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71 (s, 3H), 3.68 (s, 8H) 13 C NMR (CDCl 3 ): l 158 MS (EI) m/z (rel. int 6b (320 mg, 50%). 1 H NMR (CDCl 3 ): l 7 (s, 3H), 3.63 (s, 8H). 13 C NMR (CDCl 3 ): l 158, 3H), 7.53 (t, J=7.5 Hz, 1H) 41%). 1 H NMR (CDCl 3 ): l 7 1H), 6.72 (d, J=7.4 Hz, 1H), pp.9262-34781 ,
62 (s, 8H) 13 C NMR (CDCl 3 ): l 158, p.74 ,
13 C NMR (CDCl 3 ): l 158 MS (EI) m/z (rel. int.): 301 (13 (s, 9H), 7c (300 mg, 50%). 1 H NMR (CDCl 3 ): l 7.42 (t, J=8.2 Hz, 1H), 6.84 (d, J=7.6 Hz, 1H), 6.59, pp.5593-199 ,
2-Pyridyl)-4-trityl-1-piperazine (1) Column chromatography (70/30 hexane/AcOEt) yielded 23.3 g (94%) of 1 as a light yellow solid Mp: 200 8C. NMR 1 H (CDCl 3 ): dZ2.42 (s, 4H), 3.64 (s, 4H) (3-Pyridyl)-4-trityl-1-piperazine (2) Column chromatography, AcOEt) yielded 22 g (88%) of 2 as a light yellow solid. NMR 1 H (CDCl 3 ): dZ 2.47 (m, 4H), 3.34 (t, JZ4.8 Hz, 4H) JZ3.1 Hz, 1H), pp.12-19 ,
First selective lithiation of pyridylpiperazines: straightforward access to potent pharmacophores, Tetrahedron, vol.61, issue.20, pp.4761-4768, 2005. ,
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NMR 13 C (CDCl 3 ): dZ46 ,
93 (s, 1H)49 (d, JZ7.2 Hz, 6H) NMR 13 C (CDCl 3 ): dZ46, pp.5414-5421 ,
99 (d, JZ6.2 Hz, 1H) NMR 13 C (CDCl 3 ): dZ44, pp.82-243 ,
First selective lithiation of pyridylpiperazines: straightforward access to potent pharmacophores, 1H), 2.97 (t, JZ4.8 Hz, 4H), 3.31 (t, JZ4.8 Hz, 4H), 6.60 (s, 1H), pp.4761-4768, 2005. ,
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18 (s, 1H), 6.47 (s, 1H), 6.55 (s, 1H) NMR 13 C (CDCl 3 ): dZ25 (EI) m/z (rel. int, pp.29-283 ,
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SMe moieties were found stable under BuLi- LiDMAE lithiation conditions See for example Refs. 7a?c and (a) Gros, Ph Eur. J. Org. Chem, vol.4, pp.628-630, 2002. ,
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(7) For a review dedicated to this reagent, see: Gros, Tetrahedron Ph Eur. J. Org. Chem, pp.61-4761, 2002. ,
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(10) a,a¢-Disubstituted pyridines were formed in some cases upon electrophile addition (especially when MeSSMe was used) in the 4-aminopyridine series, p.89831, 2003. ,
General Procedure for Bisfunctionalization of 1, 2 and 3. Under N 2 , n-BuLi (6.40 mL, 16 mmol) was added dropwise to a solution of 2-(dimethylaminoethanol) (0.80 mL, 8 mmol) in toluene (10 mL) at 0 °C. After 15 min of stirring, 1, 2 or 3 (0.24 g, 1 mmol) was added at 0 °C, the mixture was then allowed to warm to 25 °C for isomer 1 or maintained at 0 °C for isomer 2 and 3 and stirred for 3 h. The suspension was then cooled to ?78 °C and was treated with a solution of the appropriate electrophile (10 mmol) in THF (10 mL). The temperature was then maintained at ?78 °C for 1 h and allowed to warm to r, The reaction medium was then evaporated under vacuum and the crude product was purified by chromatography on silica gel, pp.238-7914, 2002. ,
(EI): m/z (rel. int, pp.179-165 ,
Found: C, 57.92; H, 5.87; N, 16.72 Compound 2c: 1 H NMR (CDCl 3 ): d = 3.54 (s, 8 H)86 (s, 2 H), 8.01 (d, J = 6.2 Hz, 2 H) ppm. 13 C NMR (CDCl 3 ): d = 49, (d, J = 6.1 Hz, 2 H) MS (EI): m/z (rel. int.) =, p.61 ,
1 Hz, 1 H) ppm. 13 C NMR (CDCl 3 ): d = 44 (EI): m/z (rel. int, pp.5-398 ,
MS (EI): m/z (rel. int, pp.79-78 ,
59 (s, 1 H), pp.64-70 ,
(EI): m/z (rel. int, pp.15-79 ,