6842
K. W. Woods et al. / Bioorg. Med. Chem. 14 (2006) 6832–6846
scribed for 33) followed by deprotection of the Boc
group with TFA (as described for 59) yielded 3. 1H
NMR (300 MHz, DMSO-d6) d ppm 11.02 (br s, 1H),
9.52 (s, 1H), 8.76 (d, J = 3 Hz, 1H), 8.62 (d, J = 8 Hz,
1H), 8.44–8.46 (m, 2H), 8.38 (d, J = 9 Hz, 1H), 8.11–
8.20 (m, 3H), 8.04–8.08 (m, 1H), 7.83–7.86 (m, 1H),
7.62 (d, J = 9 Hz, 1H), 7.37–7.40 (m, 1H), 7.31 (d,
J = 3 Hz, 1H), 7.08–7.12 (m, 1H), 6.99–7.03 (m, 1H),
4.37–4.41 (m, 1H), 4.18–4.23 (m, 1H), 3.86–3.91 (m,
1H), 3.16–3.20 (m, 2H). MS (ESI): m/z (M+H)+ 395.
Anal. Calcd for C25H22N4OÆ2TFAÆH2O: C, 49.35; H,
3.61; N, 7.43; F, 22.67. Found: C, 49.04; H, 3.55; N,
7.42; F, 22.28.
deprotection of the Boc group with TFA (as described
for 59) yielded 41. H NMR (300 MHz, DMSO-d6) d
1
ppm 8.77 (s, 1H), 8.55 (d, J = 8.6 Hz, 1H), 8.45 (d,
J = 2.5 Hz, 1H), 8.20 (d, J = 1.5 Hz, 1H), 8.05 (dd,
J = 8.6, 1.8 Hz, 1H), 7.83 (dd, J = 1.8, 2.5 Hz, 1H),
7.61 (m, 2H), 7.38 (d, J = 7.1 Hz, 1H), 7.24 (s, 1H),
7.12 (m, 1H), 7.02 (m, 1H), 4.44 (dd, J = 10.4, 3.1 Hz,
1H), 4.30 (dd, J = 10.4, 5.8 Hz, 1H), 4.01 (m, 1H),
3.32 (m, 2H). MS (DCI/NH3): m/z (M+H)+ 410.
5.2.35.
6-{5-[(S)-2-amino-3-(1H-indol-3-yl)-propoxy]-
pyridin-3-yl}-1-chloro-isoquinoline (42). Stille reaction
with 6-bromo-1-chloroisoquinoline (18) and stannyl
material 8 (as described for 33) followed by deprotection
of the Boc group with TFA (as described for 59) yielded
5.2.31. (S)-2-(1H-indol-3-yl)-1-{[(5-quinolin-6-ylpyridin-
3-yl)oxy]methyl}ethylamine (38). Stille reaction with 6-
bromoquinoline and stannyl material 8 (as described
for 33) followed by deprotection of the Boc group with
TFA (as described for 59) yielded 38. 1H NMR
(500 MHz, DMSO-d6) d ppm 11.02 (s, 1H), 8.97-9.00
(m, 1H), 8.74 (d, J = 3 Hz, 1H), 8.50–8.54 (m, 1H),
8.39–8.42 (m, 2H), 8.18–8.23 (m, 3H), 8.13–8.17 (m,
1H), 7.81–7.83 (m, 1H), 7.61–7.66 (m, 2H), 7.39 (d,
J = 8 Hz, 1H), 7.31 (d, J = 3 Hz, 1H), 7.07–7.10 (m,
1H), 6.99–7.02 (m, 1H), 4.38–4.41 (m, 1H), 4.21–4.24
(m, 1H), 3.79–3.83 (m, 1H), 3.16–3.19 (m, 2H). MS
(ESI): m/z (M+H)+ 395.
1
42. H NMR (300 MHz, DMSO-d6) d ppm 11.03 (br s,
1H), 8.75 (d, J = 1.6 Hz, 1H), 8.47 (d, J = 1.6 Hz, 1H),
8.45 (d, J = 5.6 Hz, 1H), 7.84 (m, 1H), 7.62 (d,
J = 8.1 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.31 (d,
J = 2.2 Hz, 1H), 7.10 (m, 1H), 7.01 (m, 1H), 4.38 (dd,
J = 10.6, 3.1 Hz, 1H), 4.22 (dd, J = 10.4, 6.2 Hz, 1H),
3.88 (m, 1H), 3.18 (m, 2H). MS (ESI): m/z (M+H)+
429, 431.
5.2.36. (S)-1-(1H-Indol-3-ylmethyl)-2-(5-isoquinolin-5-yl-
pyridin-3-yloxy)-ethylamine (43). Stille reaction with 5-
bromoisoquinoline and stannyl material 8 (as described
for 33) followed by deprotection of the Boc group with
TFA (as described for 59) yielded 43. 1H NMR
(300 MHz, DMSO-d6) d ppm 11.02 (br s, 1H), 9.53 (s,
1H), 8.52 (d, J = 8 Hz, 1H), 8.49 (d, J = 4 Hz, 1H),
8.37 (d, J = 3 Hz, 1H), 8.30–8.34 (m, 1H), 8.15–8.19
(m, 2H), 7.84–7.88 (m, 2H), 7.68 (d, J = 8 Hz, 1H),
7.56–7.60 (m, 2H), 7.47 (d, J = 8 Hz, 1H), 7.28 (d,
J = 4 Hz, 1H), 7.60–7.12 (m, 1H), 6.94–6.99 (m, 1H),
4.12–4.32 (m, 2H), 3.82–3.87 (m, 1H), 3.13–3.17 (m,
2H). MS (ESI): m/z (M+H)+ 395.
5.2.32. (S)-2-[(5-cinnolin-6-ylpyridin-3-yl)oxy]-1-(1H-indol-
3-ylmethyl)ethylamine (39). Stille reaction with 6-bro-
mocinnoline (16) and stannyl material 8 (as described
for 33) followed by deprotection of the Boc group with
TFA (as described for 59) yielded 39. 1H NMR
(300 MHz, DMSO-d6) d ppm 11.04 (s, 1H), 9.43 (d,
J = 6 Hz, 1H), 8.78 (d, J = 2 Hz, 1H), 8.60 (d,
J = 8 Hz, 1H), 8.45–8.49 (m, 2H), 8.30–8.34 (m, 1H),
8.26 (d, J = 6 Hz, 1H), 8.21–8.25 (m, 2H), 7.89 (t,
J = 2 Hz, 1H), 7.63 (d, J = 8 Hz, 1H), 7.39 (d,
J = 8 Hz, 1H), 7.31 (d, J = 2 Hz, 1H), 7.08–7.12 (m,
1H), 7.01–7.04 (m, 1H), 4.38–4.42 (m, 1H), 4.22–4.26
(m, 1H), 3.83–3.88 (m, 1H), 3.17–3.20 (m, 2H). MS
(ESI): m/z (M+H)+ 396.
5.2.37.
(S)-2-{[5-(1H-indazol-5-yl)pyridin-3-yl]oxy}-1-
(1H-indol-3-ylmethyl)-ethylamine (48). Stille reaction
with 5-bromoindazole (23) and stannyl material 8 (as de-
scribed for 33) followed by deprotection of the Boc
1
group with TFA (as described for 59) yielded 48. H
5.2.33.
6-{5-[(S)-2-Amino-3-(1H-indol-3-yl)-propoxy]-
NMR (300 MHz, DMSO-d6) d ppm 13.22 (br s, 1H),
11.04 (br s, 1H), 8.62 (d, J = 2 Hz, 1H), 8.33 (d,
J = 3 Hz, 1H), 8.13–8.21 (m, 3H), 8.12 (s, 1H), 7.67–
7.72 (m, 3H), 7.64 (d, J = 8 Hz, 1H), 7.39 (d, J = 8Hz,
1H), 7.30 (d, J = 2 Hz, 1H), 7.06–7.13 (m, 1H), 6.98–
7.04 (m, 1H), 4.14–4.39 (m, 2H), 3.33–3.38 (m, 1H),
3.13–3.16 (m, 2H). MS (ESI): m/z (M+H)+ 384. Anal.
Calcd for C23H21N5OÆ2TFAÆH2O: C, 51.52; H, 4.00;
N, 11.13. Found: C, 51.80; H, 3.61; N, 11.03.
pyridin-3-yl}-2H-isoquinolin-1-one (40). Stille reaction
with 6-bromo-1-hydroxyisoquinoline (17) and stannyl
material 8 (as described for 33) followed by deprotection
of the Boc group with TFA (as described for 59) yielded
1
40. H NMR (300 MHz, DMSO-d6) d ppm 11.30 (br s,
1H), 11.04 (br s, 1H), 8.66–8.68 (m, 1H), 8.41 (d,
J = 3 Hz, 1H), 8.27 (d, J = 8 Hz, 1H), 8.17–8.20 (m,
2H), 8.02–8.03 (m, 1H), 7.76–7.81 (m, 2H), 7.62 (d,
J = 8 Hz, 1H), 7.38 (d, J = 8 Hz, 1H), 7.29–7.31 (m,
1H), 7.20–7.26 (m, 1H), 7.07–7.12 (m, 1H), 6.98–7.04
(m, 1H), 6.60 (d, J = 8 Hz, 1H), 4.14–4.39 (m, 2H),
3.33–3.38 (m, 1H), 3.13–3.16 (m, 2H). MS (ESI): m/z
(M+H)+ 411. Anal. Calcd for C25H22N4OÆ2TFA: C,
54.54; H, 3.78; N, 8.78. Found: C, 54.54; H, 4.00; N, 8.56.
5.2.38. (S)-2-([3,40]Bipyridinyl-5-yloxy)-1-(1H-indol-3-
ylmethyl)-ethylamine (44). Stille reaction with 4-bromo-
pyridine and stannyl material 8 (as described for 33) fol-
lowed by deprotection of the Boc group with TFA (as
described for 59) yielded 44. 1H NMR (300 MHz,
CD3OD) d ppm 8.85 (d, J = 6.8 Hz, 2H), 8.73 (d,
J = 1.7 Hz, 1H), 8.53 (d, J = 2.7 Hz, 1H), 8.20 (d,
J = 6.8 Hz, 2H), 7.84 (t, J = 1.7 Hz, 1H), 7.59 (d,
J = 7.8 Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.24 (s, 1H),
7.12 (t, J = 6.8 Hz, 1H), 7.01 (t, J = 8.1 Hz, 1H), 4.44
5.2.34.
1-Amino-6-{5-[(S)-2-amino-3-(1H-indol-3-yl)-
propoxy]-pyridin-3-yl}-isoquinoline (41). Stille reaction
with 1-bis-Boc-amino-6-bromoisoquinoline (20) and
stannyl material 8 (as described for 33) followed by