P. Kocꢀalka et al. / Tetrahedron 62 (2006) 5763–5774
5771
73.92 (CH-30); 78.38 (C–Boc); 99.58 (CH-5); 153.61 (CO);
156.17 (CH-6); 164.17 (C-2); 165.46 (C-4).
aminopurine (27c) (2.3 g, 7.1 mmol) according to the proce-
dure described for compound 28a. Yield, 1.7 g (73%, white
powder).
4.2.8. (RS)-9-(3-Pyrrolidinyl)adenine dihydrochloride
(28a). (RS)-9-(N-tert-butoxycarbonyl-3-pyrrolidinyl)ade-
nine (27a) (3.0 g, 10 mmol) was treated with 20% (v/v)
TFA in DCM (100 mL) for 1 d. Pyrrolidine derivative was
deionized on Dowex 50 (H+ form) as described previously,
treated with 1 M HCl in MeOH (50 mL) for 30 min, and
the solution was concentrated in vacuo. Obtained solid resi-
due was co-evaporated several times with methanol and the
compound was freeze-dried from aqueous solution to give
dihydrochloride salt. Yield, 1.8 g (66%, white powder).
HRMS: for C9H14N7 (M+H)+ calcd 220.1311, found
220.1321.
nmax(KBr) 3318 (s, br), 3099 (s, vbr), 2942 (s, vbr, sh), 2738
(m, br), 1705 (s), 1686 (s, sh), 1636 (vs), 1612 (s), 1593 (s,
sh), 1570 (m, sh), 1532 (m, w), 1515 (w, sh), 1480 (m),
1414 (m), 1345 (m), 1205 (w), 790 (w), 658 (w).
1H NMR (400 MHz, DMSO-d6): 2.200 (dddd, 1H,
0
0
0
0
Jgem¼11.3, J4 b,5 ¼8.2, 6.9, J4 b,3 ¼4.4, H-4 b); 2.48 (dtd,
HRMS: for C9H13N6 (M+H)+ calcd 205.1202, found
205.1200.
1H, Jgem¼11.3, J4 a,3 ¼8.8, J4 a,5 ¼8.2, 6.6, H-4 a); 3.32
0
0
0
0
0
(br m, 1H, H-50b); 3.55 (br m, 1H, H-50a); 3.61 (br m, 2H,
H-20); 5.16 (tt, 1H, J3 ,4 ¼8.8, 4.4, J3 ,2 ¼6.8, 4.3, H-3 );
7.09 (br s, 2H, NH2); 8.09 (s, 1H, H-8); 8.10 (br s, 2H,
NH2); 9.52 and 9.96 (2ꢁbr s, 2H, NH).
0
0
0
0
0
nmax(KBr) 3350 (m), 3301 (s), 3119 (s, br), 2746 (w), 1674
(vs), 1647 (s), 1600 (vs),1570 (s), 1535 (m), 1480 (s),
1421 (s), 1415 (s), 1373 (s), 1331 (s), 1307 (s), 1229 (m),
845 (m), 798 (m), 728 (m).
13C NMR (100.6 MHz, DMSO-d6): 31.03 (CH2-40); 44.43
(CH2-50); 49.06 (CH2-20); 53.20 (CH-30); 112.20 (C-5);
138.89 (CH-8); 151.03 (C-4); 157.43 (C-6); 160.14 (C-2).
1H NMR (400 MHz, DMSO-d6): 2.34 (dddd, 1H, Jgem¼13.5,
0
0
0
0
0
J4 b,5 ¼8.1, 6.9, J4 b,3 ¼5.6, H-4 b); 2.49 (dtd, 1H, Jgem¼13.5,
0
0
0
0
0
J4 a,5 ¼8.2, 6.5, J4 a,3 ¼7.9, H-4 a); 3.30 (ddd, 1H, Jgem
¼
4.2.11. (RS)-1-(3-Pyrrolidinyl)thymine hydrochloride
(28d). The title compound was prepared from (RS)-1-(N-
tert-butoxycarbonyl-3-pyrrolidinyl)thymine (27d) (2.6 g,
8.8 mmol) according to the procedure described for com-
pound 28a. Yield, 1.2 g (73%, white powder).
0
0
0
11.5, J5 b,4 ¼8.2, 6.9, H-5 b); 3.51 (ddd, 1H, Jgem¼11.5,
J5 a,4 ¼8.1, 6.5, H-50a); 3.58 (dd, 1H, Jgem¼12.3,
0
0
0
0
0
0
0
J2 b,3 ¼5.4, H-2 b); 3.64 (dd, 1H, Jgem¼12.3, J2 a,3 ¼7.4, H-
20a); 5.25 (tt, 1H, J3 ,4 ¼7.9, 5.6, J3 ,2 ¼7.4, 5.4, H-3 ); 7.31
0
0
0
0
0
(br s, 2H, NH2); 8.15 (s, 1H, H-2); 8.31 (s, 1H, H-8).
HRMS: for C9H14N3O2 (M+H)+ calcd 196.1086, found
196.1095.
13C NMR (100.6 MHz, DMSO-d6): 30.69 (CH2-40); 44.48
(CH2-50); 49.10 (CH2-20); 53.26 (CH-30); 119.28 (C-5);
139.81 (CH-8); 149.25 (C-4); 152.53 (CH-2); 156.30 (C-6).
nmax(KBr) 3331 (m), 3064 (m), 1694 (vs), 1673 (vs), 1649
(vs), 1605 (m, sh), 1481 (s), 1438 (s, sh), 1398 (s), 1379
(m), 1275 (s), 760 (m).
4.2.9. (RS)-9-(3-Pyrrolidinyl)guanine dihydrochloride
(28b). The title compound was prepared from (RS)-9-(N-
tert-butoxycarbonyl-3-pyrrolidinyl)-guanine (27b) (1.5 g,
4.7 mmol) according to the procedure described for com-
pound 28a. Yield, 1.2 g (84%, white powder).
1H NMR (400 MHz, DMSO-d6): 1.78 (d, 3H, J¼1.2, CH3-
0
0
0
0
5); 2.10 (dq, 1H, Jgem¼13.3, J4 b,5 ¼8.9, 7.4, J4 b,3 ¼7.4,
H-40b); 2.31 (dtd, 1H, Jgem¼13.3, J4 a,3 ¼8.8, J4 a,5 ¼7.8,
4.7, H-40a); 3.17 (br m, 1H, H-50b); 3.32 (br m, 1H, H-
20b); 3.40–3.53 (br m, 2H, H-20a an0d H-50a); 5.02 (tdd, 1H,
0
0
0
0
HRMS: for C9H13N6O (M+H)+ calcd 221.1151, found
221.1154.
0
0
0
0
J3 ,2 ¼8.8, 6.3, J3 ,4 ¼8.8, 7.4, H-3 ); 7.77 (q, 1H, J¼1.2,
H-6); 7.48 (br s, 2H, +NH2); 11.36 (s, 1H, NH).
nmax(KBr) 3299 (m), 3112 (s, br), 2756 (m, br), 1720 (s),
1656 (vs), 1606 (s), 1536 (w), 1377 (m), 1162 (w), 766
(m), 732 (w), 674 (w).
13C NMR (100.6 MHz, DMSO-d6): 12.19 (CH3-5); 28.99
(CH2-40); 44.54 (CH2-50); 47.12 (CH2-20); 54.81 (CH-30);
109.61 (C-5); 139.09 (CH-6); 151.13 (C-2); 164.03 (C-4).
1H NMR (500 MHz, DMSO-d6): 2.31 (dddd, 1H, Jgem¼13.3,
0
0
0
0
0
J4 b,5 ¼8.2, 6.4, J4 b,3 ¼4.1, H-4 b); 2.54 (dtd, 1H, Jgem¼13.3,
4.2.12. (RS)-1-(3-Pyrrolidinyl)uracil hydrochloride
(28e). The title compound was prepared from (RS)-1-
(N-tert-butoxycarbonyl-3-pyrrolidinyl)uracil (27e) (1.2 g,
4.3 mmol) according to the procedure described for com-
pound 28a. Yield, 0.763 g (93%, yellow powder).
0
0
0
0
0
J4 a,3 ¼8.8, J4 a,5 ¼8.6, 6.8, H-4 a); 3.32 (ddd, 1H, Jgem
¼
0
0
0
0
11.9, J5 b,4 ¼8.6, 6.4, H-5 b); 3.54–3.73 (m, 3H, H-4 and
H-50a); 5.22 (tt, 1H, J3 ,4 ¼8.8, 4.1, J3 ,2 ¼7.4, 3.9, H-3 );
7.23 (br s, 2H, NH2); 8.82 (s, 1H, H-8); 9.25, 9.83 and
11.56 (3ꢁbr s, 3ꢁ1H, NH).
0
0
0
0
0
HRMS: for C8H12N3O2 (M+H)+ calcd 182.0930, found
182.0939.
13C NMR (125.8 MHz, DMSO-d6): 31.63 (CH2-40); 44.74
(CH2-50); 49.19 (CH2-20); 54.83 (CH-30); 111.00 (C-5);
136.92 (CH-8); 149.81 (C-4); 154.77 (C-6); 155.25 (C-2).
nmax(KBr) 3339 (s), 3089 (m), 3054 (m), 1766 (m), 1695 (vs,
vbr), 1625 (s), 1531 (m), 1408 (s), 992 (m).
4.2.10. (RS)-2,6-Diamino-9-(3-pyrrolidinyl)purine tri-
hydrochloride (28c). The title compound was prepared
from (RS)-9-(N-tert-butoxycarbonyl-3-pyrrolidinyl)-2,6-di-
1H NMR (400 MHz, DMSO-d6): 1.66 (dddd, 1H, Jgem¼13.3,
0
0
0
0
0
J4 b,5 ¼8.1, 6.8, J4 b,3 ¼4.4, H-4 b); 2.11 (dtd, 1H, Jgem¼13.3,