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S. Chandrasekhar et al. / Tetrahedron 62 (2006) 12098–12107
OCH3), 3.40–3.09 (m, 1H, NCH), 2.90–2.50 (m, 5H, NCH,
ArCH2, CH2CO2Et), 1.45 (s, 9H, Boc), 1.35 (t, J¼7.3 Hz,
3H, OCH2CH3); FABMS: m/z 455 (M+); Anal. Calcd for
C26H33NO6: C, 68.55; H, 7.30; N, 3.07. Found: C, 68.32;
H, 7.19; N, 3.19; mp 105 ꢁC; IR (KBr): 2977, 1693, 1620,
(2ꢂ10 mL). The combined organic layers were washed with
brine, dried over Na2SO4 and concentrated under reduced
pressure. The crude compound was purified by silica gel
column chromatography to give the product 4 (0.40 g, 70%).
1259 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 7.60–7.10 (m, 5H, Ph), 6.90
(s, 1H, Ar), 6.75 (s, 1H, Ar), 5.30–5.10 (m, 2H, CH2Ph), 4.35
(q, J¼7.5 Hz, 2H, OCH2CH3), 4.28–4.10 (m, 1H, CH2OH),
3.90–3.59 (m, 5H, OCH3, CH2OH, CH2NH), 3.30–2.40 (m,
3H, CH2NH, ArCH2), 2.15–1.85 (m, 2H, CH2CH2OH), 1.45
(s, 9H, Boc), 1.35 (t, J¼7.5 Hz, 3H, OCH2CH3) 0.90 (s, 9H,
SiCH(CH3)3), 0.10 (s, 6H, Si(CH3)2); FABMS: m/z 600
(M++1), 599 (M+), 600 (M+ꢀ1); Anal. Calcd for
C33H49NO7Si: C, 66.08; H, 8.23; N, 2.34. Found: C,
66.17; H, 8.12; N, 2.42; IR (KBr): 2945, 1692, 1520,
4.1.27. 6-Benzyloxy-1-(2-hydroxy-ethyl)-7-methoxy-3,4-
dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl
ester (34). To a stirred solution of LiCl (0.28 g, 6.5 mmol)
and sodiumborohydride (0.25 g, 6.5 mmol) in ethanol
(20 mL) was added ester 33 (1.0 g, 2.1 mmol) in THF
(20 mL) at 0 ꢁC. The reaction mixture was stirred at room
temperature for 12 h. After completion of the reaction,
solvent was removed under reduced pressure. Reaction mix-
ture was quenched with saturated ammonium chloride and
extracted with EtOAc (2ꢂ30 mL). The combined organic
layers were washed with brine, dried over anhydrous sodium
sulfate, and concentrated under reduced pressure and the
crude product was purified by silica gel chromatography
(hexane–EtOAc 70:30) to yield the alcohol 34 (0.78 g,
87%) as viscous liquid.
1259, 750 cmꢀ1
.
Acknowledgements
N.R.R. and Y.S.R. thank the Council of Scientific and Indus-
trial Research, New Delhi for financial support.
1H NMR (200 MHz, CDCl3): d 7.42–7.25 (m, 5H, Ph), 6.65
(s, 1H, Ar), 6.54 (s, 1H, Ar), 5.23–5.17 (m, 1H, ArCHN),
5.07 (s, 2H, CH2Ph), 4.11–3.96 (m, 2H, CH2OH), 3.85 (s,
3H, OCH3), 3.70–3.42 (m, 2H, CH2NH), 3.14–3.04 (m,
1H, ArCH2), 2.85–2.73 (m, 1H, ArCH2), 2.59–2.50 (m,
1H, CH2CH2OH), 2.10–2.00 (m, 1H, CH2CH2OH), 1.45
(s, 9H, Boc); Anal. Calcd for C24H31NO5: C, 69.71; H,
7.56; N, 3.39. Found: C, 69.67; H, 7.52; N, 3.42; FABMS:
m/z 413 (M+); IR (KBr): 3437, 2933, 1513, 1425,
References and notes
1. (a) Dong, H.; Sheng, J. Z.; Lee, C. M.; Wong, T. M. Br. J.
Pharmacol. 1993, 109, 113; (b) Dong, H.; Lee, C. M.;
Huang, W. L.; Peng, S. X. Br. J. Pharmacol. 1992, 107, 262;
(c) Bernan, V. S.; Montenegro, D. A.; Korshalla, J. D.;
Maiese, W. M.; Steinberg, D. A.; Greenstein, M. J. Antibiot.
1994, 47, 1417; (d) Urverg-Ratsimamanga, S.; Rasoanaivo,
P.; Rafatro, H.; Robijaona, B.; Rakato-Ratsimamanga, A.
Ann. Trop. Med. Parasitol. 1994, 88, 271; (e) Rozwadowska,
M. D. Heterocycles 1994, 39, 903.
2. (a) Wright, A. E.; Forleo, D. A.; Gunawardana, G. P.;
Gunasekera, S. P.; Koehn, F. E.; McConnell, O. J. J. Org.
Chem. 1990, 55, 4508; (b) Rinehart, K. L.; Holt, T. G.;
Fregeau, N. L.; Stroh, J. G.; Keifer, P. A.; Sun, F.; Li, L. H.;
Martin, D. G. J. Org. Chem. 1990, 55, 4512; (c) Rinehart,
K. L.; Holt, T. G.; Fregeau, N. L.; Stroh, J. G.; Keifer, P. A.;
Sun, F.; Li, L. H.; Martin, D. G. J. Org. Chem. 1991, 56,
1676; (d) Sakai, R.; Rinehart, K. L.; Guan, Y.; Wang, A. H. J.
Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 11456; (e) Sakai, R.;
Jares-Erijman, E. A.; Manzanares, I.; Elipe, M. V. S.;
Rinehart, K. L. J. Am. Chem. Soc. 1996, 118, 9017; (f)
Suwanborirux, K.; Charupant, K.; Amnuoypol, S.;
Pummangura, S.; Kubo, A.; Saito, N. J. Nat. Prod. 2002, 65,
935.
3. (a) Ryan, D. P.; Supco, J. G.; Eder, J. P.; Seiden, M. V.; Demetri,
G.; Lynch, T. J.; Fischman, A. J.; Davis, J.; Jimeno, J.; Clark,
J. W. Clin. Cancer Res. 2001, 7, 231; (b) Rinehart, K. L.
Med. Res. Rev. 2000, 20, 1; (c) Reid, J. M.; Walker, D. L.;
Ames, M. M. Cancer Chemother. Pharmacol. 1996, 38, 329;
(d) Erba, E.; Bergamaschi, D.; Bassano, L.; Damia, G.;
Ronzoni, S.; Faircloth, G. T.; D’Incalci, M. Eur. J. Cancer
2001, 37, 97; (e) Erba, E.; Bergamaschi, D.; Bassano, L.;
Ronzoni, S.; Di Liberti, G.; Muradore, I.; Vignati, S.;
Faircloth, G. T.; Jimeno, J.; D’Incalci, M. J. Cancer Res.
2000, 82, 1732; (f) Takebayashi, Y.; Pourquier, P.; Yoshida,
A.; Kohlhagen, G.; Pommier, Y. Proc. Natl. Acad. Sci. U.S.A.
1999, 96, 7196; (g) Moore, R. M., II; Seaman, F. C.;
Wheelhouse, R. T.; Hurley, L. H. J. Am. Chem. Soc. 1998,
1255 cmꢀ1
.
4.1.28. 6-Benzyloxy-1-[2-(tert-butyl-dimethyl-silanyl-
oxy)-ethyl]-7-methoxy-3,4-dihydro-1H-isoquinoline-2-
carboxylic acid tert-butyl ester (35). This compound was
prepared in the same way as aldehyde 22, from the alcohol
34 (0.7 g, 1.69 mmol). The crude material was purified by
silica gel chromatography to afford 35 (0.732 g, 82%) as
thick liquid.
1H NMR (200 MHz, CDCl3): d 7.44–7.20 (m, 5H, Ph), 6.60
(s, 1H, Ar), 6.55 (s, 1H, Ar), 5.20–4.98 (m, 3H, ArCHN,
CH2Ph), 4.20–3.60 (m, 6H, OCH3, CH2OH, CH2NH),
3.30–2.98 (m, 1H, CH2NH), 2.95–2.60 (m, 1H, ArCH2),
2.58–2.45 (m, 1H, ArCH2), 2.08–1.80 (m, 2H, CH2CH2OH),
1.45 (s, 9H, Boc), 0.92 (s, 9H, SiCH(CH3)3), 0.02 (s, 6H,
Si(CH3)2); Anal. Calcd for C30H45NO5Si: C, 68.27; H,
8.59; N, 2.65. Found: C, 68.24; H, 8.55; N, 2.61; FABMS:
m/z 527 (M+).
4.1.29. 6-Benzyloxy-1-[2-(tert-butyl-dimethyl-silanyl-
oxy)-ethyl]-7-methoxy-3,4-dihydro-1H-isoquinoline-2-
dicarboxylic acid-2-tert-butyl ester-1-ethyl ester (4). To
a stirred solution of compound 35 (0.5 g, 0.94 mmol), in
THF (10 mL) at ꢀ78 ꢁC under inert atmosphere was added
n-butyl lithium (0.093 g, 1.3 mmol). The mixture was stirred
at ꢀ78 ꢁC for 15 min and ethyl chloroformate (0.136 mL,
1.3 mmol) was added drop wise. Stirring was continued
for 2 h at the same temperature and allowed to warm to
room temperature. Reaction mixture was quenched with
saturated NH4Cl and extracted with diethyl ether twice