L. D. Jennings et al. / Bioorg. Med. Chem. 12 (2004) 5115–5131
5125
bonate resin (0.661g, 3equiv) (Argonaut Technologies,
Foster City, CA) was added and the reaction was shaken
for a further 5h. Scavenging of excess amine was con-
firmed by TLC. The reactions were filtered and concen-
trated and the crude products were redissolved in either
DMSO or MeOH and purified by RP-HPLC.
J = 5.4Hz, 2H), 2.63–2.73 (m, 1H), 2.90–2.98 (m, 1H),
3.10–3.15 (m, 1H), 3.25–3.30 (m, 1H), 3.31 (t,
J = 5.4Hz, 1H), 4.13 (br s, 1H), 4.56 (t, J = 5.4Hz,
2H), 4.60–4.70 (m, 1H), 6.56 (d, J = 3.2Hz, 1H), 7.14
(t, J = 6.4Hz, 1H), 7.21–7.29 (m, 2H), 7.35–7.50 (m,
4H), 7.62 (d, J = 7.6Hz, 1H). Anal. Calcd for
C26H31ClN3O1+
:
436.21502.
Found
436.21363
5.7.1. 3-[2-(3-Chloro-phenyl)-indol-1-yl]-N-(5-methyl-fu-
ran-2-ylmethyl)-propionamide (6.a.1). (21%); 1H NMR
(CDCl3, 400MHz) d 2.22 (s, 3H), 2.45 (t, J = 7.2Hz,
2H), 4.21 (d, J = 5.6Hz, 2H), 4.54 (t, J = 7.2Hz, 2H),
5.65 (br s, 1H), 5.85 (d, J = 2Hz, 1H), 5.99 (d,
J = 2Hz, 1H), 6.53 (s, 1H), 7.10–7.19 (m, 1H), 7.20–
7.30 (m, 1H), 7.31–7.51 (m, 5H), 7.59–7.64 (m, 1H).
Anal. Calcd for C23H22ClN2O21+: 393.13644. Found
393.13579 ([M+H]1+, D = ꢀ0.65mmu, ESI-FTMS).
([M+H]1+, D = ꢀ1.39mmu, ESI-FTMS).
5.7.7. N-(2-Acetylamino-ethyl)-3-(2-phenyl-indol-1-yl)-
propionamide (6.b.12). (17%); 1H NMR (CDCl3,
400MHz) d 1.86 (s, 3H), 2.39 (t, J = 6.8Hz, 2H), 3.02–
3.08 (m, 2H), 3.10–3.16 (m, 2H), 3.88 (s, 3H), 4.53 (t,
J = 6.8Hz, 2H), 5.48 (br s, 1H), 5.7 (br s, 1H), 6.50 (s,
1H), 7.01 (d, J = 8.8Hz, 2H), 7.13 (t, J = 5.4Hz, 1H),
7.22 (t, J = 5.4Hz, 1H), 7.42 (d, J = 8.8Hz, 2H), 7.46
(d, J = 7.6Hz, 1H), 7.60 (d, J = 7.6Hz, 1H). Anal.
Calcd for C22H26N3O31+: 380.19687. Found 380.19634
([M+H]1+,D = ꢀ0.53mmu, ESI-FTMS).
5.7.2. 3-[2-(3-Chloro-phenyl)-indol-1-yl]-N-[2-(1-methyl-
pyrrolidin-2-yl)-ethyl]-propionamide (6.a.6). (24%); 1H
NMR (CDCl3, 400MHz) d 1.40–1.50 (m, 2H), 1.53–
1.70 (m, 3H), 1.78–1.88 (m, 1H), 2.07–2.15 (m, 1H),
2.19 (s, 3H), 2.42 (t, J = 7.6Hz, 2H), 2.95–3.10 (m,
2H), 3.25–3.35 (m, 1H), 4.51 (t, J = 7.6Hz, 2H), 6.88
(br s, 1H), 7.13 (t, J = 7.4Hz, 1H), 7.25 (t, J = 7.4Hz,
1H), 7.35–7.50 (m, 5H), 7.61 (d, J = 8.4Hz, 1H). Anal.
5.7.8. 2-[2-(3-Chloro-phenyl)-indol-1-yl]-1-(2-pyrrolidin-
1-ylmethyl-pyrrolidin-1-yl)-ethanone (8.a.19). (24%), A
mixture of cis and trans isomers inseparable by chroma-
1
tography; H NMR (CDCl3, 400MHz) d 1.6–1.8 (m,
6H), 1.85–2.10 (m, 6H), 2.40–2.55 (m, 2H), 2.55–2.70
(m, 2H), 3.28–3.43 (m, 1H), 3.45–3.55 (m, 0.5H), 3.63–
3.70 (m, 0.5H), 3.95 (q, J = 6Hz, 0.5H), 4.29–4.37 (m,
0.5H), 4.74 (s, 1H), 4.78 (d, J = 18Hz, 0.5H), 5.2 (d,
J = 18Hz, 0.5H), 6.6 (d, J = 5.6Hz, 1H), 7.10–7.16 (m,
1H), 7.19–7.23 (m, 2H), 7.33–7.47 (m, 3H), 7.5 (d,
J = 13.2Hz, 1H), 7.63 (d, J = 7.6Hz, 1H). Anal. Calcd
Calcd for C24H29ClN3O1+
:
410.19937. Found
410.20007 ([M+H]1+, D = 0.7mmu, ESI-FTMS).
5.7.3. 3-[2-(3-Chloro-phenyl)-indol-1-yl]-N-(2-pyrrolidin-
1-yl-ethyl)-propionamide (6.a.7). (23%); 1H NMR
(CDCl3, 400MHz) d 1.72–1.78 (m, 4H), 2.35–2.50 (m,
4H), 2.55–2.75 (m, 4H), 3.19 (q, J = 5.6Hz, 2H), 4.53
(t, J = 6Hz, 2H), 6.44–6.50 (br s, 1H), 6.53 (s, 1H),
7.13 (t, J = 7.4Hz, 1H), 7.24 (t, J = 7.4Hz, 1H), 7.35–
7.42 (m, 3H), 7.45–7.50 (m, 2H), 7.60 (d, J = 8Hz, 1H).
Anal. Calcd for C23H27ClN3O1+: 396.18372. Found
396.18455 ([M+H]1+, D = 0.83mmu, ESI-FTMS).
for C25H29ClN3O1+
:
422.19937. Found 422.1982
([M+H]1+, D = ꢀ1.17mmu, ESI-FTMS).
5.7.9. 2-[2-(3-Chloro-phenyl)-indol-1-yl]-1-[4-(2-hydroxy-
ethyl)-piperidin-1-yl]-ethanone (8.a.22). (20%); H NMR
1
(CDCl3, 400MHz) d 1.94–1.06 (m, 1H), 1.10–1.21 (m,
1H), 1.50 (q, J = 6.4Hz, 2H), 1.55–1.80 (m, 5H), 2.59–
2.64 (m, 1H), 3.03 (t, J = 12Hz, 1H), 3.65 (t,
J = 6.4Hz, 2H), 4.59 (d, J = 13.2Hz, 1H), 4.83 (d,
J = 2Hz, 2H), 6.62 (s, 1H), 7.10–7.16 (m, 1H), 7.21–
7.23 (m, 2H), 7.36–7.40 (m, 3H), 7.45 (d, J = 1.6Hz,
5.7.4. 3-[2-(3-Chloro-phenyl)-indol-1-yl]-N-naphthalen-
1-ylmethyl-propionamide (6.a.13). (28%); 1H NMR
(CDCl3, 400MHz) d 2.44 (t, J = 7.2Hz, 2H), 4.57 (t,
J = 7.6Hz, 2H), 4.69 (d, J = 5.2Hz, 2H), 5.63–5.71 (br
s, 1H), 6.52 (s, 1H), 7.14 (t, J = 7.4Hz, 1H), 7.22–7.29
(m, 2H), 7.32–7.49 (m, 4H), 7.43–7.40 (m, 4H), 7.60 (d,
J = 8Hz, 1H), 7.77–7.82 (m, 2H), 7.82–7.87 (m, 1H).
Anal. Calcd for C28H24ClN2O1+: 439.15717. Found
439.15677 ([M+H]1+, D = ꢀ0.66mmu, ESI-FTMS).
1H), 7.63 (d, J = 7.6Hz, 1H). Anal. Calcd for
C23H26ClN2O2
1+
:
397.16774.
Found
397.16743
([M+H]1+, D = ꢀ0.31mmu, ESI-FTMS).
5.7.10. 1-{2-[2-(3-Chloro-phenyl)-indol-1-yl]-acetyl}-pip-
eridine-4-carboxylic acid ethyl ester (8.a.23). (25%); H
1
5.7.5.
3-[2-(3-Chloro-phenyl)-indol-1-yl]-1-(3-hydroxy-
NMR (CDCl3, 400MHz) d 1.27 (t, J = 7.2Hz, 3H),
1.50–1.70 (m, 2H), 1.83–2.0 (m, 2H), 2.50–2.60 (m,
1H), 2.90–3.0 (m, 1H), 3.10–3.20 (m, 1H), 3.70 (d,
J = 13.6Hz, 1H), 4.17 (q, J = 7.2Hz, 2H), 4.36 (d,
J = 13.6Hz, 1H), 4.83 (s, 2H), 6.62 (s, 1H), 7.14
(t, J = 6.8Hz, 1H), 7.19–7.23 (m, 2H), 7.37 (s, 3H),
1
pyrrolidin-1-yl)-propan-1-one (6.a.16). (12%); H NMR
(CDCl3, 400MHz) d 1.67–1.90 (m, 2H), 2.43–2.53 (m,
2H), 3.0–3.11 (m, 1H), 3.15–3.23 (m, 1H), 3.35–3.47
(m, 2H), 3.48–3.55 (m, 1H), 4.28–4.37 (m, 1H), 4.55–
4.62 (m, 2H), 6.56 (s, 1H), 7.10–7.17 (m, 1H), 7.23–
7.29 (m, 2H), 7.35–7.48 (m, 3H), 7.49 (s, 1H), 7.62 (d,
J = 7.6Hz, 1H). Anal. Calcd for C21H22ClN2O2
7.45 (s, 1H), 7.63 (d, J = 8Hz, 1H). Anal. Calcd for
C24H26ClN2O3
1+
1+
:
:
425.16265.
Found
425.16157
369.13644. Found 369.13603 ([M+H]1+
,
D =
([M+H]1+, D = ꢀ1.08mmu, ESI-FTMS).
ꢀ0.41mmu, ESI-FTMS).
5.8. N-Phenyl-N0-(1-pyridin-3-yl-ethylidene)-hydrazine
5.7.6. 3-[2-(3-Chloro-phenyl)-indol-1-yl]-1-(2-pyrrolidin-
1-ylmethyl-pyrrolidin-1-yl)-propan-1-one (6.a.19). (22%);
1H NMR (CDCl3, 400MHz) d 1.60–2.05 (m, 8H),
2.18–2.26 (m, 1H), 2.18–2.23 (m, 1H), 2.47 (t,
3-Acetylpyridine (31.1mL, 277.1mmol) was added to a
solution of phenyl hydrazine (27.3mL, 277.4mmol) in
ethanol (45mL). The reaction mixture was refluxed with