 12.78 Hz, 2 H), 7.28-7.41 (m, 6 H), 7.42-7.50 (m, 4 H). Compound 9: 0.95 (s, 6 H), 2.65 (s, 3 H), 3.77 (s, 2 H), 4.79 (s, 1 H), 5.21 (s, 2 H), 7.23 (d, J = 7.43 Hz, 2 H), 7.27-7.33 (m, 1 H), 7.37 (q, J = 7.50 Hz, 3 H), 7.42-7.47 (m, 2 H), 7.50 (t, J = 7.73 Hz, 2 H). Compound 10: 0.74 (t, J = 7.53 Hz, 3 H), 0.82-0.93 (m, 1 H), 1.02 (s, 3 H), 1.23-1.43 (m, 2 H), 2.72 (s, 3 H), 3.68-3.89 (m, 2 H), 5.30-5.33 (m, 2 H), 7.21-7.27 (m, 3 H), 7.29-7.37 (m, 3 H), 7.42-7.53 (m, 4 H). Compound 11: 1.05 (d, J = 6.1 Hz, 3 H), 1.41 (d, J = 7.2 Hz, 3 H), 2.12 (d, J = 3.3 Hz, 1 H), 3.75-3.85 (m, 1 H), 2.70 (s, 3 H), 3.87-3.97 (m, 1 H), 5.29 (s, 2 H), 7.22-7.29 (m, 3 H), 7.29-7.35 (m, 2 H), 7.35-7.42 (m, 1 H), 7.42-7.51 (m, 4 H).
34. Overman, L. E.; Flippin, L. A. Tetrahedron Lett. 1981, 22, 195.
35. 3, see: Schreiber, S. L. J. Am. Chem. Soc. 1980, 102, 6163.
36. (a) Chini, M.; Croti, P.; Macchia, F. Tetrahedron Lett. 1990, 31, 4661.
37. (b) Schoffers, E.; Tran, S. D.; Mace, K. Heterocycles 2003, 60, 769.
38. (c) Saladino, R.; Ciambecchini, U.; Hanessian, S. Eur. J. Org. Chem. 2003, 4401.