C. Lambertucci et al. / Bioorg. Med. Chem. 17 (2009) 2812–2822
2819
3.97 (d, 2H, J = 7.3 Hz, CH2), 7.22 (br s, 2H, NH2), 8.14 (s, 2H, H-2
and H-8). Anal. Calcd for C9H13N5: C, 56.53; H, 6.85; N, 36.62.
Found: C, 56.83; H, 6.99; N, 36.49.
4.35 (t, 2H, J = 5.1 Hz, CH2 N), 5.10 (t, 1H, J = 5.5 Hz, OH), 7.76 (s,
1H, H-2), 7.86 (br s, 2H, NH2), 8.23 (s, 1H, H-8). Anal. Calcd for
C7H9N5O: C, 46.92; H, 5.06; N, 39.09. Found: C, 47.16; H, 5.36; N,
38.96.
4.1.1.11. 7-Isobutyl-7H-adenine (7a). Mp: 227–230 °C; 1H NMR
(DMSO-d6) d 0.87 (d, 6H, J = 6.8 Hz, CH(CH3)2), 2.39 (m, 1H, CH),
4.12 (d, 2H, J = 7.3 Hz, CH2), 7.76 (s, 1H, H-2), 7.94 (br s, 2H,
NH2), 8.33 (s, 1H, H-8). Anal. Calcd for C9H13N5: C, 56.53; H, 6.85;
N, 36.62. Found: C, 56.75; H, 7.15; N, 36.45.
4.1.1.21. 9-(3-Hydroxypropyl)-9H-adenine (16). Mp: 218–
220 °C (lit.38 mp: 209–210 °C); 1H NMR (DMSO-d6) d 1.91 (m, 2H,
CH2CH2OH), 3.35 (m, 2H, CH2OH), 4.17 (t, 2H, J = 7.0 Hz, CH2 N),
4.64 (t, 1H, J = 5.2 Hz, OH), 7.18 (br s, 2H, NH2), 8.09 (s, 1H, H-8),
8.10 (s, 1H, H-2). Anal. Calcd for C8H11N5O: C, 49.73; H, 5.74; N,
36.25. Found: C, 49.85; H, 5.92; N, 36.11.
4.1.1.12. 9-Butyl-9H-adenine (8). Mp: 131–133 °C (lit.25 mp:
138–139 °C); 1H NMR (DMSO-d6) d 0.87 (t, 3H, J = 7.2 Hz, CH3),
1.22 (m, 2H, CH2CH3), 1.76 (m, 2H, CH2CH2CH2), 4.11 (t, 2H,
J = 7.0 Hz, CH2 N), 7.15 (br s, 2H, NH2), 8.11 (s, 1H, H-2 and H-8).
Anal. Calcd for C9H13N5: C, 56.53; H, 6.85; N, 36.62. Found: C,
56.62; H, 6.92; N, 36.55.
4.1.1.22. 7-(3-Hydroxypropyl)-7H-adenine (16a). Mp: 246–
249 °C (lit.35 mp: 201–203 °C); 1H NMR (DMSO-d6) d 2.02 (m, 2H,
CH2CH2OH), 3.39 (m, 2H, CH2OH), 4.37 (t, 2H, J = 6.9 Hz, CH2 N),
4.85 (t, 1H, J = 5.2 Hz, OH), 7.76 (s, 1H, H-2), 7.87 (br s, 2H, NH2),
8.31 (s, 1H, H-8). Anal. Calcd for C8H11N5O: C, 49.73; H, 5.74; N,
36.25. Found: C, 49.99; H, 5.81; N, 36.10.
4.1.1.13. 9-But-3-enyl-9H-adenine (9). Mp: 167–169 °C (lit.40
mp: 169–171 °C); 1H NMR (DMSO-d6) d 2.60 (m, 2H, CH2CH),
4.22 (t, 2H, J = 7.0 Hz, CH2N), 5.50 (m, 2H, CH@CH2), 5.80 (m, 1H,
CH@CH2), 7.20 (br s, 2H, NH2), 8.13 (s, 1H, H-8), 8.15 (s, 1H, H-2).
Anal. Calcd for C9H11N5: C, 57.13; H, 5.86; N, 37.01. Found: C,
57.50; H, 6.01; N, 36.75.
4.1.1.23. 9-(2-Hydroxypropyl)-9H-adenine (17). Mp: 192–
193 °C32 1H NMR (DMSO-d6) d 1.05 (d, 3H, J = 5.8 Hz, CH3), 4.06
;
(m, 3H, CHOH and CH2N), 5.04 (d, 1H, J = 3.07 Hz, OH), 7.21 (br s,
2H, NH2), 8.05 (s, 1H, H-8), 8.13 (s, 1H, H-2). Anal. Calcd for
C8H11N5O: C, 49.73; H, 5.74; N, 36.25. Found: C, 50.01; H, 5.89;
N, 36.01.
4.1.1.14. 9-Cyclopropyl-9H-adenine (10). Mp: 232–234 °C; 1H
NMR (DMSO-d6) d 1.06 (m, 4H, H cyclopropyl), 3.45 (m, 1H, H-1
cyclopropyl), 7.36 (br s, 2H, NH2), 8.15 (s, 1H, H-8), 8.18 (s, 1H,
H-2). Anal. Calcd for C8H9N5: C, 54.85; H, 5.18; N, 39.98. Found:
C, 54.93; H, 5.36; N, 39.73.
4.1.1.24. 7-(2-Hydroxypropyl)-7H-adenine (17a). Mp: 233 °C
(dec); 1H NMR (DMSO-d6) d 1.13 (d, 3H, J = 6.3 Hz CH3), 4.05 (m,
1H, H–CHN), 4.12 (m, 1H, CHOH), 4.33 (m, 1H, H–CHN), 5.15 (d,
1H, J = 5.1 Hz, OH), 7.74 (s, 1H, H-2), 7.85 (br s, 2H, NH2), 8.20 (s,
1H, H-8). Anal. Calcd for C8H11N5O: C, 49.73; H, 5.74; N, 36.25.
Found: C, 49.88; H, 5.92; N, 36.05.
4.1.1.15. 9-Cyclobutyl-9H-adenine (11). Mp: 163–165 °C (lit.41
mp: 175–178 °C); 1H NMR (DMSO-d6) d 1.86 (m, 2H, H cyclobutyl),
2.43 (m, 2H, H cyclobutyl), 2.67 (m, 2H, H cyclobutyl), 4.97 (m, 1H,
H-1 cyclobutyl), 7.21 (br s, 2H, NH2), 8.13 (s, 1H, H-2), 8.32 (s, 1H,
H-8). Anal. Calcd for C9H11N5: C, 57.13; H, 5.86; N, 37.01. Found: C,
57.42; H, 6.15; N, 36.81.
4.1.1.25. 9-(2,3-Dihydroxypropyl)-9H-adenine (18). Mp: 205–
207 °C; 1H NMR (DMSO-d6) d 3.31 (m, 2H, CH2OH), 3.80 (m, 1H
CHOH), 3.97 (m, 1H, H–CHN), 4.27 (m, 1H, H–CHN), 4.83 (t, 1H,
J = 6.0 Hz, CH2–OH), 5.08 (d, 1H, J = 5.1 Hz, CHOH), 7.17 (br s, 2H,
NH2), 8.01 (s, 1H, H-8), 8.10 (s, 1H, H-2). Anal. Calcd for
C8H11N5O2: C, 45.93; H, 5.30; N, 33.48. Found: C, 46.15; H, 5.72;
N, 33.27.
4.1.1.16. 9-Cyclopentyl-9H-adenine (12). Mp: 153–155 °C25 1H
;
NMR (DMSO-d6) d 1.68 (m, 2H, H cyclopentyl), 1.88 (m, 2H, H
cyclopentyl), 2.00 (m, 2H, H cyclopentyl), 2.13 (m, 2H, H cyclopen-
tyl), 4.82 (m, 1H, H-1 cyclopentyl), 7.19 (br s, 2H, NH2), 8.12 (s, 1H,
H-2), 8.20 (s, 1H, H-8). Anal. Calcd for C10H13N5: C, 59.10; H, 6.45;
N, 34.46. Found: C, 59.33; H, 6.55; N, 34.31.
4.1.1.26. 7-(2,3-Dihydroxypropyl)-7H-adenine (18a). Vitreous
solid; 1H NMR (DMSO-d6) d 3.35 (m, 2H, CH2OH), 3.95 (m, 1H
CHOH), 4.12 (m, 1H, H–CHN), 4.50 (m, 1H, H–CHN), 5.14 (t, 1H,
J = 6.0 Hz, CH2OH), 5.24 (d, 1H, J = 5.4 Hz, CHOH), 7.75 (s, 1H, H-
2), 7.87 (br s, 2H, NH2), 8.19 (s, 1H, H-8). Anal. Calcd for
C8H11N5O2: C, 45.93; H, 5.30; N, 33.48. Found: C, 46.12; H, 5.62;
N, 33.19.
4.1.1.17. 9-Cyclohexyl-9H-adenine (13). Mp: 199–201 °C25 1H
;
NMR (DMSO-d6) d 1.27 (m, 1H, H cyclohexyl), 1.44 (m, 2H, H cyclo-
hexyl), 1.71 (m, 1H, H cyclohexyl), 1.90 (m, 6H, H cyclohexyl), 4.34
(m, 1H, H-1 cyclohexyl), 7.18 (br s, 2H, NH2), 8.12 (s, 1H, H-2), 8.22
(s, 1H, H-8). Anal. Calcd for C11H15N5: C, 60.81; H, 6.96; N, 32.23.
Found: C, 60.95; H, 7.20; N, 32.01.
4.1.1.27. 9-Benzyl-9H-adenine (19). Mp: 205–207 °C (lit.50 mp:
233–236 °C); 1H NMR (DMSO-d6) d 5.37 (s, 2H, CH2), 7.25 (br s,
2H, NH2); 7.33 (m, 5H, H–Ph), 8.15 (s, 1H, H-2), 8.26 (s, 1H, H-8).
Anal. Calcd for C12H11N5: C, 63.99; H, 4.92; N, 31.09. Found: C,
64.13; H, 5.23; N, 31.00.
4.1.1.18. 9-Cycloheptyl-9H-adenine (14). Mp: 182–183 °C (lit.31
mp: 173–174 °C); 1H NMR (DMSO-d6) d 1.53 (m, 6H, H cyclohep-
tyl), 1.73 (m, 2H, H cycloheptyl), 2.00 (m, 4H, H cycloheptyl),
4.50 (m, 1H, H-1 cycloheptyl), 7.14 (br s, 2H, NH2), 8.10 (s, 1H,
H-2), 8.20 (s, 1H, H-8). Anal. Calcd for C12H17N5: C, 62.31; H,
7.41; N, 30.28. Found: C, 62.55; H, 7.62; N, 30.14.
4.1.1.28. 7-Benzyl-7H-adenine (19a). Mp: > 250 °C; 1H NMR
(DMSO-d6) d 5.51 (s, 2H, CH2), 7.33 (m, 3H, H–Ph), 7.46 (d, 2H,
J = 7.8 Hz, H–Ph), 7.75 (s, 1H, H-2), 7.92 (br s, 2H, NH2), 8.55 (s,
1H, H-8 Anal. Calcd for C12H11N5: C, 63.99; H, 4.92; N, 31.09.
Found: C, 64.36; H, 5.22; N, 30.82.
4.1.1.19. 9-(2-Hydroxyethyl)-9H-adenine (15). Mp: 237–
239 °C32 1H NMR (DMSO-d6) d 3.75 (m, 2H, CH2OH), 4.19 (t, 2H,
;
J = 5.5 Hz, CH2 N), 5.02 (t, 1H, J = 5.4 Hz, OH), 7.19 (br s, 2H, NH2),
8.03 (s, 1H, H-8), 8.14 (s, 1H, H-2). Anal. Calcd for C7H9N5O: C,
46.92; H, 5.06; N, 39.09. Found: C, 47.23; H, 5.41; N, 38.82.
4.1.1.29. 9-Phenylethyl-9H-adenine (20). Mp: 183–185 °C (lit.51
mp: 179–180 °C); 1H NMR (DMSO-d6) d 3.11 (t, 2H, J = 7.0 Hz,
CH2Ph), 4.36 (t, 2H, J = 7.2 Hz, CH2N), 7.18 (m, 7H, H–Ph and NH2),
7.90 (s, 1H, H-8), 8.12 (s, 1H, H-2). Anal. Calcd for C13H13N5: C,
65.25; H, 5.48; N, 29.27. Found: C, 65.55; H, 5.71; N, 29.16.
4.1.1.20. 7-(2-Hydroxyethyl)-7H-adenine (15a). Mp: > 250 °C
(lit.22 mp: 132–133 °C); 1H NMR (DMSO-d6) d 3.82 (m, 2H, CH2OH),