F. Hadjaz et al. / Tetrahedron 64 (2008) 10004–10008
10007
4.4.6. 2-(3,4,5-Trimethoxybenzyl)tryptamine hydrochloride (3f)
H7, J¼8.3 Hz), 7.35 (s, 1H, H4), 9.00 (br s, 2H, NHþ2 ), 9.30 (br s, 1H,
Yield 80%; maroon solid, mp 140–142 ꢀC; 1H NMR (300 MHz,
OH), 10.80 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6)
d
¼11, 17, 19,
DMSO-d6)
d¼2.90 (m, 2H, CH2), 3.10 (m, 2H, CH2), 3.60 (s, 3H,
21, 29, 32, 47, 48,106,111,113,115,116,119,121,128,130,134.1,134.5,
OCH3), 3.75 (s, 6H, OCH3), 4.10 (s, 2H, CH2), 6.70 (s, 2H, HAr), 7.00 (m,
2H, H5, H6), 7.30 (d, 1H, H7, J¼7.6 Hz), 7.50 (d, 1H, H4, J¼7.6 Hz), 8.20
(br s, 3H, NHþ3 ), 11.05 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6)
136, 141, 158; mass m/z 337.2 (Mþþ1).
4.5. Description of naphthyridine compounds 4b, 4e, and 4i
d
¼20, 33, 56, 56.5, 57, 61,105,108,111,113,117,118,119,121,128,133,
135, 145, 153, 162; mass m/z 341.2 (Mþþ1).
To a solution of compounds 2b, 2e, and 2i (10 mmol) in MeOH
(50 mL) were added HCO2NH4 (4.5 g, 100 mmol) and Pd/C
(100 mg). The resulting solution was refluxed for 2 h and then
evaporated. The obtained residue was triturated with a 5% K2CO3
aqueous solution (30 mL) and extracted with CH2Cl2. The organic
layer was dried over magnesium sulfate and evaporated to dryness
under reduced pressure. The crude product was purified by column
chromatography using dichloromethane–methanol (90:10, v/v) as
eluent to afford compounds 4b, 4e, and 4i.
4.4.7. 5-Ethyl-2-(3,5-di-tert-butyl-4-hydroxybenzyl)tryptamine
hydrochloride (3g)
Yield 77%; maroon solid, mp 112–113 ꢀC; 1H NMR (300 MHz,
CDCl3)
d
¼1.20 (t, 3H, CH3, J¼7.6 Hz), 1.35 (s, 18H, CH3), 2.60 (q, 2H,
CH2, J¼7.6 Hz), 3.80 (m, 2H, CH2), 3.90 (m, 2H, CH2), 3.90 (s, 2H,
CH2), 6.90 (dd, 1H, H6, J¼8.2, 1.6 Hz), 7.00 (s, 2H, HAr), 7.15 (d, 1H, H7,
J¼8.2 Hz), 7.25 (s, 1H, H4), 10.65 (s, 1H, NH); 13C NMR (300 MHz,
CDCl3)
d
¼16, 25, 29, 30, 32, 34, 41, 107, 110, 116, 121, 125, 125.3,
128.6, 128.8, 134, 135.4, 135.7, 136, 136.3, 152; mass m/z 407.4
(Mþþ1).
4.5.1. 1-(4-Methylphenyl)-5,10-dihydro-benzo[b][1,7]-
naphthyridine (4b)
Yield 36%; maroon solid, mp 95–96 ꢀC; 1H NMR (300 MHz,
4.4.8. 5-Ethyl-2-(3-hydroxybenzyl)tryptamine hydrochloride (3h)
CDCl3)
d
¼2.50 (s, 3H, CH3), 7.35 (m, 1H, H7), 7.40 (d, 2H, HAr
,
Yield 75%; green solid, mp 178–180 ꢀC; 1H NMR (300 MHz,
J¼8.1 Hz), 7.55 (m, 2H, H8, H9), 7.85 (d, 2H, HAr, J¼8.1 Hz), 7.95 (d,
DMSO-d6)
d
¼1.2 (t, 3H, CH3, J¼7.6 Hz), 2.6 (q, 2H, CH2, J¼7.6 Hz),
1H, H4, J¼5.2 Hz), 8.20 (d, 1H, H6, J¼7.9 Hz), 8.55 (d, 1H, H3,
J¼5.2 Hz), 8.65 (br s, 1H, NH); 13C NMR (300 MHz, DMSO-d6)
d¼21,
2.85 (m, 2H, CH2), 3.00 (m, 2H, CH2), 3.95 (s, 2H, CH2), 6.60 (m, 2H,
H
Ar), 6.70 (d, 1H, HAr, J¼7.7 Hz), 6.90 (dd, 1H, H6, J¼8.2, 1.9 Hz), 7.05
113, 114, 119.9, 120.8, 121.3, 122, 128.5, 128.7, 129.2, 129.4, 129.8, 133,
136, 138.4, 138.8, 141, 143; mass m/z 259.1 (Mþþ1).
(t, 1H, HAr, J¼7.9, 7.6 Hz), 7.20 (d, 1H, H7, J¼8.2 Hz), 7.30 (s, 1H, H4),
8.10 (br s, 3H, NHþ3 ), 9.35 (s, 1H, OH), 10.80 (s, 1H, NH); 13C NMR
(300 MHz, DMSO-d6)
d
¼21, 23, 31, 35, 51, 108, 111, 112, 114, 116, 119,
122, 128, 131, 132, 133, 136, 142, 156; mass m/z 295.2 (Mþþ1).
4.5.2. 1-(3,4-Dimethoxyphenyl)-5,10-dihydro-benzo[b][1,7]-
naphthyridine (4e)
Yield 41%; beige solid, mp 104–105 ꢀC; 1H NMR (300 MHz,
4.4.9. 2-(3-Hydroxybenzyl)tryptamine (3i)
Yield 78%; green solid, mp 70–72 ꢀC; 1H NMR (300 MHz, DMSO-
CDCl3)
d
¼3.95 (s, 3H, OCH3), 4.00 (s, 3H, OCH3), 6.90 (d, 1H, HAr
,
J¼7.9 Hz), 7.35 (m, 1H, H7), 7.55 (m, 4H, H8, H9, HAr), 7.95 (d, 1H, H4,
J¼4.7 Hz), 8.20 (d, 1H, H6, J¼8.1 Hz), 8.55 (d, 1H, H3, J¼4.7 Hz), 9.10
d6)
d
¼1.80 (br s, 2H, NH2), 2.70 (m, 2H, CH2), 2.90 (m, 1H, CH2), 3.30
(m, 1H, CH2), 3.95 (s, 2H, CH2), 6.60 (m, 2H, HAr), 6.70 (d, 1H, HAr
,
(s, 1H, NH); 13C NMR (300 MHz, CDCl3)
d
¼56, 58, 111, 111.3, 111.5,
J¼6.6 Hz), 7.00 (m, 3H, H5, H6, HAr), 7.25 (d, 1H, H7, J¼8.2 Hz), 7.45
(d, 1H, H4, J¼7.6 Hz), 10.75 (s, 1H, NH); 13C NMR (300 MHz, DMSO-
112,113,120,120.3,121,128,130, 131,133,139, 140, 143, 149.5,149.7;
mass m/z 305.2 (Mþþ1).
d6)
d
¼26, 32, 52, 109, 111, 113, 115, 118.3, 118.6, 119, 120, 128, 129,
135, 136, 142, 158, 166; mass m/z 267.3 (Mþþ1).
4.5.3. 1-(3-Hydroxyphenyl)-5,10-dihydro-benzo[b][1,7]-
naphthyridine (4i)
4.4.10. 2-(4-Methoxycarbonylbenzyl)tryptamine (3j)
Yield 23%; green solid, mp 96–98 ꢀC; 1H NMR (300 MHz, DMSO-
Yield 83%; maroon solid, mp 150–151 ꢀC; 1H NMR (300 MHz,
d6)
d
¼6.90 (m, 1H, HAr), 7.25 (t, 1H, HAr, J¼7.0 Hz), 7.45 (m, 3H, HAr),
CDCl3)
d
¼2.90 (m, 4H, CH2), 3.80 (br s, 2H, NH2), 3.90 (s, 3H, OCH3),
7.55 (m,1H, HAr), 7.65 (d,1H, H9, J¼8.2 Hz), 8.10 (d,1H, H4, J¼5.1 Hz),
4.10 (s, 2H, CH2), 7.10 (m, 2H, HAr), 7.20 (m, 3H, HAr), 7.50 (d, 1H, H5,
J¼8.4 Hz), 7.90 (d, 2H, HAr, J¼8.0 Hz), 8.30 (s, 1H, NH); 13C NMR
8.25 (d, 1H, H6, J¼8.2 Hz), 8.40 (d, 1H, H3, J¼5.1 Hz), 9.60 (br s, 1H,
OH), 11.50 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6)
d
¼113, 114,
(300 MHz, CDCl3)
d
¼32, 41, 52, 64, 108, 110, 118, 119, 121, 128.1,
115, 116, 119.5, 119.9, 121, 122, 128, 129, 130, 133, 138, 140, 141, 142,
128.5, 128.6, 130, 133, 135, 144, 154, 162, 167; mass m/z 309.1
(Mþþ1).
158; mass m/z 261.1 (Mþþ1).
Acknowledgements
4.4.11. 5-Ethyl-2-(3-methoxybenzyl)-N-propyl tryptamine (3k)
Yield 85%; beige solid, mp 85–86 ꢀC; 1H NMR (300 MHz, CDCl3)
´
The 300 MHz NMR facilities were funded by the Region Nord-
d
¼0.90 (t, 3H, CH3, J¼7.4 Hz), 1.30 (t, 3H, CH3, J¼7.1 Hz), 1.60 (m, 2H,
`
Pas de Calais (France), the Ministere de la Jeunesse, de l’Education
Nationale et de la Recherche (MJENR), and the Fonds Europeens de
CH2), 2.50 (m, 2H, CH2), 2.70 (m, 4H, CH2), 3.00 (m, 2H, CH2), 3.75 (s,
3H, OCH3), 4.10 (s, 2H, CH2), 5.00 (br s, 1H, NH), 6.75 (m, 3H, HAr),
7.00 (dd, 1H, HAr, J¼8.6, 1.6 Hz), 7.20 (m, 2H, HAr), 7.40 (d, 1H, H4,
´
De´veloppement Re´gional (FEDER).
J¼6.9 Hz), 7.80 (s, 1H, NH); 13C NMR (300 MHz, CDCl3)
¼12, 17, 18,
d
References and notes
19, 23, 28, 31, 52, 54, 105, 111, 112, 113, 117, 120, 122, 127, 131, 134,
135, 136, 143, 157; mass m/z 351.6 (Mþþ1).
1. Saxton, J. E. Indoles; Wiley-Interscience: New York, NY, 1983; Part 4.
2. Sundberg, R. J. Indoles; Academic: London, 1996.
3. Maruoka, K.; Oishi, M.; Yamamoto, H. J. Org. Chem. 1993, 58, 7638.
4. Tokuyama, H.; Yamashita, T.; Reding, M. T.; Kaburagi, Y.; Fukuyama, T. J. Am.
Chem. Soc. 1999, 121, 3791.
5. Labadie, S. S.; Teng, E. J. Org. Chem. 1994, 59, 4250.
6. Chu, L.; Fisher, M. H.; Goulet, M. T.; Wyvratt, M. J. Tetrahedron Lett. 1997, 38,
3871.
4.4.12. 5-Ethyl-2-(3-hydroxybenzyl)-N-propyl tryptamine
hydrochloride (3l)
Yield 82%; beige solid, mp 208–209 ꢀC; 1H NMR (300 MHz,
DMSO-d6)
1.65 (m, 2H, CH2), 2.60 (q, 2H, CH2, J¼7.4 Hz), 2.85 (m, 2H, CH2), 3.10
(m, 2H, CH2), 3.40 (m, 2H, CH2), 4.00 (s, 2H, CH2), 6.60 (dd, 1H, HAr
d¼0.90 (t, 3H, CH3, J¼7.4 Hz), 1.20 (t, 3H, CH3, J¼7.0 Hz),
7. Lane, B. S.; Sames, D. Org. Lett. 2004, 6, 2897.
,
8. Toure´, B. B.; Lane, B. S.; Sames, D. Org. Lett. 2006, 8, 1979.
9. Lane, B. S.; Brown, M. A.; Sames, D. J. Am. Chem. Soc. 2005, 127, 8050.
10. Wang, X.; Lane, B. S.; Sames, D. J. Am. Chem. Soc. 2005, 127, 4996.
J¼7.4, 1.7 Hz), 6.60 (d, 1H, HAr, J¼1.7 Hz), 6.70 (d, 1H, HAr, J¼7.4 Hz),
6.90 (dd, 1H, H6, J¼8.3, 1.4 Hz), 7.05 (t, 1H, HAr, J¼7.7 Hz), 7.20 (d, 1H,