(2 H, d, J 9.0), 8.00 (1 H, d, J 8.1), 11.37 (1 H, br s);
δC[(CD3)2SO] 15.0, 31.8, 33.2, 45.3, 45.6, 54.9, 61.6, 71.0, 72.5,
85.3, 86.4, 99.2, 102.6, 117.1, 121.8, 128.6, 140.7, 149.2, 150.8,
162.9.
propyldisiloxane-1,3-diyl)-6-N-pivaloyladenosine12 22a (11.85
g, 20 mmol) and 1-(4-chlorophenyl)-4-ethoxy-1,2,5,6-tetra-
hydropyridine 9 (R = Et, R1 = R2 = H, R3 = Cl) (6.94 g, 29.2
mmol) in the same way as for the corresponding uridine deriv-
ative 14 (R = Et, R1 = R2 = H, R3 = Cl); it was isolated as a
colourless solid (9.34 g, 79.5%) and crystallised from aq.
methanol (Found: C, 57.0; H, 6.3; N, 14.2. C28H37ClN6O6
requires C, 57.09; H, 6.33; N, 14.27%), mp 148–149 ЊC;
δH[(CD3)2SO] 0.53 (3 H, t, J 7.0), 1.29 (9 H, s), 1.62 (2 H, m),
1.81 (1 H, m), 1.91 (1 H, m), 2.55–2.75 (2 H, m), 2.99 (2 H, m),
3.25 (1 H, m), 3.36 (1 H, m), 3.64 (1 H, m), 3.77 (1 H, m), 4.07
(1 H, m), 4.21 (1 H, m), 5.01 (1 H, dd, J 4.8 and 7.1), 5.31 (1 H,
d, J 4.6), 5.39 (1 H, dd, J 4.9 and 6.5), 6.17 (1 H, d, J 7.2), 6.84
(2 H, d, J 9.1), 7.17 (2 H, d, J 9.0), 8.73 (1 H, s), 8.78 (1 H, s),
10.25 (1 H, s); δC[(CD3)2SO] 14.4, 26.8, 31.6, 32.2, 45.0, 45.7,
54.7, 61.7, 71.0, 72.6, 86.4, 87.1, 99.2, 117.1, 121.8, 126.2, 128.5,
143.4, 149.1, 150.8, 151.5, 151.8, 176.2.
2Ј-O-[4-(2-Acetoxyethoxy)-1-(2-chlorophenyl)piperidin-4-yl]-
uridine 20a
This compound was prepared from 3Ј,5Ј-O-(1,1,3,3-tetraiso-
propyldisiloxane-1,3-diyl)uridine 13 (6.004 g, 12.3 mmol) and
4-(2-acetoxyethoxy)-1-(2-chlorophenyl)-1,2,5,6-tetrahydro-
pyridine 19a (R1 = Cl, R2 = R3 = H) (5.471 g, 18.5 mmol) in the
same way as for the corresponding 2Ј-O-[1-(4-chlorophenyl)-4-
ethoxypiperidin-4-yl] derivative 14 (R = Et, R1 = R2 = H,
R3 = Cl) (see above); it was isolated as a colourless solid (5.58 g,
83%) following crystallisation from aq. methanol (Found: C,
52.1; H, 5.7; N 7.5. C24H30ClN3O9ؒ0.75 H2O requires C, 52.08;
H, 5.74; N, 7.59%), mp 159–161 ЊC; δH[(CD3)2SO] 1.80–2.0 (4
H, m), 2.01 (3 H, s), 2.75 (1 H, m), 2.88 (2 H, m), 3.04 (1 H, m),
3.35 (1 H, m), 3.59 (2 H, m), 3.73 (1 H, m), 3.93 (1 H, m), 4.04 (3
H, m), 4.38 (1 H, dd, J 5.0 and 7.2), 5.24 (2 H, m), 5.73 (1 H, d,
J 8.1), 6.03 (1 H, d, J 7.3), 7.02 (1 H, m), 7.08 (1 H, dd, J 1.1 and
8.0), 7.27 (1 H, m), 7.39 (1 H, dd, J 1.4 and 7.9), 7.98 (1 H, d,
J 8.1), 11.42 (1 H, br s); δC[(CD3)2SO] 20.6, 33.1, 34.2, 47.9,
48.4, 57.9, 61.5, 63.0, 70.7, 72.7, 85.5, 86.4, 99.3, 102.6, 120.8,
123.9, 127.7, 128.1, 130.3, 140.7, 149.1, 150.9, 162.9, 170.3.
2Ј-O-[1-(4-Chlorophenyl)-4-ethoxypiperidin-4-yl]adenosine 23
(B ؍
27, R ؍
Et, R1 ؍
R2 ؍
H, R3 ؍
Cl)
2Ј-O-[1-(4-Chlorophenyl)-4-ethoxypiperidin-4-yl]-6-N-pivaloyl-
adenosine 23a (R = Et, R1 = R2 = H, R3 = Cl) (1.004 g, 1.7
mmol) was dissolved in ethanolic methylamine (8 mol dmϪ3; 2
cm3) and the solution was stirred at room temperature. After
2 h, the products were evaporated under reduced pressure.
Crystallisation of the residue from methanol gave the title com-
pound 23 (B = 27, R = Et, R1 = R2 = H, R3 = Cl) (Found: C,
53.8; H, 5.8; N 16.3. C23H29ClN6O5ؒ0.5 H2O requires C, 53.75;
H, 5.88; N, 16.35%) (0.832 g, 96%), mp 163–164 ЊC; δH[(CD3)2-
SO] 0.48 (3 H, t, J 7.0), 1.60 (2 H, m), 1.75 (1 H, m), 1.88 (1 H,
m), 2.52 (1 H, m), 2.69 (1 H, m), 2.95 (1 H, m), 3.09 (1 H, m),
3.20 (1 H, m), 3.38 (1 H, m), 3.59 (1 H, m), 3.72 (1 H, m), 4.05
(1 H, s), 4.15 (1 H, t, J 4.3), 5.00 (1 H, dd, J 4.7 and 7.6), 5.23
(1 H, d, J 4.1), 5.90 (1 H, dd, J 3.8 and 8.5), 6.02 (1 H, d, J 7.6),
6.86 (2 H, d, J 9.1), 7.18 (2 H, d, J 9.0), 7.44 (2 H, br s), 8.16
(1 H, s), 8.42 (1 H, s); δC[(CD3)2SO] 14.2, 31.4, 33.4, 45.0, 45.6,
54.4, 62.1, 71.3, 72.3, 86.8, 87.4, 99.0, 117.0, 119.6, 121.8, 128.5,
140.3, 148.6, 149.1, 152.2, 156.2.
2Ј-O-[1-(2-Chlorophenyl)-4-(2-hydroxyethoxy)piperidin-4-yl]-
uridine 21
A solution of 2Ј-O-[4-(2-acetoxyethoxy)-1-(2-chlorophenyl)-
piperidin-4-yl]uridine 20a (0.50 g, 0.93 mmol) in ethanolic
methylamine (8 mol dmϪ3; 2.0 cm3) was stirred at room tem-
perature. After 2 h, the products were evaporated under
reduced pressure and the residue was crystallised from meth-
anol to give the title compound 21 (Found: C, 52.5; H, 5.6; N,
8.35. C22H28ClN3O8ؒ0.4H2O requires C, 52.3; H, 5.75; N,
8.32%) (0.408 g, 88%), mp 134–136 ЊC; δH[(CD3)2SO] 1.75–2.0
(4 H, m), 2.79 (1 H, m), 2.93 (2 H, m), 3.03 (1 H, m), 3.21 (1 H,
m), 3.41 (2 H, m), 3.51 (1 H, m), 3.59 (2 H, m), 3.93 (1 H, m),
4.05 (1 H, m), 4.38 (1 H, m), 4.66 (1 H, m), 5.22 (2 H, m), 5.74
(1 H, d, J 8.1), 6.03 (1 H, d, J 7.4), 7.02 (1 H, m), 7.10 (1 H, m),
7.27 (1 H, m), 7.39 (1 H, dd, J 1.3 and 7.9), 7.97 (1 H, d, J 8.1),
11.38 (1 H, br); δC[(CD3)2SO] 33.2, 34.3, 47.9, 48.3, 60.3, 61.6,
61.8, 70.9, 72.6, 85.4, 86.4, 99.1, 102.6, 120.9, 123.8, 127.6,
128.0, 130.3, 140.7, 149.1, 150.9, 162.9.
2Ј-O-[1-(2-Fluorophenyl)-4-methoxypiperidin-4-yl]adenosine 23
(B ؍
27, R ؍
Me, R1 ؍
F, R2 ؍
R3 ؍
H)
2Ј-O-[1-(2-Fluorophenyl)-4-methoxypiperidin-4-yl]-6-N-
pivaloyladenosine12 23a (R = Me, R1 = F, R2 = R3 = H) (0.50 g,
0.9 mmol) was converted into the title compound 23 (B = 27,
R = Me, R1 = F, R2 = R3 = H) (Found: C, 54.6; H, 5.5; N,17.25.
C22H27FN6O5ؒ0.5 H2O requires C, 54.65; H, 5.84; N, 17.38%)
(0.363 g, 85%) by the deacylation procedure described above
in the preparation of the corresponding 1-(4-chlorophenyl)-4-
ethoxypiperidin-4-yl derivative 23 (B = 27, R = Et, R1 = R2 = H,
R3 = Cl); mp 156–157 ЊC; δH[(CD3)2SO] 1.65 (2 H, m), 1.84
(1 H, m), 1.97 (1 H, m), 2.55 (1 H, m), 2.57 (3 H, s), 2.81 (2 H,
m), 3.09 (1 H, m), 3.60 (1 H, m), 3.72 (1 H, m), 4.06 (1 H, m),
4.19 (1 H, t, J 4.2), 5.01 (1 H, dd, J 4.6 and 7.7), 5.29 (1 H, d,
J 4.1), 5.71 (1 H, m), 6.06 (1 H, d, J 7.7), 6.92 (2 H, m), 7.08
(2 H, m), 7.43 (2 H, brs), 8.17 (1 H, s), 8.44 (1 H, s);
δC[(CD3)2SO] 31.9, 33.8, 46.4, 47.0, 47.6, 54.9, 62.0, 71.2, 72.4,
86.2, 87.3, 99.0, 115.7, 115.9, 119.4, 122.2, 124.7, 139.7, 139.8,
140.2, 149.0, 152.5, 153.5, 156.2.
2Ј-O-{1-(2-Chlorophenyl)-4-[2-(methoxyacetoxy)ethoxy]-
piperidin-4-yl}uridine 20b
This compound was prepared from 3Ј,5Ј-O-(1,1,3,3-tetraiso-
propyldisiloxane-1,3-diyl)uridine 13 (0.78 g, 1.6 mmol) and
1-(2-chlorophenyl)-4-[2-(methoxyacetoxy)ethoxy]-1,2,5,6-tetra-
hydropyridine 19b (R1 = Cl, R2 = R3 = H) (0.782 g, 2.4 mmol) in
the same way as for the corresponding 2Ј-O-[1-(4-chlorophenyl)-
4-ethoxypiperidin-4-yl] derivative 14 (R = Et, R1 = R2 = H,
R3 = Cl) (see above); it was isolated as a crystalline solid (0.832
g, 91%) following crystallisation from aq. methanol (Found: C,
52.7; H, 5.6; N, 7.2. C25H32ClN3O10 requires C, 52.68; H, 5.66,
N, 7.37%), mp 171–172 ЊC; δH[(CD3)2SO] 1.80–2.0 (4 H, m),
2.75 (1 H, m), 2.88 (2 H, m), 3.03 (1 H, m), 3.30 (3 H, s), 3.39
(1 H, m), 3.60 (2 H, m), 3.76 (1 H, m), 3.93 (1 H, m), 4.06 (3 H,
m), 4.12 (2 H, m), 4.38 (1 H, dd, J 5.1 and 7.0), 5.27 (2 H, m),
5.75 (1 H, d, J 8.1), 6.04 (1 H, d, J 7.2), 7.0–7.10 (2 H, m), 7.28
(1 H, m), 7.40 (1 H, dd, J 1.4 and 7.9), 8.00 (1 H, d, J 8.1), 11.44
(1 H br); δC[(CD3)2SO] 33.0, 34.0, 47.8, 48.2, 57.8, 58.4, 61.2,
63.1, 68.7, 70.4, 72.6, 85.5, 86.1, 99.2, 102.5, 120.7, 123.9, 127.6,
128.0, 130.2, 140.7, 148.9, 150.7, 162.9, 170.0.
4-N-Benzoyl-2Ј-O-[1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl]-
cytidine 23b (R ؍
Et, R1 ؍
R2 ؍
H, R3 ؍
Cl)
This compound was prepared from 4-N-benzoyl-3Ј,5Ј-O-
(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)cytidine12 22b (3.45
g, 5.85 mmol) and 1-(4-chlorophenyl)-4-ethoxy-1,2,5,6-tetra-
hydropyridine 9 (R = Et, R1 = R2 = H, R3 = Cl) (2.086 g, 8.8
mmol) in the same way as for the corresponding uridine deriv-
ative 14 (R = Et, R1 = R2 = H, R3 = Cl); it was isolated as a
colourless solid (2.97 g, 86%) and crystallised from aq. methanol
2Ј-O-[1-(4-Chlorophenyl)-4-ethoxypiperidin-4-yl]-6-N-pivaloyl-
adenosine 23a (R ؍
Et, R1 ؍
R2 ؍
H, R3 ؍
Cl)
This compound was prepared from 3Ј,5Ј-O-(1,1,3,3-tetraiso-
174
J. Chem. Soc., Perkin Trans. 1, 2000, 165–176