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D.H. Nadkarni et al. / Tetrahedron 69 (2013) 4105e4113
column chromatography over Si gel using EtOAc/hexanes (1:4) as
eluent to yield the pure product, 14 (0.028 g, 76%).
was added and the reaction mixture was refluxed for 40 h. TLC
examination (EtOAc/hexanes, 1:1) revealed that the reaction was
complete. The reaction mixture was then allowed to attain room
temperature and the solvent was evaporated off in vacuo. The res-
idue obtained was dissolved in EtOAc (100 mL), washed with satu-
rated NaHSO3 (2ꢁ50 mL), water (2ꢁ50 mL), brine (1ꢁ50 mL), and
dried over anhydrous Na2SO4. The drying agent was removed by
filtration and the solvent was removed to obtain the crude product,
which was purified by column chromatography over Si gel using
EtOAc/hexanes (1:3) as eluent to furnish the product 17 as an orange
Method B: Alternatively, NaN3 (0.004 g, 0.06 mmol) was added
to a solution of compound 13 (0.025 g 0.041 mmol) in anhydrous
DMF (1 mL), and the reaction mixture was stirred for 4 h at room
temperature. The reaction was quenched with water and extracted
with EtOAc (2ꢁ10 mL). The EtOAc extract was washed with water
(3ꢁ10 mL), brine (1ꢁ10 mL), and dried over anhydrous Na2SO4. The
drying agent was filtered and the solvent was evaporated off. The
residue obtained was purified by column chromatography over Si
gel using EtOAc/hexane (1:4) to yield the pure product, 14 (0.014 g,
solid (0.693 g, 72%); mp 193e194 ꢀC; 1H NMR (CDCl3)
d 1.38 (s, 9H),
74%); mp 236e237 ꢀC; 1H NMR (CDCl3)
d
5.10 (s, 2H), 5.64 (s, 2H),
2.42 (s, 3H), 2.98 (t, 2H, J¼6.4 Hz), 3.38 (q, 2H, J¼6.4 Hz), 4.76 (br s,
1H), 5.08 (s, 2H), 5.55 (s, 2H), 6.78 (s, 1H), 6.97 (d, 2H, J¼8.8 Hz),
7.15e7.45 (m, 12H), 7.50 (d, 2H, J¼8.4 Hz), 7.57 (s, 1H), 7.97 (d, 2H,
6.62 (t, 1H, J¼2.7 Hz), 6.87 (s, 1H), 6.97 (d, 2H, J¼9.0 Hz), 7.30e7.50
(m, 11H), 7.60 (d, 2H, J¼9.0 Hz), 9.53 (br s, 1H); 13C NMR (CDCl3)
d
52.3, 70.1, 108.8, 114.4, 124.3, 124.4, 125.4, 127.3, 127.4, 127.5, 128.0,
J¼8.4 Hz); 13C NMR (CDCl3)
d 21.8, 25.8, 28.4, 40.6, 52.2, 70.0, 79.1,
128.1 (2C), 128.4, 128.6, 128.9, 130.2, 130.3, 132.1, 136.4, 137.1, 158.5,
169.6, 179.6; MS (ESþ) m/z 459 (MþH); HRMS calcd for C30H22N2O3
[M]þ: 458.1630, found 458.1646.
114.4, 122.8, 123.3, 125.1, 126.4, 127.5 (2C), 127.9, 128.0, 128.4, 128.6
(3C), 128.7, 129.0, 129.4, 129.9 (2C), 130.0, 131.1, 134.2, 136.2, 137.0,
145.5, 156.0, 158.5, 167.0, 180.4; MS (ESþ) m/z 756 (MþH) and HRMS
calcd for C39H32N3O5S [MꢂC4H9CO2]þ 654.2063, found 654.2061.
4.7. 3-(4-Hydroxyphenyl)-1H,7H-pyrrolo[3,2-f]indole-4,
8-dione (5)
4.10. N-{2-[7-Benzyl-5-(4-benzyloxyphenyl)-4,8-dioxo-1-(to-
syl)-1,4,7,8-tetrahydro-pyrrolo[3,2-f]indol-3-yl]-ethyl}-N-
methyl-carbamic acid tert-butyl ester (18) and N-{2-(7-benzyl-
5-(4-benzyloxy-phenyl)-1-methyl-4,8-dioxo-1,4,7,8-
tetrahydro-pyrrolo[3,2-f]indol-3-yl]-ethyl}-N-methyl-carba-
mic acid tert-butyl ester (19)
To a solution of compound 14 (0.015 g, 0.033 mmol) in EtOH
(15 mL), HCOONH4 (0.050 g, 0.8 mmol) and Pd black (0.03 g,
0.28 mmol) were added and the reaction mixture was refluxed for
15 h. TLC examination (CHCl3/MeOH, 20:1) revealed that the reaction
is complete. The reaction mixture was then allowed to attain room
temperature and filtered through a pad of Celite 585 and washed
with EtOAc/CHCl3 (1:1). The combined filtrate and washings were
evaporated in vacuo. The residue obtained was dissolved in EtOAc
(10 mL) and washed with water (2ꢁ5 mL), brine (1ꢁ5 mL), and dried
over anhydrous Na2SO4. The drying agent was removed by filtration
and the solvent was evaporated off in vacuo to obtain the crude
product, which was purified by column chromatography over Si gel
using MeOH/CHCl3 (1:25) as eluent to furnish the pure product 5
To a solution of compound 17 (0.3 g, 0.4 mmol) in anhydrous
DMF (3 mL), NaH (0.032 g, 0.8 mmol, 60% dispersion in mineral oil)
was added at 0 ꢀC. The reaction mixture was stirred for 30 min
followed by addition of CH3I (0.25 g, 1.75 mmol). The temperature
was gradually increased to room temperature and stirred for 30 h.
TLC examination (EtOAc/hexanes, 1:1) revealed that the reaction
was complete. The reaction mixture was quenched with saturated
solution of NH4Cl and extracted with EtOAc (100 mL). The EtOAc
extract was further washed with water (3ꢁ40 mL), brine
(1ꢁ40 mL), and dried over Na2SO4. The drying agent was filtered off
and the solvent was evaporated off to obtain the crude product,
which was purified by column chromatography over Si gel using
EtOAc/hexanes (1:1) as eluent to afford pure compounds 18
(0.141 g, 46%) and 19 (0.085 g, 34%) as orange and yellow solids.
(0.0046 g, 50%); 1H NMR (CD3OD)
d
6.54 (d,1H, J¼2.7 Hz), 6.79 (d, 2H,
J¼8.7 Hz), 7.01 (d,1H, J¼2.7 Hz), 7.04 (s,1H), 7.55 (d, 2H, J¼8.7 Hz); 13C
NMR (CD3OD)
d 109.3, 115.6, 123.3, 124.6, 126.1, 126.2, 129.2, 130.0,
131.1, 132.9, 134.9, 157.9, 169.8, 182.5; MS (ESþ) m/z 279 (MþH), 277
(MꢂH); HRMS calcd for C16H10N2O3 [M]þ 278.0691, found 278.0700.
4.8. tert-Butyl-2-(6-(benzylamino)-4,7-dihydro-4,7-dioxo-1-
tosyl-1H-indol-3-yl)ethylcarbamate (16)
Compound 18: mp 165e166 ꢀC; 1H NMR (CDCl3)
d 1.30e1.50 (m,
9H), 2.41 (s, 3H), 2.83 (s, 3H), 2.89e3.11 (m, 2H), 3.5 (t, 2H,
J¼7.2 Hz), 5.08 (s, 2H), 5.56 (s, 2H), 6.78 (s, 1H), 6.97 (d, 2H,
J¼8.7 Hz), 7.10e7.55 (m, 13H), 7.52 (d, 2H, J¼8.7 Hz), 7.96 (d, 2H,
To a solution of quinone, 15 (0.77 g, 1.62 mmol) in MeOH/THF
(1:1,150 mL), benzyl amine (0.261 g, 2.43 mmol) was added and the
reaction mixture was stirred at room temperature for 20 h. TLC
examination (EtOAc/hexanes, 1:1) revealed that the reaction was
complete. The solvent was evaporated off in vacuo and the residue
obtained was purified by column chromatography over Si gel using
EtOAc/hexanes (1:4) as eluent to afford the pure aminated product
J¼8.4 Hz); 13C NMR (CDCl3)
d 21.7, 24.2, 28.4, 34.7, 48.4, 52.3, 70.0,
79.3, 114.5, 122.9, 123.4, 125.2, 126.4, 127.4 (2C), 127.9, 128.0, 128.4,
128.6 (2C), 128.8 (2C), 129.0, 129.4, 130.0 (2C), 131.1, 134.4, 136.3,
137.0, 145.5, 155.7, 158.5, 167.1, 180.1; MS (ESþ) m/z 770 (M þ H) and
HRMS calcd for C40H34N3O5S [MꢂC4H9CO2]þ 668.2219, found
668.2215. Compound 19: mp 120e122 ꢀC (dec); 1H NMR (CDCl3)
16 (0.69 g, 78%); mp 154e155 ꢀC; 1H NMR (CDCl3)
d
1.41 (s, 9H), 2.43
d 1.30e1.55 (m, 9H), 2.79 (s, 3H), 2.88e3.07 (m, 2H), 3.46 (t, 2H,
(s, 3H), 2.98 (t, 2H, J¼6.4 Hz), 3.39 (q, 2H, J¼6.4 Hz), 4.23 (d, 2H,
J¼5.6 Hz), 4.87 (br s, 1H), 5.29 (s, 1H), 6.02 (br t, 1H, J¼5.6 Hz), 7.24
(d, 2H, J¼8.4 Hz), 7.30e7.40 (m, 5H), 7.67 (s, 1H), 7.97 (d, 2H,
J¼6.9 Hz), 3.89 (s, 3H), 5.09 (s, 2H), 5.65 (s, 2H), 6.77 (s, 1H), 6.98 (d,
2H, J¼8.7 Hz), 7.21e7.45 (m, 11H), 7.60 (d, 2H, J¼8.7 Hz); 13C NMR
(CDCl3)
d 24.2, 28.4, 34.3, 36.4, 48.9, 52.1, 70.1, 79.0, 114.4, 123.1,
J¼8.4 Hz); 13C NMR (CDCl3)
d
21.8, 25.7, 28.4, 40.5, 47.2, 79.1, 98.0,
124.0, 125.7, 125.8, 126.3, 127.3, 127.5, 127.9, 128.0, 128.1, 128.6,
128.8, 129.4, 130.1, 130.3, 130.7, 136.7, 137.1, 155.8, 158.3, 170.6,
180.5; MS (ESþ) m/z 630 (MþH) and HRMS calcd for C39H39N3O5
629.2890, found 629.2884.
123.6, 127.3, 127.7, 128.1, 128.9 (2C), 129.7, 130.1, 130.6, 133.9, 135.8,
146.1, 147.4, 156.0, 170.2, 183.2; MS (ESþ) m/z 550 (M þ H) and
HRMS calcd for C25H22N3O6S [MꢂC4H9]þ 492.1229, found 492.1227.
4.9. 2-[7-Benzyl-5-(4-benzyloxyphenyl)-4,8-dioxo-1-(tosyl)-
1,4,7,8-tetrahydro-pyrrolo[3,2-f]indol-3-yl]-ethyl-carbamic
acid tert-butyl ester (17)
4.11. N-{2-[5-(4-Hydroxy-phenyl)-1-methyl-4,8-dioxo-1,4,7,8-
tetrahydro-pyrrolo[3,2-f]-indol-3-yl]-ethyl}-N-methyl-carba-
mic acid tert-butyl ester (20)
To a solution of quinone 16 (0.7 g, 1.27 mmol) and acetal, 9
To a solution of compound 19 (0.014 g, 0.022 mmol) in anhy-
(2.66 g, 8.9 mmol) in CH3CN (100 mL), Mn(OAc)3 (2.4 g, 8.9 mmol)
drous EtOH (10 mL), HCOONH4 (0.05 g, 0.8 mmol) and Pd black