A novel and convenient method for the synthesis of substituted naphthostyrils

Tetrahedron Letters

Volumn 44, Issue 12, 2003, Pages 2545-2548

  Liu, Jin Jun ^a   Konzelmann, Fred ^a   Luk, Kin Chun ^a  

^a HOFFMANN LA ROCHE INC   (United States)

Author keywords

CDK2 inhibition; Cross coupling; Intramolecular cyclization; Naphthostyril

Indexed keywords

3 PYRROLYL 6 FLUORONAPHTHOSTYRIL; CYCLIN DEPENDENT KINASE INHIBITOR; OXINDOLE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CATALYST; CYCLIZATION; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROGENATION; OXIDATION;

EID: 0037450923     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00292-2     Document Type: Article

References (24)

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2. For review articles on CDKs inhibitors, see: (a) Steinman, R. A. Oncogene 2002, 21, 3403-3413; (b) Sherr, C. Science 1996, 274, 1672-1677; (c) Morgan, D. Nature 1995, 374, 131-134; (d) Hunter, T.; Pines, J. Cell 1994, 79, 573-582 and references cited therein.
3. For review articles on CDKs inhibitors, see: (a) Steinman, R. A. Oncogene 2002, 21, 3403-3413; (b) Sherr, C. Science 1996, 274, 1672-1677; (c) Morgan, D. Nature 1995, 374, 131-134; (d) Hunter, T.; Pines, J. Cell 1994, 79, 573-582 and references cited therein.
4. For review articles on CDKs inhibitors, see: (a) Steinman, R. A. Oncogene 2002, 21, 3403-3413; (b) Sherr, C. Science 1996, 274, 1672-1677; (c) Morgan, D. Nature 1995, 374, 131-134; (d) Hunter, T.; Pines, J. Cell 1994, 79, 573-582 and references cited therein.
5. For small molecular weight CDK inhibitors, see recent review articles: (a) Hardcastle, I. R.; Golding, B. T.; Griffin, R. J. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 325-348; (b) Sielecki, T. M.; Boylan, J. F.; Benfield, P. A.; Trainor, G. L. J. Med. Chem. 2000, 43, 1-18; (c) Gray, N.; Detivaud, L.; Doerig, C.; Meijer, L. Curr. Med. Chem. 1999, 6, 859-875; (d) Sedlacek, H. H.; Czech, J.; Naik, R.; Kaur, G.; Worland, P., et al., Int. J. Oncol. 1996, 9, 1143-68 and references cited therein.
6. For small molecular weight CDK inhibitors, see recent review articles: (a) Hardcastle, I. R.; Golding, B. T.; Griffin, R. J. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 325-348; (b) Sielecki, T. M.; Boylan, J. F.; Benfield, P. A.; Trainor, G. L. J. Med. Chem. 2000, 43, 1-18; (c) Gray, N.; Detivaud, L.; Doerig, C.; Meijer, L. Curr. Med. Chem. 1999, 6, 859-875; (d) Sedlacek, H. H.; Czech, J.; Naik, R.; Kaur, G.; Worland, P., et al., Int. J. Oncol. 1996, 9, 1143-68 and references cited therein.
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15. Protection of the oxindole is necessary for the subsequent cross-coupling reaction. Coupling of the unprotected oxindole 6 with 9 under the same conditions gave only a trace of the desired product 20a. The major product was the oxidized diketone 20b.
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20. In our early study, the cis-olefin 21, obtained by partial hydrogenation of 10 using Lindlar catalyst followed by deprotection with TFA, readily cyclized to form 13 when treated with base as expected.
21. NaH gave the best result of the bases tried in the reaction including KH, KOH, and organic bases.
22. Liu, J. J.; Luk, K. C.; Konzelmann, F. unpublished data.
23. +) calcd: 312.0910, found: 312.0909.
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