1784 Journal of Medicinal Chemistry, 2010, Vol. 53, No. 4
Lundquist et al.
Isopropyl 1,1-Dimethyl-3-[4-(2-morpholin-4-ylethoxy)benzoyl]-
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14m. 1H
NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H), 7.77-7.74 (m,
2H), 7.55 (ddd, J = 1.0, 1.0, 8.0 Hz, 1H), 7.51 (d, J = 9.0 Hz,
2H), 7.10-7.04 (m, 3H), 6.98 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H),
5.05 (quin, J = 6.2 Hz, 1H), 4.16 (t, J = 5.7 Hz, 2H), 3.97 (br s,
2H), 3.57 (t, J = 4.6 Hz, 4H), 2.70 (t, J = 5.6 Hz, 2H),
2.48-2.43 (m, 4H), 1.51 (s, 6H), 1.18 (d, J = 6.2 Hz, 6H);
HRMS: calcd for C31H37N3O5 þ Hþ, 532.2806; found (ESI,
[M þ H]þ), 532.2811; Analytical HPLC: Rt = 10.6 min (98.9%).
Isopropyl 1,1-Dimethyl-3-{4-[2-(4-methylpiperazin-1-yl)ethoxy]-
benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14n.
1H NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 7.89 (s, 1H), 7.82
(dd, J = 1.0, 8.0 Hz, 1H), 7.58 (d, J = 8.9 Hz, 2H), 7.38 (ddd, J =
1.0, 1.0, 8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.07 (ddd,
J = 1.0, 7.0, 8.0 Hz, 1H), 6.92 (d, J = 8.9 Hz, 2H), 5.14 (quin, J =
6.2 Hz, 1H), 4.15 (t, J = 5.8 Hz, 2H), 4.12 (br s, 2H), 2.83 (t, J = 5.8
Hz, 2H), 2.63 (br s, 4H), 2.48 (br s, 4H), 2.30 (s, 3H), 1.62 (s, 6H),
1.22 (d, J = 6.2 Hz, 6H); HRMS: calcd for C32H40N4O4 þ Hþ,
545.3122; found (ESI, [M þ H]þ), 545.3125; Analytical HPLC:
Rt = 10.2 min (98.5%).
Isopropyl 3-{4-[3-(Dimethylamino)propoxy]benzoyl}-1,1-di-
methyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14o.
1H NMR (400 MHz, CDCl3) δ 10.72 (s, 1H), 7.89 (s, 1H), 7.82
(dd, J = 1.0, 8.0 Hz, 1H), 7.57 (d, J = 9.0 Hz, 2H), 7.38 (ddd, J =
1.0, 1.0, 8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.07
(ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H),
5.14 (quin, J = 6.2 Hz, 1H), 4.06 (t, J = 6.4 Hz, 2H), 4.01 (br s,
2H), 2.45 (t, J = 7.2 Hz, 2H), 2.25 (s, 6H), 1.97 (quin, J = 6.8 Hz,
2H), 1.62 (s, 6H), 1.22 (d, J = 6.2 Hz, 6H); HRMS: calcd for
C30H37N3O4 þ Hþ, 504.2857; found (ESI, [M þ H]þ), 504.2857;
Analytical HPLC: Rt = 10.1 min (82.5%).
Isopropyl 1,1-Dimethyl-3-[4-(3-pyrrolidin-1-ylpropoxy)benzoyl]-
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14p. 1H
NMR (400 MHz, CDCl3) δ 10.72 (s, 1H), 7.89 (s, 1H), 7.82
(dd, J = 1.0, 8.0 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.38 (ddd,
J = 1.0, 1.0, 8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H),
7.07 (ddd, 1H), 6.91 (d, J = 9.0 Hz, 2H), 5.14 (quin, J = 6.2
Hz, 1H), 4.08 (t, J = 6.4 Hz, 2H), 4.03 (br s, 2H), 2.64 (t, J =
7.4 Hz, 2H), 2.59-2.49 (m, 4H), 2.06-2.00 (m, 2H),
1.82-1.78 (m, 4H), 1.62 (s, 6H), 1.22 (d, J = 6.2 Hz, 6H);
HRMS: calcd for C32H39N3O4 þ Hþ, 530.3013; found (ESI,
[M þ H]þ), 530.3016; Analytical HPLC: Rt = 10.3 min
(75.2%).
Isopropyl 1,1-Dimethyl-3-[4-(3-piperidin-1-ylpropoxy)benzoyl]-
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14q. 1H
NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 7.89 (s, 1H), 7.82
(dd, J = 1.0, 8.0 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.39 (ddd,
J = 1.0, 1.0, 8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H),
7.07 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 6.90 (d, J = 8.8 Hz, 2H),
5.15 (quin, J = 6.2 Hz, 1H), 4.07 (t, J = 6.2 Hz, 2H), 4.00 (br s,
2H), 2.71-2.55 (m, 6H), 2.16-2.06 (m, 2H), 1.76-1.66 (m,
4H), 1.62 (s, 6H), 1.50 (br s, 2H), 1.22 (d, J = 6.2 Hz, 6H);
HRMS: calcd for C33H41N3O4 þ Hþ, 544.3170; found (ESI,
[M þ H]þ), 544.3172; Analytical HPLC: Rt = 10.4 min
(100%).
1H), 7.38 (ddd, J = 1.0, 1.0, 8.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H),
7.20-7.14(m, 2H), 7.12-7.04 (m, 3H), 5.12 (quin, J= 6.2 Hz, 1H),
4.10 (t, J = 5.6 Hz, 2H), 4.02 (br s, 2H), 2.76 (t, J = 5.6 Hz, 2H),
2.35 (s, 6H), 1.63 (s, 6H), 1.19(d, J= 6.2 Hz, 6H); HRMS: calcd for
C29H35N3O4 þ Hþ, 490.2700; found (ESI, [M þ H]þ), 490.2691;
Analytical HPLC: Rt = 9.8 min (98.8%).
Isopropyl
1,1-Dimethyl-3-[3-(2-pyrrolidin-1-ylethoxy)benzoyl]-
1
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14t. H NMR
(400 MHz, CDCl3) δ 10.71 (s, 1H), 7.84 (s, 1H), 7.82 (dd, J = 1.0,
8.0 Hz, 1H), 7.38(ddd, J = 1.0, 1.0, 8.2 Hz, 1H), 7.31 (t, J= 7.9Hz,
1H), 7.20-7.14 (m, 2H), 7.11-7.05 (m, 3H), 5.12 (quin, J =6.2Hz,
1H), 4.16 (t, J = 5.6 Hz, 2H), 4.09 (br s, 2H), 2.96 (t, J = 5.6 Hz,
2H), 2.69 (br s, 4H), 1.88-1.79 (m, 4H), 1.63 (s, 6H), 1.19 (d, J =
6.2 Hz, 6H); HRMS: calcd for C31H37N3O4 þ Hþ, 516.2857; found
(ESI, [M þ H]þ), 516.2850; Analytical HPLC: Rt = 10.0 min
(83.3%).
Isopropyl 1,1-Dimethyl-3-[3-(2-piperidin-1-ylethoxy)benzoyl]-
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14u. 1H
NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 7.84 (s, 1H), 7.82
(dd, J = 1.0, 8.0 Hz, 1H), 7.38 (ddd, J = 1.0, 1.0, 8.0 Hz, 1H),
7.31 (t, J = 8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.14
(dd, J = 1.4, 2.5 Hz, 1H), 7.11-7.04 (m, 3H), 5.12 (quin, J = 6.2
Hz, 1H), 4.13 (t, J = 5.9 Hz, 2H), 4.08 (br s, 2H), 2.79 (t, J = 5.9
Hz, 2H), 2.52 (br s, 4H), 1.63 (s, 6H), 1.62-1.56 (m, 4H),
1.48-1.40 (m, 2H), 1.19 (d, J = 6.2 Hz, 6H); HRMS:
calcd for C32H39N3O4 þ Hþ, 530.3013; found (ESI, [M þ H]þ),
530.3006; Analytical HPLC: Rt = 10.1 min (95.6%).
Isopropyl 1,1-Dimethyl-3-[3-(2-morpholin-4-ylethoxy)benzoyl]-
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14v. H NMR
1
(400 MHz, CDCl3) δ 10.70 (s, 1H), 7.85-7.80 (m, 2H), 7.38 (ddd,
J = 1.0, 1.0, 8.0 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.21-7.13 (m,
2H), 7.13-7.03 (m, 3H), 5.12 (quin, J = 6.2 Hz, 1H), 4.13 (t, J =
5.4 Hz, 2H), 4.04 (br s, 2H), 3.72 (t, J = 4.3 Hz, 4H), 2.81 (t, J =
4.3 Hz, 2H), 2.57 (br s, 4H), 1.63 (s, 6H), 1.19 (d, J = 6.2 Hz,
6H); HRMS: calcd for C31H37N3O5 þ Hþ, 532.2806; found (ESI,
[M þ H]þ), 532.2799; Analytical HPLC: Rt = 10.5 min (100%).
Isopropyl 1,1-Dimethyl-3-{3-[2-(4-methylpiperazin-1-yl)ethoxy]-
benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14w.
1H NMR (400 MHz, CDCl3) δ 10.70 (s, 1H), 7.84 (s, 1H), 7.82
(d, J = 8.2 Hz, 1H), 7.38 (dd, J = 1.0, 8.2 Hz, 1H), 7.31 (t, J =
7.9 Hz, 1H), 7.21-7.13 (m, 2H), 7.13-7.04 (m, 3H), 5.12 (quin,
J= 6.2 Hz, 1H), 4.11 (t, J= 5.6 Hz, 2H), 4.03 (br s, 2H), 2.82 (t, J=
5.6Hz, 2H), 2.65(brs, 4H), 2.52(brs, 4H), 2.32(s, 3H), 1.63(s, 6H),
1.19 (d, J = 6.2 Hz, 6H); HRMS: calcd for C32H40N4O4 þ Hþ,
545.3122; found (ESI, [M þ H]þ), 545.3116; Analytical HPLC:
Rt = 10.1 min (97.3%).
Isopropyl 3-{3-[3-(Dimethylamino)propoxy]benzoyl}-1,1-di-
methyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14x.
1H NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 7.85 (s, 1H), 7.82 (d,
J = 8.2 Hz, 1H), 7.38 (ddd, J = 1.0, 1.0, 8.0 Hz, 1H), 7.31 (t, J =
8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.14 (dd, J =
1.6, 2.5 Hz, 1H), 7.10-7.07 (m, 2H), 7.07-7.03 (m, 1H), 5.12
(quin, J = 6.2 Hz, 1H), 4.08 (br s, 2H), 4.03 (t, J = 6.4 Hz, 2H),
2.48 (t, J = 7.3 Hz, 2H), 2.27 (s, 6H), 1.98 (dd, J = 6.4, 7.3 Hz,
2H), 1.63 (s, 6H), 1.19 (d, J = 6.2 Hz, 6H); HRMS: calcd for
C30H37N3O4 þ Hþ, 504.2857; found (ESI, [M þ H]þ), 504.2850;
Analytical HPLC: Rt = 10.0 min (98.5%).
Isopropyl 1,1-Dimethyl-3-{4-[3-(4-methylpiperazin-1-yl)pro-
poxy]benzoyl}-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxy-
Isopropyl 1,1-Dimethyl-3-[3-(3-pyrrolidin-1-ylpropoxy)benzoyl]-
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14y. H NMR
1
1
late 14r. H NMR (400 MHz, CDCl3) δ 10.71 (s, 1H), 7.89 (s,
1H), 7.82 (dd, J = 1.0, 8.0 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.38
(ddd, J = 1.0, 1.0, 8.0 Hz, 1H), 7.17 (ddd, J = 1.0, 7.0, 8.0 Hz,
1H), 7.07 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 6.91 (d, J = 8.8 Hz,
2H), 5.14 (quin, J = 6.2 Hz, 1H), 4.06 (t, J = 6.4 Hz, 2H), 4.00
(br s, 2H), 2.57-2.49 (m, 2H), 2.45 (br s, 8H), 2.29 (s, 3H),
1.94-2.03 (m, 2H), 1.62 (s, 6H), 1.22 (d, J = 6.2 Hz, 6H);
HRMS: calcd for C33H42N4O4 þ Hþ, 559.3279; found (ESI,
[M þ H]þ), 559.3280; Analytical HPLC: Rt = 10.4 min (91.4%).
Isopropyl 3-{3-[2-(Dimethylamino)ethoxy]benzoyl}-1,1-dimethyl-
(400 MHz, CDCl3) δ 10.71 (s, 1H), 7.85 (s, 1H), 7.82 (dd, J = 1.0,
8.0 Hz, 1H), 7.38(ddd, J = 1.0, 1.0, 8.0 Hz, 1H), 7.31 (t, J= 7.8Hz,
1H), 7.17 (ddd, J = 1.0, 8.0, 8.0 Hz, 1H), 7.15-7.11 (m, 1H),
7.11-7.03 (m, 3H), 5.12 (quin, J = 6.2 Hz, 1H), 4.10 (br s, 2H), 4.05
(t, J = 6.3 Hz, 2H), 2.67-2.76 (m, 2H), 2.63 (br s, 4H), 2.12-2.02
(m, 2H), 1.89-1.80 (m, 4H), 1.63 (s, 6H), 1.19 (d, J = 6.2 Hz,
6H); HRMS: calcd for C32H39N3O4 þ Hþ, 530.3013; found (ESI,
[M þ H]þ), 530.3006; Analytical HPLC: Rt = 10.2 min (88.3%).
Isopropyl 1,1-Dimethyl-3-[3-(3-piperidin-1-ylpropoxy)benzoyl]-
1
1
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14s. H NMR
(400 MHz, CDCl3) δ 10.71 (s, 1H), 7.84 (s, 1H), 7.82 (d, J = 8.0 Hz,
1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate 14z. H NMR
(400 MHz, CDCl3) δ 10.71 (s, 1H), 7.86 (s, 1H), 7.82 (dd, J = 1.0,