1744
K. Bhandari et al. / Bioorg. Med. Chem. 13 (2005) 1739–1747
5.1.5.4. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
5.1.5.8. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-[4-a,a,a-trifluorotolyl-
piperazino]propan-2-ol (14). With 1-(3-a,a,a-trifluoro-
tolyl)piperazine (6h). Yield 80%;MS (FAB) m/z: 596
romethylphenoxy)propyl)amino]-3-[4-(2-pyridyl)piperaz-
ino]propan-2-ol (10). With 1-(2-pyridyl)piperazine (6d).
Yield 71%;MS (FAB) m/z: 529 ([M+1]+, 80%); 1H
1
NMR (200 MHz, CDCl3):
d
2.28–2.31 (m, 2H,
([M+1]+, 100%); H NMR (200 MHz, CDCl3): d 1.99–
MeNCH2–CH2), 2.57 (s, 3H, NMe), 2.62–2.98 (m,
10H, NCH2), 3.57–3.62 (m, 4H, piperazinyl Hꢀs adjacent
to pyridyl ring), 4.15 (m, 1H, OH–CH), 5.35–5.39 (m,
1H, Ar–CH–O), 6.62 (m, 2H, ArH), 6.89–6.92 (d, 2H,
J = 8.1 Hz, ArH), 7.29–7.39 (m, 4H, ArH), 7.42–7.51
(m, 4H, ArH), 8.18–8.19 (m, 1H, ArH);IR (Neat):
3421, 1636, 1326, 1114, 762 cmꢀ1. Anal. Calcd for
C29H35F3N4O2Æ3HClÆ1.2H2O: C, 52.79;H, 6.13;N,
8.49. Found: C, 52.43;H, 5.77;N, 8.19.
2.10 (m, 2H, MeNCH2–CH2), 2.22–2.38 (m, 7H, NMe,
NCH2), 2.43–2.63 (m, 6H, NCH2), 3.11–3.16 (m, 4H,
piperazinyl Hꢀs adjacent to phenyl ring), 3.85 (m, 1H,
OH–CH), 5.18–5.25 (m, 1H, Ar–CH–O), 6.81–6.85 (d,
2H, J = 8.5 Hz, ArH ortho to O), 6.95–7.02 (m, 3H,
ArH ortho and para to N), 7.19–7.27 (m, 6H, ArH),
7.33–7.38 (d, 2H, J = 8.68 Hz, ArH ortho to CF3);IR
(Neat): 3413, 2932, 2832, 1613, 1452, 1324, 1250, 1163,
1119, 758 cmꢀ1. Anal. Calcd for C31H35F6N3O2Æ3H-
ClÆ1.25H2O: C, 50.36;H, 5.66;N, 5.69. Found: C,
50.02;H, 5.77;N, 5.86.
5.1.5.5. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-[4-(4-fluorophenyl)pip-
erazino]propan-2-ol (11). With 1-[(4-fluoro)phenyl]piper-
azine (6e). Yield 80%;MS (FAB) m/z: 546 ([M+1]+,
5.1.5.9. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-[4-methylpiperazino]-
propan-2-ol (15). With 2-methylpiperazine (6i). Yield
64%;MS (FAB) m/z: 465 ([M+1]+, 80%); 1H NMR
(200 MHz, CDCl3): d 1.7 (m, 2H, MeNCH2–CH2),
2.16 (m, 3H, NMe), 2.43–2.54 (m, 7H, piperazinyl
NMe, NCH2), 2.63–2.80 (m, 10H, NCH2), 3.9 (m, 1H,
OH–CH), 5.29–5.33 (m, 1H, Ar–CH–O), 6.87–6.91 (d,
2H, J = 8.54 Hz, ArH ortho to O), 7.32–7.33 (m, 5H,
ArH), 7.40–7.44 (d, 2H, J = 8.66 Hz, ArH ortho to
CF3);IR (Neat): 3411, 2965, 2718, 2365, 1619, 1328,
1248, 1116 cmꢀ1. Anal. Calcd for C25H34F3N3O2Æ3H-
ClÆ1.75H2O: C, 49.50;H, 6.68;N, 6.93. Found: C,
49.13;H, 6.92;N, 7.09.
1
100%); H NMR (200 MHz, CDCl3): d 2.02–2.24 (m,
2H, MeNCH2–CH2), 2.37–2.50 (m, 7H, NMe, NCH2),
2.58–2.77 (m, 6H, NCH2), 3.08–3.14 (m, 4H, piperazinyl
Hꢀs adjacent to phenyl ring), 3.87–3.89 (m, 1H, OH–
CH), 5.30–5.31 (m, 1H, Ar–CH–O), 6.83–6.99 (m, 6H,
ArH ortho to O, ArH containing F atom), 7.28–7.35
(m, 5H, ArH), 7.41–7.44 (d, 2H, J = 8.2 Hz, ArH ortho
to CF3);IR (Neat): 3429, 3020, 2964, 1721, 1216,
761 cmꢀ1. Anal. Calcd for C30H35F4N3O2Æ3HClÆ0.75-
H2O: C, 53.89;H, 5.91;N, 6.29. Found: C, 53.62;H,
6.11;N, 6.18.
5.1.5.6. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-[4-(3-chlorophenyl)pip-
erazino]propan-2-ol (12). With 1-[(3-chloro)phenyl]piper-
azine (6f). Yield 57%;MS (FAB) m/z: 561 (M+, 95%),
562 ([M+2]+, 35%); 1H NMR (200 MHz, CDCl3): d
2.03–2.17 (m, 2H, MeNCH2–CH2), 2.31–2.38 (m, 7H,
NMe, NCH2), 2.53–2.62 (m, 6H, NCH2), 3.14–3.19
(m, 4H, piperazinyl Hꢀs adjacent to phenyl ring), 3.8
(m, 1H, OH–CH), 5.35 (m, 1H, Ar–CH–O), 6.79–6.92
(m, 5H, ArH ortho to O, ArH ortho para to Cl), 7.26–
7.45 (m, 8H, ArH);IR (Neat): 3432, 2958, 2830, 1723,
1595, 1454, 1326, 1250, 1117, 759 cmꢀ1. Anal. Calcd
for C30H35ClF3N3O2Æ3HClÆ0.5H2O: C, 52.94;H, 5.74;
N, 6.18. Found: C, 52.64;H, 6.00;N, 6.56.
5.1.5.10. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-(2-phenethylamino)pr-
opan-2-ol (16). With 2-phenylethylamine (6j). Yield 65%;
MS (FAB) m/z: 487 ([M+1]+, 100%); 1H NMR
(200 MHz, CDCl3): d 2.01–2.21 (m, 2H, MeNCH2–
CH2), 2.26–2.41 (m, 4H, NMe, NCH2), 2.47–2.69 (m,
4H, NCH2), 2.75–2.82 (m, 4H, ArCH2, NCH2), 3.69–
3.73 (m, 1H, OH–CH), 5.19–5.27 (m, 1H, Ar–CH–O),
6.86–6.90 (d, 2H, J = 8.56 Hz, ArH ortho to O), 7.17–
7.32 (m, 5H, ArH), 7.39–7.44 (d, 2H, J = 8.66 Hz,
ArH ortho to CF3);IR (Neat): 3425, 2960, 1616, 1456,
1327, 1246, 1116, 759 cmꢀ1
.
Anal. Calcd for
C28H33F3N2O2Æ2HClÆ0.8H2O: C, 58.59;H, 6.38;N,
4.88. Found: C, 58.29;H, 6.61;N, 4.67.
5.1.5.7. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-[4-(4-methylphenyl)pi-
perazino]propan-2-ol
(13).
With
1-[(4-methyl)-
phenyl]piperazine (6g). Yield 75%;MS (FAB) m/z: 541
5.1.5.11. 1-[N-Methyl-N-(3-phenyl-3-(4-a,a,a-trifluo-
romethylphenoxy)propyl)amino]-3-cyclohexylaminoprop-
an-2-ol (17). With cyclohexylamine (6k). Yield 56%;MS
1
(M+, 100%); H NMR (200MHz, CDCl3): d 2.15–2.21
1
(m, 2H, MeNCH2–C H2), 2.26 (s, 3H, NMe), 2.33–
2.43 (m, 7H, ArCH3, NCH2), 2.55–2.71 (m, 6H,
NCH2), 3.10–3.15 (m, 4H, piperazinyl Hꢀs adjacent to
phenyl ring), 3.9 (m, 1H, OH–CH), 5.27–5.29 (m, 1H,
Ar–CH–O), 6.81–6.85 (d, 2H, J = 8.15Hz, ArH ortho
to N), 6.88–6.92 (d, 2H, J = 8.6Hz, ArH ortho to O),
7.05–7.09 (d, 2H, J = 8.16Hz, ArH ortho to CH3),
7.25–7.35 (m, 5H, ArH), 7.40–7.44 (d, 2H, J = 8.57Hz,
ArH ortho to CF3);IR (Neat): 3404, 2947, 2823, 1615,
1516, 1455, 1327, 1249, 1117, 758 cmꢀ1. Anal. Calcd
for C31H38F3N3O2Æ3HClÆ1.25H2O: C, 55.27;H, 6.46;
N, 6.24. Found: C, 54.99;H, 6.78;N, 6.37.
(FAB) m/z: 465 ([M+1]+, 100%); H NMR (200 MHz,
CDCl3): d 1.19–1.25 (m, 6H, cyclohexyl Hꢀs), 1.72 (m,
2H, cyclohexyl Hꢀs), 1.90–2.14 (m, 4H, cyclohexyl Hꢀs,
MeNCH2–CH2), 2.28 (s, 3H, NMe), 2.33–2.64 (m, 6H,
NCH2), 2.79 (m, 1H, NH–CH), 3.87–3.91 (m, 1H,
OH–CH), 5.22–5.28 (m, 1H, Ar–CH–O), 6.87–6.91 (d,
2H, J = 8.61 Hz, ArH ortho to O), 7.30–7.34 (m, 5H,
ArH), 7.40–7.44 (d, 2H, J = 8.65 Hz, ArH ortho to
CF3);IR (Neat): 3415, 2940, 2817, 2365, 1595,
1349 cmꢀ1. Anal. Calcd for C26H35F3N2O2Æ2HClÆ0.5-
H2O: C, 57.14;H, 6.96;N, 5.13. Found: C, 57.30;H,
7.28;N, 5.38.