5528 J ournal of Medicinal Chemistry, 2003, Vol. 46, No. 25
Orjales et al.
(m, 2H), 2.60 (m, 2H), 2.14-1.97 (m, 2H), 1.47-1.26 (m, 3H);
13C NMR (CDCl3) δ 159.8, 138.4, 133.8, 133.4, 128.4, 127.9,
126.6, 120.5, 116.4, 113.9, 102.2, 85.4, 46.2, 46.1, 43.1, 29.2.
Anal. (C19H20N2O‚C2H2O4‚H2O) C, H, N.
4-[(Bip h en -2-yloxy)p h en ylm et h yl]p ip er id in e h yd r o-
ch lor id e (15e): mp 84-87 °C; yield 75%; 1H NMR (CDCl3) δ
7.58 (d, J ) 8.4 Hz, 2H), 7.47-7.13 (m, 9H), 7.05 (t, J ) 7.6
Hz, 1H), 6.91 (t, J ) 7.4 Hz, 1H), 6.73 (d, J ) 8.1 Hz, 1H),
4.85 (d, J ) 6.1 Hz, 1H), 2.96 (m, 2H), 2.45 (m, 2H), 1.82-
1.67 (m, 2H), 1.37-1.08 (m, 4H); 13C NMR (CDCl3) δ 154.9,
139.7, 138.8, 131.5, 130.7, 129.7, 128.2, 128.1, 127.6, 127.4,
126.8, 126.7, 120.6, 114.1, 84.7, 46.4, 46.4, 43.4, 29.6, 29.1.
Anal. (C24H25NO‚HCl) C, H, N.
4-[(2-Ch lor oph en oxy)ph en ylm eth yl]piper idin e h em isu l-
fa te (15f): mp 123-125 °C; yield 75%; 1H NMR (CDCl3) δ
7.33-7.26 (m, 6H), 6.97 (t, J ) 5.8 Hz, 1H), 6.76 (t, J ) 5.8
Hz, 1H), 6.66 (d, J ) 8.2 Hz, 1H), 4.87 (d, J ) 6.4 Hz, 1H),
3.10 (m, 2H), 2.60 (m, 2H), 2.02 (m, 2H), 1.48-1.25 (m, 3H);
13C NMR (CDCl3) δ 153.5, 139.2, 130.0, 128.2, 127.6, 127.2,
126.6, 123.2, 120.9, 114.8, 85.0, 46.4, 46.4, 43.4, 29.5, 29.2.
Anal. (C18H20ClNO‚1/2H2SO4‚2H2O) C, H, N, S.
4-[(Bip h en -4-yloxy)p h en ylm et h yl]p ip er id in e h yd r o-
ch lor id e (15o): mp 130 °C (dec); yield 82%; 1H NMR
(CDCl3) δ 7.49-7.22 (m, 12H), 6.87 (d, J ) 8.7 Hz, 2H), 4.84
(d, J ) 6.4 Hz, 1H), 3.10 (m, 2H), 2.58 (m, 2H), 1.96 (m,
2H), 1.41-1.25 (m, 3H); 13C NMR (CDCl3) δ 157.9, 140.6,
139.9, 133.4, 128.5, 128.2, 127.8, 127.4, 126.6, 126.5, 126.4,
115.9, 84.3, 46.4, 46.4, 43.4, 29.6, 29.2. Anal. (C24H25NO‚HCl)
C, H, N.
4-[(4-Flu or oph en oxy)ph en ylm eth yl]piper idin e h em isu l-
fa te (15p ): mp 108-110 °C; yield 75%; 1H NMR (CDCl3) δ
7.38-7.20 (m, 5H), 6.84-6.68 (m, 4H), 4.70 (d, J ) 7.1 Hz,
1H), 3.22-3.06 (m, 2H), 2.70-2.54 (m, 2H), 2.08-1.22 (m, 5H);
13C NMR (CDCl3) δ 156.9 (d, J ) 248 Hz), 154.7, 139.6, 128.3,
127.6, 126.7, 116.9 (d, J ) 8 Hz), 115.5 (d, J ) 20.7 Hz), 85.0,
46.2, 46.1, 43.2, 29.1, 28.9. Anal. (C18H20FNO‚1/2H2SO4‚2H2O)
C, H, N, S.
4-[P h en yl(4-t r iflu or om et h ylp h en oxy)m et h yl]p ip er i-
d in e h em isu lfa te (15q): mp 128 °C (dec); yield 89%; 1H NMR
(CDCl3) δ 7.42 (d, J ) 8.5 Hz, 2H), 7.38-7.22 (m, 5H), 6.85 (d,
J ) 8.5 Hz, 2H), 4.84 (d, J ) 6 Hz, 1H), 3.24-3.02 (m, 2H),
2.72-2.54 (m, 2H), 2.08-1.86 (m, 2H), 1.56-1.32 (m, 3H); 13
C
NMR (CDCl3) δ 160.8, 139.1, 128.4, 127.8, 126.7 (d, J ) 3.95
Hz), 126.6 (d, J ) 1.5 Hz), 124.3 (q, J ) 269.7 Hz), 122.6 (q, J
) 32 Hz), 115.6, 84.5, 46.5, 46.5, 43.5, 29.6, 29.3. Anal.
(C19H20F3NO‚1/2H2SO4‚2H2O) C, H, N, S.
4-[(3-Iod op h en oxy)p h en ylm eth yl]p ip er id in e h em isu l-
1
fa te (15g): mp 127 °C (dec); yield 37%; H NMR (CDCl3) δ
7.37-7.15 (m, 7H), 6.89-6.71 (m, 2H), 4.76 (d, J ) 6.5 Hz,
1H), 3.08 (m, 2H), 2.54 (m, 2H), 1.97-1.92 (m, 2H), 1.35-1.25
(m, 3H); 13C NMR (CDCl3) δ 158.9, 139.2, 130.4, 129.6, 128.3,
127.6, 126.6, 125.3, 114.9, 94.1, 84.4, 46.4, 46.3, 43.4, 29.5, 29.2.
Anal. (C18H20INO.1/ 2H2SO4‚2H2O) C, H, N, S
4-[(4-Br om oph en oxy)ph en ylm eth yl]piper idin e h em isu l-
fa te (15r ): mp 99-103 °C; yield 75%; 1H NMR (CDCl3) δ
7.38-7.18 (m, 7H), 6.68 (d, J ) 7 Hz, 2H), 4.75 (d, J ) 5.7 Hz,
1H), 3.10 (m, 2H), 2.75 (m, 2H), 2.05-1.80 (m, 2H), 1.48-1.25
(m, 3H); 13C NMR (CDCl3) δ 157.4, 139.3, 131.9, 128.3, 127.6,
126.6, 117.6, 112.6, 84.5, 46.39, 46.36, 43.4, 29.5, 29.2. Anal.
(C18H20BrNO‚1/2H2SO4‚2H2O) C, H, N, S.
4-[(3-Br om oph en oxy)ph en ylm eth yl]piper idin e h em isu l-
fa te (15h ): mp 98 °C (dec); yield 75%; 1H NMR (CDCl3) δ
7.32-7.26 (m, 6H), 7.00-6.97 (m, 2H), 6.75-6.70 (m, 1H), 4.78
(d, J ) 6.4 Hz, 1H), 3.08 (m, 2H), 2.52 (m, 2H), 1.92 (m, 2H),
1.42-1.25 (m, 3H); 13C NMR (CDCl3) δ 158.8, 138.9, 129.8,
127.9, 127.2, 126.2, 123.2, 122.1, 118.9, 113.9, 84.2, 46.0, 43.0,
29.2, 28.9. Anal. (C18H20BrNO‚1/2H2SO4‚2H2O) C, H, N, S.
4-[P h en yl(3-t r iflu or om et h ylp h en oxy)m et h yl]p ip er i-
d in e h yd r och lor id e (15i): mp 58 °C (dec); yield 72%; 1H
NMR (CDCl3) δ 7.38-6.87 (m, 9H), 4.82 (d, J ) 6.5 Hz, 1H),
3.10 (m, 2H), 2.58 (m, 2H), 2.05-1.85 (m, 2H), 1.50-1.22 (m,
3H); 13C NMR (CDCl3) δ 158.4, 139.1, 131.5 (q, J ) 32 Hz),
129.7, 128.4, 127.7, 126.6, 123.8 (q, J ) 270.6 Hz), 118.6 (d, J
) 1.3 Hz), 117.1 (q, J ) 3.6 Hz), 113.0 (q, J ) 4 Hz), 84.7,
46.4, 46.4, 43.4, 29.6, 29.5, 29.3. Anal. (C19H20F3NO‚HCl) C,
H, N.
3-[P h en yl(p ip er id in -4-yl)m eth oxy]ben zon itr ile h yd r o-
ch lor id e (15k ): mp 82 °C (dec); yield 80%; 1H NMR (CDCl3)
δ 7.37-7.00 (m, 9H), 4.80 (d, J ) 6 Hz, 1H), 3.12 (m, 2H),
2.55 (m, 2H), 1.98-1.84 (m, 2H), 1.48-1.25 (m, 3H); 13C NMR
(CDCl3) δ 157.8, 137.6, 130.3, 129.0, 128.7, 126.5, 124.9, 120.7,
119.1, 118.5, 113.1, 83.5, 43.9, 43.7, 41.3, 25.2, 25.1. Anal.
(C19H20N2O‚HCl) C, H, N.
4-[(3-Ch lor oph en oxy)ph en ylm eth yl]piper idin e h em isu l-
fa te (15l): mp 101-104 °C; yield 90%; 1H NMR (CDCl3) δ
7.38-7.22 (m, 5H), 7.08 (t, J ) 7.8 Hz, 1H), 6.82 (m, 2H), 6.70
(m, 1H), 4.78 (d, J ) 5 Hz, 1H), 3.15 (m, 2H), 2.58 (m, 2H),
2.05-1.80 (m, 2H), 1.55-1.25 (m, 3H); 13C NMR (CDCl3) δ
159.0, 139.2, 134.4, 129.8, 128.2, 127.5, 126.5, 120.6, 116.3,
113.8, 84.4, 46.2, 46.2, 43.2, 29.33, 29.1. Anal. (C18H20ClNO‚
1/2H2SO4‚2H2O) C, H, N, S.
4-[(4-Nitr op h en oxy)p h en ylm eth yl]p ip er id in e h yd r o-
ch lor id e (15m ): mp 80 °C (dec); yield 80%; 1H NMR (CDCl3)
δ 8.08 (d, J ) 8.2 Hz, 2H), 7.40-7.19 (m, 5H), 6.86 (d, J ) 8.2
Hz, 2H), 4.90 (d, J ) 6.5 Hz, 1H), 3.10 (m, 2H), 2.58 (m, 2H),
1.97 (m, 2H), 1.50-1.22 (m, 3H); 13C NMR (CDCl3) δ 163.3,
141.1, 138.3, 128.5, 127.9, 126.5, 125.5, 115.5, 85.0, 46.2, 43.2,
29.3, 29.1. Anal. (C18H20N2O3‚HCl) C, H, N.
4-[(2-F lu or op h en oxy)(3-flu or op h en yl)m et h yl]p ip er i-
d in e h yd r och lor id e (15t): mp 90 °C (dec); yield 62%; 1H
NMR (CDCl3) δ 9.54-9.36 (bs, 2H), 7.36-7.25 (m, 1H), 7.12-
6.67 (m, 7H), 4.83 (d, J ) 7.8 Hz, 1H), 3.63-3.43 (m, 1H),
2.92-2.44 (m, 4H), 2.10-1.72 (m, 3H), 1.48-1.42 (m, 1H); 13
C
NMR (CDCl3) δ 162.9 (d, J ) 247.4 Hz), 153.1 (d, J ) 245.8
Hz), 145.3 (d, J ) 10.5 Hz), 141.1 (d, J ) 6.4 Hz), 130.3 (d, J
) 8.1 Hz), 124.1 (d, J ) 3.9 Hz), 122.4 (d, J ) 7.1 Hz), 117.5
(d, J ) 1.4 Hz), 116.3 (d, J ) 18.3 Hz), 115.5 (d, J ) 21.0 Hz),
113.7 (d, J ) 22.2 Hz), 84.3, 43.8, 43.6, 41.0, 25.5, 25.0. Anal.
(C18H20F2NO‚HCl) C, H, N.
4-[(3-F lu or op h en oxy)(3-flu or op h en yl)m et h yl]p ip er i-
d in e h em isu lfa te (15u ): mp 158 °C (dec); yield 50%; 1H NMR
(CDCl3) δ 9.35-8.68 (bs, 1H), 7.16-6.64 (m, 5H), 6.41-6.27
(m, 3H), 4.86 (bs, 1H), 3.15 (m, 2H), 2.86-2.43 (m, 2H), 1.98-
1.42 (m, 4H), 1.35-1.22 (m, 1H); 13C NMR (CDCl3) δ 162.7 (d,
J ) 245.1 Hz), 162.3 (d, J ) 247.1 Hz), 158.6 (d, J ) 11.6 Hz),
141.2 (d, J ) 10.5 Hz), 129.8 (d, J ) 4.0 Hz), 129.7 (d, J ) 4.5
Hz), 122.2, 114.6 (d, J ) 21.1 Hz), 113.1 (d, J ) 21.6 Hz), 111.1
(d, J ) 3.0 Hz), 107.4 (d, J ) 21.1 Hz), 103.1 (d, J ) 23.6 Hz),
82.1, 43.2, 43.0, 40.3, 24.7, 24.5. Anal. (C18H19F2NO‚1/2H2SO4)
C, H, N.
4-[(3-F lu or op h en oxy)(4-m eth ylp h en yl)m eth yl]p ip er i-
d in e h yd r och lor id e (15v): mp 88 °C (dec); yield 67%; 1H
NMR (CDCl3) δ 9.51-9.38 (m, 2H), 7.20-7.01 (m, 5H), 6.60-
6.49 (m, 3H), 4.77 (d, J ) 6.7 Hz, 1H), 3.60-3.43 (m, 2H),
2.95-2.78 (m, 2H), 2.30 (s, 4H), 1.96-1.51 (m, 3H), 1.45-1.26
(m, 1H); 13C NMR (CDCl3) δ 163.2 (d, J ) 244.9 Hz), 159.2,
159.0, 138.0, 135.3, 129.9 (d, J ) 10.3 Hz), 129.4, 126.4, 111.5
(d, J ) 2.8 Hz), 107.7 (d, J ) 21.4 Hz), 103.6 (d, J ) 24.9 Hz),
83.2, 43.8, 43.7, 41.2, 25.2,25.1, 21.0. Anal. (C19H22FNO‚HCl)
C, H, N.
4-[(4-F lu or op h en oxy)(3-flu or op h en yl)m et h yl]p ip er i-
d in e h yd r och lor id e (15x): mp 65 °C (dec); yield 30%; 1H
NMR (CDCl3) δ 7.35-6.62 (m, 8H), 4.74 (d, J ) 6.5 Hz, 1H),
4-[(4-Iod op h en oxy)p h en ylm eth yl]p ip er id in e h em isu l-
1
fa te (15n ): mp 105 °C (dec); yield 57%; H NMR (CDCl3) δ
3.50-3.36 (m, 2H), 2.85-2.67 (m, 2H), 2.17-1.43 (m, 5H); 13
C
7.41 (d, J ) 8.9 Hz, 2H), 7.38-7.26 (m, 5H), 6.59 (d, J ) 8.9
Hz, 2H), 4.74 (d, J ) 6.5 Hz, 1H), 3.08 (m, 2H), 2.54 (m, 2H),
1.97-1.80 (m, 2H), 1.42-1.25 (m, 3H); 13C NMR (CDCl3) δ
158.2, 139.3, 137.9, 128.3, 127.6, 126.6, 118.2, 84.4, 82.6, 46.4,
46.4, 43.3, 29.5, 29.2. Anal. (C18H20INO‚1/2H2SO4‚2H2O) C, H,
N, S.
NMR (CDCl3) δ 162.9 (d, J ) 247.4 Hz), 157.3 (d, J ) 239.5
Hz), 153.7 (d, J ) 2.4 Hz), 141.7 (d, J ) 7.1 Hz), 130.2 (d, J )
8 Hz), 122.4 (d, J ) 3.0 Hz), 117.0 (d, J ) 8.0 Hz), 115.7 (d, J
) 23.3 Hz), 115.1 (d, J ) 21.0 Hz), 113.5 (d, J ) 21.8 Hz),
83.5, 44.3, 44.2, 41.6, 29.6, 26.0, 25.9. Anal. (C18H19F2NO‚HCl)
C, H, N.