New Aryl-substituted Tandospirone and Epiboxidine Analogues
49
1.41–1.48 (m, 2H, β-CH2), 1.50–1.57 (m, 2H, γ -CH2), 1.88 (dt, 1H, J = 5.1, 12.8 Hz,
H6n), 2.15 (dd, 1H, J = 8.8, 12.8 Hz, H6x), 2.33 (t, 2H, J = 7.1 Hz, δ-CH2), 2.43 (t, 4H, J
= 4.8 Hz, Hpiperazine), 2.90 (d, 1H, J = 6.9 Hz, H2), 2.93–2.96 (m, 2H, H3 and H5n), 3.43 (t,
2H, J = 7.1 Hz, α-CH2), 3.76 (t, 4H, J = 4.8 Hz, Hpiperazine), 4.70 (s, 1H, H4), 4.93 (d, 1H,
J = 5.2 Hz, H1), 6.40 (t, 1H, J = 4.7 Hz, Hpyrimidine), 7.12–7.17 (m, 2H, Har), 7.20–7.23 (m,
3H, Har), 8.22 (d, 2H, J = 4.7 Hz, Hpyrimidine). 13C NMR (125 MHz, CDCl3): δ 23.61, 25.51,
38.82, 40.06, 43.46, 47.33, 49.63, 50.03, 52.95 (N–C), 57.91 (N–C), 79.15 (O–C), 84.81
(O–C), 109.87 (Cpyrimidine), 126.84 (Csubst), 127.11 (Csubst), 128.67 (Csubst), 144.08 (Csubst),
157.71 (Cpyrimidine), 161.60 (Cpyrimidine), 176.77 (C=O), 177.08 (C=O). FTIR (ATR): ν
2992, 2942, 2857, 1773, 1696, 1672, 1584 cm−1. LC-MS (ESI): 462.3 [M+1].
Anal. Calcd for C26H31N5O3: C, 67.66; H, 6.77; N, 15.17. Found: C, 67.65; H, 6.78;
N, 15.16.
5-exo-(4-Chlorophenyl)-N-[4-((4-pyrimidin-2-yl)piperazin-1-yl)butyl]-7-oxabicyclo
[2.2.1]heptane-2-exo,3-exo-dicarboximide (6c)
The reductive Heck procedure described above was used to prepare 292 mg (59%) of
1
6c, mp. 165◦C. Rf = 0.27 (20:1/chloroform:methanol). H NMR (500 MHz, CDCl3):
δ 1.48–1.55 (m, 2H, β-CH2), 1.59–1.65 (m, 2H, γ -CH2), 1.90 (dt, 1H, J = 5.1, 12.8 Hz,
H6n), 2.34 (dd, 1H, J = 8.8, 12.8 Hz, H6x), 2.40 (t, 2H, J = 7.1 Hz, δ-CH2), 2.50 (t, 4H,
J = 4.8 Hz, Hpiperazine), 2.97 (d, 1H, J = 6.9 Hz, H2), 2.99–3.03 (m, 2H, H3 and H5n), 3.51
(t, 2H, J = 7.1 Hz, α-CH2), 3.84 (t, 4H, J = 4.8 Hz, Hpiperazine), 4.74 (s, 1H, H4), 5.01 (d,
1H, J = 5.2 Hz, H1), 6.48 (t, 1H, J = 4.7 Hz, Hpyrimidine), 7.18 (d, 2H, J = 8.7 Hz, Har),
7.26 (d, 2H, J = 8.7 Hz, Har), 8.30 (d, 2H, J = 4.7 Hz, Hpyrimidine). 13C NMR (125 MHz,
CDCl3): δ 23.63, 25.49, 38.86, 40.12, 43.50, 46.74, 49.57, 49.90, 52.96 (N–C), 57.89 (N–C),
79.09 (O–C), 84.69 (O–C), 109.85 (Cpyrimidine), 128.48 (Csubst), 128.77 (Csubst), 132.64
(Csubst), 142.60 (Csubst), 157.69 (Cpyrimidine), 161.55 (Cpyrimidine), 176.59 (C=O), 176.87
(C=O). FTIR (ATR): ν 2940, 2861, 2817, 1763, 1689, 1582 cm−1. LC-MS (ESI): 496.3
[M+1].
Anal. Calcd for C26H30ClN5O3: C, 62.96; H, 6.10; N, 14.12. Found: C, 62.94; H, 6.11;
N, 14.13.
5-exo-(6-Chloropyridin-3-yl)-N-[4-((4-pyrimidin-2-yl)piperazin-1-yl)butyl]-
7-oxabicyclo[2.2.1]heptane-2-exo,3-exo-dicarboximide (6d)
The reductive Heck procedure described above was used to prepare 263 mg (53%) of 6d,
1
mp. 176–178◦C. Rf = 0.31 (20:1/chloroform:methanol). H NMR (500 MHz, CDCl3): δ
1.49–1.55 (m, 2H, β-CH2), 1.60–1.66 (m, 2H, γ -CH2), 1.88 (dt, 1H, J = 5.1, 12.8 Hz,
H6n), 2.30 (dd, 1H, J = 8.8, 12.8 Hz, H6x), 2.41 (t, 2H, J = 7.1 Hz, δ-CH2), 2.50 (t, 4H,
J = 4.8 Hz, Hpiperazine), 3.01 (d, 1H, J = 6.9 Hz, H2), 3.05–3.08 (m, 2H, H3 and H5n), 3.53
(t, 2H, J = 7.1 Hz, α-CH2), 3.84 (t, 4H, J = 4.8 Hz, Hpiperazine), 4.75 (s, 1H, H4), 5.05 (d,
1H, J = 5.2 Hz, H1), 6.49 (t, 1H, J = 4.7 Hz, Hpyrimidine), 7.29 (d, 1H, J = 8.4 Hz, Har), 7.62
(d, 1H, J = 8.4 Hz, Har), 8.26 (d, 1H, J = 2.5 Hz, Har), 8.31 (d, 2H, J = 4.7 Hz, Hpyrimidine).
13C NMR (125 MHz, CDCl3): δ 23.68, 25.49, 38.95, 40.07, 43.53, 44.10, 49.50, 49.74,
52.98 (N–C), 57.89 (N–C), 79.01 (O–C), 84.39 (O–C), 109.86 (Cpyrimidine), 124.52 (Csubst),
137.22 (Csubst), 138.54 (Csubst), 148.52 (Csubst), 150.18 (Csubst), 157.69 (Cpyrimidine), 161.63
(Cpyrimidine), 176.25 (C=O), 176.55 (C=O) ppm. FTIR (ATR): ν 2942, 2847, 1768, 1691,
1582 cm−1. LC-MS (ESI): 497.3 [M+1].