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was stirred at room temperature for 20 min. After that
the solvent was removed under vacuum and dried under
high vacuum. The brown residue was then tritated with
diethyl ether to afford 16, (7 mg, 70% yield) as TFA
zolidine-2040-dione (18). Prepared as 14A, (94%). 1H
NMR (CDCl3) d: 8.74 (bs, 1H), 7.60 (m, 1H), 7.31 (m,
4H), 7.05 (m, 5H), 6.46 (m, J=8.5 Hz, 1H), 625 (s, 1H),
6.11 (m, 1H), 5.07 (d, J=15.4 Hz, 1H), 4.23 (d, J=15.4
Hz, 1H), 3.70 (m, 2H), 3.07 (s, 3H), 2.83 (m, 6H), 2.67
(m, 2H), 1.84 (m, 1H), 1.57 (m, 4H); ESI-MS m/z 524
[M+H]+ and 546 [M+Na]+.
1
salt. H NMR (DMSO) d: 11.02 (s, 1H), 7.57 (d, J=8.0
Hz, 1H), 7.42 (m, 2H), 7.35 (d, J=6.4 Hz, 1H), 7.29 (m,
2H), 7.08 (m, 2H), 6.98 (m, 1H), 6.76 (d, J=6.8 Hz,
1H), 6.11 (dd, J=2.0 and 7.0 Hz, 1H), 4.74 (s, 2H), 4.11
(m, 1H), 3.77 (bs, 1H), 2.75 (m, 2H), 2.70 (m, 4H), 2.26
(m, 1H), 2.17 (m, 1H), 1.77 (m, 2H); MS MS: m/z 538
[M+H]+.
7-(Tolyloxy)-30-40-dihydro-2H-quinoline-10-(1H-indol-3-
yl-methyl)-30-methy-imidazolidine-2040-dione (19A).
mixture of compound 15B, (80 mg, 0.21mmol),
A
Cu(OAc)2 (78 mg, 0.40 mmol), p-tolyl boronic acid (60
mg, 0.44 mmol) and 20 mg of powdered 4 A molecular
sieves in 2 mL of anhydrous CH2Cl2 in a capped vial
was added of triethylamine (58 mL, 0.410 mmol) in an
atmosphere of air The mixture was stirred vigorously at
room temperature for 24 h (during which the color was
observed changing from blue to green) and filtered
through silica bed, washing with CHCl3/MeOH (10:1).
Chromatography of the filtrate on silica gel (Hexane/
EtOAc 3:1) afforded 19A (35% yield). 1H NMR
(CDCl3) d: 8.02 (bs, 1H), 7.69 (m, 1H), 7.32 (m, 5H),
7.08 (m, 2H0, 6.67 (d, J=8.4 Hz, 1H), 6.18 (m, 2H),
5.07 (d, J=15.6 Hz, 1H), 4.25 (d, J=15.5 Hz, 1H), 3.84
(m, 2H), 3.11 (s, 3H), 2.34 (s, 3H), 2.15 (m, 1H), 1.78
(m, 1H); ESI-MS m/z 467 [M+H]+.
7-Phenoxy-3,4-dihydro-2H-quinoline-1-(4-benzylamino-
1yl-butan-1-one)-4-spiro-50-10-(1H-indol-3-ylmethyl)-30-
methyl-imidazolidine-20,40-dione (17B). Prepared as 16,
1
(92%). H NMR (CDCl3) d: 9.77 (bs, 1H), 9.40 (bs,
1H), 8.28 (bs, 1H), 7.60 (m, 1H), 7.37 (m, 12H), 7.12 (m,
1H), 6.94 (d, J=7.8 Hz, 1H), 6.61 (s, 1H), 6.33 (d,
J=7.5 Hz, 1H), 5.83 (m, 1H), 4.81 (d, J=15.4 Hz, 1H),
4.57 (d, J=15.4 Hz, 1H) 4.08 (bs, 2H), 3.90 (m, 1H)
3.42 (m, 1H), 6.50 (m, 6H), 2.79 (m, 1H), 2.61 (m, 1H),
2.15 (m, 3H); ESI-MS m/z 628 [M+H]+.
7-Phenoxy-3,4-dihydro-2H-quinoline-1-(4-amino-1yl-bu-
tan-1-one)-4-spiro-50-10-(1H-indol-3-ylmethyl)-30-methyl-
imidazolidine-20,40-dione (17). Prepared as 14A, (90%).
1H NMR (CDCl3) d: 8.36 (bs, 1H), 7.89 (d, J=7.8 Hz,
1H), 7.34 (m, 10H), 4.94 (m, 3H), 3,75 (m, 4H), 3.28 (m,
1H), 2.67 (m, 2H), 2.36 (m, 2H), 2.05 (bs, 2H), 1.78 (m,
3H), 1.59 (m, 3H); ESI-MS m/z 628 [M+H]+.
7-Tolyxoy-30-40-dihydro-2H-quinoline-1-(4-butan-1yl-ben-
zylcarbamic acid tert-butyl ester)-4-spiro-50-10-(1H-indol-
3-yl-methyl)-30 -methy-imidazolidine-2040 -dione (19B).
Prepared as decribed for 18A. (38%). 1H NMR
(CDCl3) d 7.68 (m, 1H), 7.46 (m, 13H), 7.04 (d, J=8.3
Hz, 1H), 6.31 (bs, 1H), 6.12 (m, 1H), 5.01 (d, J=15.6 Hz,
1H), 4.32 (m, 2H), 4.16 (d, J=15.6 Hz, 1H), 3.98 (m,
1H), 3.66 (m, 3H), 3.10 (m, 5H, 2.34 (s, 3H), 2.04 (m, 1H,
1.77 (m, 5H), 1.45 (s, 9H); ESI-MS: m/z 727 [M+H]+.
7-Phenoxy-30-40-dihydro-2H-quinoline-1-(butyl-1-yl-ben-
zylcarbamic acid tert butyl ester)-4-spiro-50-10-(1H-indol-
3-yl-methyl)-30-methy-imidazolidine-2040-dione (18A). To
a solution of 15A (0.036 g, 0.08 mmol), N-benzyl-N-(t-
butoxycarbonyl)-4-amino-1-butanal (0.033 g, 0.12
mmol) in anhydrous DCM (2 mL), and NaBH(OAc)3
were added all in once. The reaction mixture was let to
stir at room temperature for 8 h. The reaction mixture
was diluted with ethyl acetate and washed with water
and a 5% NaHCO3, dried over Na2SO4, and evapo-
rated to dryness under vacuum brine. Chromatography
on silica gel (hexanes/ethyl acetate 6:4) yielded 18A
7-Tolyxoy-30-40-dihydro-2H-quinoline-1-(4-benzylamino-
butan-1yl)-4-spiro-50-10-(1H-indol-3-yl-methyl)-30methy-
imidazolidine-2040-dione (19C). (68%). 1H NMR
(CDCl3) d: 8.02 (bs, 1H), 7.69 (m, 1H), 7.32 (m, 5H),
7.08 (m, 2H), 6.67 (d, J=8.4 Hz, 1H), 6.18 (m, 2H), 5.07
(d, J=15.6 Hz, 1H), 4.25 (d, J=15.5 Hz, 1H), 3.84 (m,
2H), 3.70 (m, 1H), 3.28 (m, 1H), 3.08 (s, 3H), 2.79 (m,
1H), 2.60 (m, 4H), 2.34 (s, 3H), 2.15 (m, 1H), 1.78 (m,
1H); ESI-MS m/z 467 [M+H]+.
1
(0.03 g, 73.2% yield based on recovered SM). H NMR
(CDCl3) 7.67 (m, 1H), 7.36 (m, 15H), 6.86 (b.s, 1H),
6.68 (d, J=8.2 Hz, 1H), 6.30 (b.s, 1H), 6.14 (m, 1H),
4.42 (b.s.,2H), 3.63 (bs, 2H) 3.22 (m, 5H) 1.45 (s, 14H)
1.33 (m, 2H); ESI-MS m/z 714 [M+H]+.
7-Tolyloxy-30 -40 -dihydro-2H-quinoline-1-(aminobutan-
1yl)-4-spiro-50-10-(1H-indol-3-yl-methyl)-30methy-imida-
zolidine-2040-dione (19). Prepared as 14A, (43%). 1H
NMR (CDCl3) d: 9.30 (bs, 1H), 7.65 (m, 1H), 7.30 (m,
1H), 7.03 (m, 5H), 6.90 (m, 3H), 6.65 (m, 1H), 6.29 (m,
1H), 6.10 (m, 2H), 5.29 (m, 1H), 4.18 (m, 1H), 3.47 (m,
1H), 3.14 (s, 3H), 2.82 (m, 2H), 2.54 (m, 3H), 2.33(s,
3H), 1.62 (m, 4H); ESI-MS m/z 538 [M+H]+.
7-Phenoxy-30-40-dihydro-2H-quinoline-1-(4-benzylamino-
butan-1yl-)-4-spiro-50-10-(1H-indol-3-yl-methyl)-30-me-
thy-imidazolidine-2040-dione (18B). Prepared as 16,
(91%). 1H NMR (CDCl3) d: 9.36 (bs, 1H), 7.66 (d,
J=7.8 Hz, 1H), 7.33 (m, 7H), 7.21 (d, J=7.8 Hz), 7.15
(m, 1H), 7.10 (m, 2H), 7.02 (d, J=7.7 Hz, 1H), 6.33 (m,
1H), 6.17 (m, 1H), 5.17 (d, J=15.4 Hz, 1H), 4.13 (d,
J=15.4 Hz, 1H), 3.81 (m, 2H), 3.78 (m, 1H), 3.28 (m,
1H), 3.05 (s, 3H), 3.00 (m, 1H), 2.79 (m, 1H), 2.67 (m,
4H), 1.84 (m, 1H), 1.57 (m, 2H); ESI-MS m/z 614
[M+H]+.
7-Hydroxy-30-40-dihydro-2H-quinoline-1-(butyl-1-yl-ben-
zylcarbamic acid tert butyl ester)-4-spiro-50-10-methyl-30
[2(ꢀ1H-indol-3-yl)-ethyl-1-carboxylic acid tert-butyl es-
ter]-imidazolidine-2040-dione (21A). Prepared as 18A,
1
(65%). H NMR (CDCl3) d: 8.14 (d, J=8.3 Hz, 1H),
7.64 (d, J=8.6 Hz, 1H), 7.44 (s, 1H), 7.32 (m, 7H), 6.98
(m, 1H), 6.47 (m, 1H), 6.08 (m, 1H), 4.43 (s, 2H), 3.83
7-Phenoxy-30-40-dihydro-2H-quinoline-1-(4-amino-butan-
1yl-)-4-spiro-50-10-(1H-indol-3-yl-methyl)-30methy-imida-