Synthesis of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular nitrilimine cycloaddition

Tetrahedron Letters

Volumn 55, Issue 13, 2014, Pages 2150-2153

  Winters, Michael P ^a   Teleha, Christopher A ^a   Sui, Zhihua ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

N type Calcium Channel; Nitrilimine; Tetrahydrocyclopentylpyrazoles; Tetrahydropyrrolopyrazoles

Indexed keywords

2,4,5,6 TETRAHYDROCYCLOPENTA[C]PYRAZOLE DERIVATIVE; 2,4,5,6 TETRAHYDROPYRROLO[3,4 C]PYRAZOLE DERIVATIVE; ALKYNE DERIVATIVE; ALKYNYLBROMIDE DERIVATIVE; BROMINE DERIVATIVE; IMINE; NITRILIMINE; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CYCLIZATION; CYCLOADDITION; DRUG STRUCTURE; DRUG SYNTHESIS; REACTION ANALYSIS; REPRODUCIBILITY; STEREOISOMERISM;

EID: 84896545978     PISSN: 00404039     EISSN: 18733581     Source Type: Journal    
DOI: 10.1016/j.tetlet.2014.02.068     Document Type: Article

References (14)

1. T. Aubert, B. Tabyaoui, M. Farnier, and R. Guilard Synthesis 1988 742
2. T. Yamamoto, and A. Takahara Curr. Top. Med. Chem. 9 2009 377
3. S. Fustero, A. Simon-Fuentes, and J.F. Sanz-Cerveram Org. Prep. Proced. Int. 41 2009 253
4. J.-Y. Yoon, S. Lee, and H. Shin Curr. Org. Chem. 15 2011 657
5. K. Makino, H.S. Kin, and Y. Kurasawa J. Heterocycl. Chem. 35 1998 489
6. S. Kumar, S. Yadav, B. Raghava, B. Saraiah, H. Ila, K. Rangappa, and A. Hazra J. Org. Chem. 78 2013 4960
7. G. Broggini, G. Molteni, and G. Zecchi Heterocycles 47 1998 541
8. B.M. Trost, Z.T. Ball, and K.M. Laemmerhold J. Am. Chem. Soc. 127 2005 10028
9. P. Wolkoff Can. J. Chem. 53 1975 1333
10. A. Padwa, S. Nahm, and E. Sato J. Org. Chem. 43 1978 1664
11. G. Molteni Heterocycles 63 2004 1423
12. These were single reactions and are unoptimized. Perhaps the electron-donating effects of the substituents commonly used (necessary for N-type calcium channel activity) destabilize the nitrilimine intermediate, while neutral phenyl stabilizes it and thus encourages the cyclization at rt. Or perhaps the ortho-substituent twists the aryl out of plane from the nitrilimine destabilizing it, while the phenyl remains in the plane and stabilizes the nitrilimine by delocalizing the charge.
13. J. Leroy Synth. Commun. 22 1992 567
14. L. Brandsma, and H.D. Verkruijsse Synthesis 11 1990 984