2562 J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 13
D’Alessio et al.
2-(5-Meth oxy-1H-in d ol-2-yl)-4-m eth oxy-5-[(5-u n d ecyl-
2H-p yr r ol-2-ylid en e)m eth yl]-2,2′-bi-1H-p yr r ole, h yd r o-
ch lor id e (9): 44%; H NMR (200 MHz, CDCl3) 0.85 (m, 3H),
1.2-1.5 (m, 16H), 1.8 (m, 2H), 3.0 (m, 2H), 3.9 (s, 3H), 4.05 (s,
3H), 6.3 (m, 2H), 6.9-7.05 (m, 4H), 7.1 (m, 1H), 7.5 (m, 1H),
12.3 (bs, 1H), 13.05-13.15 (m, 2H); MS m/z 474 [M + H]+.
Anal. (C30H39N3O2‚HCl) C, H, N.
4-Meth oxy-5-[(5-tr id ecyl-2H-p yr r ol-2-ylid en e)m eth yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (21): 60%; 1H NMR (200
MHz, CDCl3) 0.85 (t, J ) 7.7 Hz, 3H), 1.1-1.5 (m, 20H), 1.7
(m, 2H), 2.9 (t, J ) 7.7 Hz, 2H), 4.0 (s, 3H), 6.05 (m, 1H), 6.2
(m, 1H), 6.35 (m, 1H), 6.8 (m, 1H), 6.9 (m, 1H), 7.0 (s, 1H),
7.25 (m, 1H), 12.55-12.7 (bs, 2H), 12.9 (bs, 1H); MS m/z 422
[M + H]+. Anal. (C27H39N3O‚HCl) C, H, N.
1
2-(5-Ch lor o-1H-in d ol-2-yl)-4-m eth oxy-5-[(5-u n decyl-2H-
p yr r ol-2-ylid en e)m eth yl]-2,2′-bi-1H-p yr r ole, h yd r och lo-
r id e (10): 35%; 1H NMR (200 MHz, CDCl3) 0.85 (m, 3H), 1.2-
1.5 (m, 16H), 1.8 (m, 2H), 3.0 (m, 2H), 4.05 (s, 3H), 6.3 (m,
2H), 6.9-7.1 (m, 3H), 7.25 (m, 1H), 7.5 (m, 2H), 12.5,(bs, 1H),
13.1 (bs, 1H), 13.2 (bs, 1H); MS m/z 478 [M + H]+. Anal.
(C29H36ClN3O‚HCl) C, H, N.
4-Meth oxy-5-[(5-p en ta d ecyl-2H-p yr r ol-2-ylid en e)m eth -
yl]-2,2′-bi-1H-p yr r ole, h yd r och lor id e (22): 52%; H NMR
1
(200 MHz, CDCl3) 0.9 (m, 3H), 1.2-1.5 (m, 24H), 1.8 (m, 2H),
2.90 (t, J ) 7.5 Hz, 2H), 4.05 (s, 3H), 6.1 (s, 1H), 6.2 (m, 1H),
6.35 (m, 1H), 6.85 (m, 1H), 6.95 (m, 1H), 7.0 (s, 1H), 7.3 (m,
1H), 12.7 (bs, 2H), 12.9 (bs, 1H); MS m/z 450 [M + H]+. Anal.
(C29H43N3O‚HCl) C, H, N.
4-Meth oxy-5-[(5-ph en eth yl-2H-pyr r ol-2-yliden e)m eth yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (23): 62%; 1H NMR (200
MHz, CDCl3) 3.05-3.3 (m, 4H), 4.0 (s, 3H), 6.15 (m, 2H), 6.4
(m, 1H), 6.8 (m, 1H), 6.95 (m, 1H), 7.05 (s, 1H), 7.1-7.4 (m,
6H), 12.65-12.95 (3 bs, 3H); MS m/z 344 [M + H]+. Anal.
(C22H21N3O‚HCl) C, H, N.
4-Meth oxy-5-[(4,5,6,7-tetr a h yd r o-2H-in d ol-2-ylid en e)-
m eth yl]-2,2′-bi-1H-p yr r ole, h yd r och lor id e (24): 80%; 1H
NMR (200 MHz, CDCl3) 1.4-1.9 (m, 4H), 2.5 (t, J ) 6.2 Hz,
2H), 3.0 (t, J ) 6.1 Hz, 2H), 4.0 (s, 3H), 6.1 (s, 1H), 6.35 (m,
1H), 6.6 (s, 1H), 6.9 (m, 1H), 7.0 (s, 1H), 7.25 (m, 1H), 12.6 (m,
3H); MS m/z 294 [M + H]+. Anal. (C18H19N3O‚HCl) C calcd
65.54, found 64.98; H; N calcd 12.74, found 12.03.
4-Meth oxy-5-[[5-(6-flu or o-h ex-1-yl)-2H-pyr r ol-2-yliden e]-
m eth yl]-2,2′-bi-1H-p yr r ole, h yd r och lor id e (25): 35%; 1H
NMR (200 MHz, CDCl3) 0.85 (m, 2H), 1.3-1.7 (m, 6H), 2.75
(m, 2H), 4.05 (s, 3H), 4.36 (t, J ) 6.1 Hz, 1H), 4.48 (t, J ) 6.1
Hz, 1H), 6.4 (m, 1H), 6.45 (m, 1H), 6.8 (s, 1H), 7.25 (s, 1H),
7.5 (m, 3H), 12.4-12.6 (m, 3H); MS m/z 342 [M + H]+. Anal.
(C20H24FN3O‚HCl) C, H, N.
4-Meth oxy-5-[[5-(7-cyan o-h ept-1-yl)-2H-pyr r ol-2-yliden e]-
m eth yl]-2,2′-bi-1H-p yr r ole, h yd r och lor id e (26): 48%; 1H
NMR (200 MHz, CDCl3) 0.9 (m, 3H), 1.3-1.9 (m, 10H), 2.35
(t, J ) 7.0 Hz, 2H), 2.90 (t, J ) 7.5 Hz, 2H), 3.45 (s, 3H), 4.05
(s, 3H), 6.1 (m, 1H), 6.2 (m, 1H), 6.4 (m, 1H), 6.85 (m,1H), 6.95
(m, 1H), 7.0 (s, 1H), 7.3 (m, 1H), 12.7 (2 bs, 2H), 12.9 (bs, 1H);
MS m/z 363 [M + H]+. Anal. (C22H26N4O‚HCl) C, H, N.
4-Met h oxy-5-[[5-(6-h yd r oxy-h ex-1-yl)-2H-p yr r ol-2-yli-
d en e]m eth yl]-2,2′-bi-1H-p yr r ole, h yd r och lor id e (27): 35%;
1H NMR (200 MHz, CDCl3) 1.2-1.5 (m, 6H), 1.7 (m, 2H), 2.8
(t, J ) 7.7 Hz, 2H), 3.3 (m, 2H), 4.05 (s, 3H), 4.3 (m, 1H), 6.4
(m, 2H), 6.8 (m, 1H), 7.25 (s, 1H), 7.5 (m, 3H), 12.4 (bs, 1H),
12.8 (m, 2H); MS m/z 340 [M + H]+. Anal. (C20H25N3O2‚HCl)
C calcd 64.23, found 64.86; H; N.
4-E t h oxy-5-[(5-u n d ecyl-2H -p yr r ol-2-ylid en e)m et h yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (12): 35%; 1H NMR (200
MHz, CDCl3) 0.85 (m, 3H), 1.1-1.9 (m, 21H), 2.95 (m, 2H),
4.25 (q, J ) 7.0 Hz, 2H), 6.05 (d, J ) 1.8 Hz, 1H), 6.21 (dd,
J ) 1.5 Hz, J ) 4.0 Hz, 1H), 6.37 (m, 1H), 6.86 (dd, J ) 4.0
Hz, J ) 2.4 Hz, 1H), 6.94 (m, 1H), 7.03 (s, 1H), 7.25 (m, 1H),
12.6-13.0 (2 bs, 3H); MS m/z 408 [M + H]+. Anal. (C26H37N3O‚
HCl) C, H, N.
4-P r op oxy-5-[(5-u n d ecyl-2H-p yr r ol-2-ylid en e)m eth yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (13): 40%: 1H NMR (200
MHz, CDCl3) 0.85 (t, J ) 6.6 Hz, 3H), 1.07 (t, J ) 7.5 Hz, 3H),
1.1-1.5 (m, 16H), 1.76 (m, 2H), 1.90 (m, 2H), 2.93 (t, J ) 7.5
Hz, 2H), 4.12 (t, J ) 6.5 Hz, 2H), 6.04 (d, J ) 1.6 Hz, 1H),
6.19 (dd, J ) 4.0, 1.2 Hz, 1H), 6.35 (m, 1H), 6.84 (dd, J ) 4.0,
1.9 Hz, 1H), 6.92 (m, 1H), 7.0 (s, 1H), 7.23 (m, 1H), 12.5-13.0
(bs, 3H); MS m/z 422 [M + H]+. Anal. (C27H39N3O‚HCl) C, H,
N.
4-Isop r op oxy-5-[(5-u n d ecyl-2H-p yr r ol-2-ylid en e)m eth -
1
yl]-2,2′-bi-1H-p yr r ole, h yd r och lor id e (14): 39%; H NMR
(200 MHz, CDCl3) 0.9 (m, 3H), 1.2-1.3 (m, 16H), 1.45 (2s, 6H),
1.7 (m, 2H), 2.9 (m, 2H), 4.6 (m, 1H), 6.0 (m, 1H), 6.2 (m, 1H),
6.35 (m, 1H), 6.85 (m,1H), 6.9 (m, 1H), 7.0 (s, 1H), 7.25 (m,
1H), 7.45 (m, 5H), 12.7 (bs, 2H), 12.8 (bs, 1H); MS m/z 422
[M + H]+. Anal. (C27H39N3O‚HCl) C, H, N.
4-Bu t oxy-5-[(5-u n d ecyl-2H -p yr r ol-2-ylid en e)m et h yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (15): 54%; 1H NMR (200
MHz, CDCl3) 0.85 (t, J ) 6.8 Hz, 3H), 1.0 (t, J ) 7.3 Hz, 3H),
1.1-1.6 (m, 18H), 1.6-1.9 (m, 4H), 2.9 (t, J ) 7.3 Hz, 2H),
4.15 (t, J ) 6.7 Hz, 2H), 6.05 (m, 1H), 6.2 (m, 1H), 6.35 (m,
1H), 6.85 (m, 1H), 6.95 (m, 1H), 7.0 (s, 1H), 7.25 (m, 1H), 12.7
(2 bs, 2H), 12.85 (bs, 1H); MS m/z 436 [M + H]+. Anal.
(C28H41N3O‚HCl) C, H, N.
4-Ben zyloxy-5-[(5-u n decyl-2H-pyr r ol-2-yliden e)m eth yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (16): 64%; 1H NMR (200
MHz, CDCl3) 0.9 (m, 3H), 1.2-1.5 (m, 16H), 1.75 (m, 2H), 2.95
(m, 2H), 5.2 (s, 2H), 6.15 (m, 1H), 6.2 (m, 1H), 6.35 (m, 1H),
6.85 (m, 1H), 6.95 (m, 1H), 7.05 (s, 1H), 7.25 (m, 1H), 7.45 (m,
5H), 12.6-12.8 (2 bs, 2H), 12.95 (bs, 1H); MS m/z 470 [M +
H]+. Anal. (C31H39N3O‚HCl) C, H, N.
4-Met h oxy-5-[(5-p en t yl-2H -p yr r ol-2-ylid en e)m et h yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (18): 35%; 1H NMR (200
MHz, CDCl3) 0.9 (m, 3H), 1.3-1.5 (m, 4H), 1.8 (m, 2H), 2.95
(t, J ) 7.5 Hz, 2H), 4.0 (s, 3H), 6.1 (s, 1H), 6.1 (m, 1H), 6.2 (m,
1H), 6.35 (m, 1H), 6.85 (m, 1H), 6.9 (m, 1H), 7.0 (s, 1H), 7.25
(m, 1H), 12.7 (bs, 2H), 13.0 (bs, 1H); MS m/z 310 [M + H]+.
Anal. (C19H23N3O‚HCl) C, H, N.
4-Met h oxy-5-[(5-(5-ca r b oxy-p en t -1-yl)-2H -p yr r ol-2-yl-
iden e)m eth yl]-2,2′-bi-1H-pyr r ole, h ydr och lor ide (28): 36%;
1H NMR (200 MHz, CDCl3) 1.2-2.1 (m, 6H), 2.35 (t, J ) 7.5
Hz, 2H), 2.95 (t, J ) 7.5 Hz, 2H), 4.05 (s, 3H), 6.1 (s, 1H), 6.2
(m, 1H), 6.35 (m, 1H), 6.85 (m, 1H), 6.9 (m, 1H), 7.0 (s, 1H),
7.25 (s, 1H), 12.5-12.9 (m, 3H); MS m/z 354 [M + H]+. Anal.
(C20H23N3O3‚HCl) C calcd 61.61, found 60.54; H; N calcd 10.77,
found 9.01.
4-Met h oxy-5-[(5-(5-ca r b oxy-p en t -1-yl)-2H -p yr r ol-2-yl-
id en e)m eth yl]-2,2′-bi-1H-p yr r ole, m eth yl ester , h yd r o-
1
ch lor id e (29): 32%; H NMR (200 MHz, CDCl3) 1.2-1.9 (m,
6H), 2.35 (t, J ) 7.5 Hz, 2H), 2.95 (t, J ) 7.5 Hz, 2H), 3.65 (s,
3H), 4.05 (s, 3H), 6.1 (m, 1H), 6.2 (m, 1H), 6.4 (m, 1H), 6.85
(m, 1H), 6.95 (m, 1H), 7.05 (s, 1H), 7.25 (m, 1H), 12.6-12.8
(m, 3H); MS m/z 368 [M + H]+. Anal. (C21H25N3O3‚HCl) C, H,
N.
4-Met h oxy-5-[(5-h ep t yl-2H -p yr r ol-2-ylid en e)m et h yl]-
2,2′-bi-1H-p yr r ole, h yd r och lor id e (19): 46%; 1H NMR (200
MHz, CDCl3) 0.9 (m, 3H), 1.25-1.45 (m, 8H), 1.8 (m, 2H), 2.95
(m, 2H), 4.05 (s, 3H), 6.1 (m, 1H), 6.25 (m, 1H), 6.4 (m, 1H),
6.85 (m, 1H), 6.95 (m, 1H), 7.05 (s, 1H), 7.25 (m, 1H), 12.65-
12.75 (2 bs, 2H), 12.95 (bs, 1H); MS m/z 338 [M + H]+. Anal.
(C21H27N3O‚HCl) C, H, N.
4-Meth oxy-5-[[5-(5-m or p h olin eca r boa m id e-p en t-1-yl)-
2H-p yr r ol-2-ylid en e]m eth yl]-2,2′-bi-1H-p yr r ole, h yd r o-
1
ch lor id e (30): 38%; H NMR (200 MHz, CDCl3) 1.1-1.8 (m,
6H), 2.3 (t, J ) 7.3 Hz, 2H), 2.7 (t, J ) 7.4 Hz, 2H), 3.2-3.6
(m, 8H), 4.0 (s, 3H), 6.4 (m, 2H), 6.8 (s, 1H), 7.2 (s, 1H), 7.5
(m, 3H), 12.2-12.8 (2 bs, 3H); MS m/z 423 [M + H]+. Anal.
(C24H30N4O3‚HCl) C, H, N.
4-Met h oxy-5-[[5-(10-ca r boxy-d ec-1-yl)-2H-p yr r ol-2-yl-
iden e]m eth yl]-2,2′-bi-1H-pyr r ole, h ydr och lor ide (31): 30%;
1H NMR (200 MHz, CDCl3) 1.2-1.5 (m, 12H), 1.5-1.9 (2m,
4-Meth oxy-5-[(5-decyl-2H-pyr r ol-2-yliden e)m eth yl]-2,2′-
bi-1H-p yr r ole, h yd r och lor id e (20): 48%; 1H NMR (200
MHz, CDCl3) 0.9 (t, J ) 7.7 Hz, 3H), 1.2-1.5 (m, 14H), 1.75
(m, 2H), 2.95 (t, J ) 7.7 Hz, 2H), 4.05 (s, 3H), 6.1 (s, 1H), 6.25
(m, 1H), 6.35 (m, 1H), 6.85 (m, 1H), 6.95 (m, 1H), 7.05 (s, 1H),
7.25 (m, 1H), 12.54-12.62 (2 bs, 2H), 12.93 (bs, 1H); MS m/z
380 [M + H]+. Anal. (C24H33 N3O‚HCl) C, H, N.