B. M. Mathes, S. A. Filla / Tetrahedron Letters 44 (2003) 725–728
727
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Scheme 3. Reagents and conditions: (a) Me3Al, Me2NH·HCl,
CH2Cl2, rt (97%); ii. LiAlH4, THF, 30°C (64%). (b) Benzo-
phenone imine, Pd2(dba)3, ( )-BINAP, NaOt-Bu, toluene,
80°C; ii. 1N HCl/THF (1:1), rt (88%, two steps). (c) 4-Fluoro-
benzoyl chloride, pyridine, 55°C (96%).
5. (a) Hickson, C. L.; NcNab, H. Synthesis 1981, 464–465;
(b) Shiotani, S.; Morita, H. Heterocyclic Chem. 1986, 23,
665–668.
was converted to the N,N-dimethylaminoethyl side
chain in two steps, which included amide formation
using Weinreb’s protocol,15 followed by LiAlH4 reduc-
tion to provide 11. Conversion of the C-5 chloro group
of 11 to the corresponding amine through a Pd-cata-
lyzed amination reaction, employing benzophenone
imine as an ammonia equivalent,16 followed by acid
hydrolysis, generated primary amine 12. Acylation of
12 subsequently provided target compound 4.
6. Reviews: (a) Hegedus, L. S. Angew. Chem. Int. Ed. 1988,
27, 1113–1126; (b) Sakamoto, T.; Kondo, Y.; Yamanaka,
H. Heterocycles 1988, 27, 2225–2249.
7. (a) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991,
113, 6689–6690; (b) Larock, R. C.; Yum, E. K.; Doty, M.
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8. (a) Jeschke, T.; Wensbo, D.; Annby, U.; Gronowitz, S.
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The Pd(0)-catalyzed intramolecular cyclization of O-
allyl-substituted ortho-iodopyridines provided an
attractive method to prepare 2,3-disubstituted furo[3,2-
b]pyridines. We believe that this method is general and
can be applied to the synthesis of other disubstituted
heterobicyclic ring systems. Using this approach, we
efficiently prepared 5-HT1F receptor agonist 4. The
biological activity of this compound will be described
elsewhere in due course.
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