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M. Hocek et al.
PAPER
(C-5), 135.1 (Cipso), 142.6 (C-8), 152.4 (CH-2), 153.2 and 153.7 (C-
4 and C-6).
1H NMR (CDCl3, 500 MHz): d = 1.80–2.14 (m, 6 H, CH2), 3.77–
3.81 (m, 1 H, H-5¢a), 4.23–4.27 (m, 1 H, H-5¢b), 5.90 (dd, 1 H,
J = 10.8, 2.3 Hz, H-1¢), 6.18 (s, 2 H, NH2), 7.45–7.55 and 8.53–8.55
(m, 5 Harom), 8.74 (s, 1 H, H-2).
13C NMR (APT, CDCl3, 125.8 MHz): d = 22.4, 25.1 and 29.8 (CH2),
69.4 (CH2O), 82.7 (NCHO), 128.4, 129.1 and 129.7 (CHarom), 130.4
(C-5), 136.5 (Cipso), 149.0 (CH-2), 148.1, 152.4 and 154.6 (C-4, C-
6 and C-8).
HMBC cross-peaks: NCHO to C-4 and C-8, o-CHarom to C-6.
NOE: o-CHarom to CH-2.
EI-MS: m/z (%) = 314 (8), 231 (56), 85 (77), 41 (100).
EI-HRMS: m/z calcd for C16H15ClN4O: 314.0934; found: 314.0922.
6,8-Diphenyl-9-(tetrahydropyran-2-yl)purine (2b)4
Prepared from 1 (273 mg, 1 mmol) by Method B [4 equiv of
PhB(OH)2] in 67% yield (239 mg) or by Method B [1.1 equiv of
PhB(OH)2] in 11% yield (39 mg); colorless foam.
1H NMR (CDCl3, 500 MHz): d = 1.58–2.06 and 3.08–3.20 (m, 6 H,
CH2), 3.71 (br t, 1 H, J = 11.5 Hz, H-5¢a), 4.28 (br d, 1 H, J = 9.5
Hz, H-5¢b), 5.66 (d, 1 H, J = 11.0 Hz, H-1¢), 7.50–7.59, 7.94–7.97
and 8.85–8.88 (m, 10 Harom), 9.05 (s, 1 H, H-2).
13C NMR (APT, CDCl3, 127.8 MHz): d = 23.5, 24.7 and 28.6 (CH2),
69.0 (CH2O), 84.2 (NCHO), 128.6, 128.7, 129.9, 130.0, 130.7 and
130.8 (CHarom and overlapped Cipso), 135.9 (C-5), 151.9 (CH-2),
154.1, 154.2 and 155.4 (C-4, C-6 and C-8).
EI-MS: m/z (%) = 295 (10), 211 (100), 184 (10), 85 (15).
EI-HRMS): m/z calcd for C16H17N5O: 295.1433; found: 295.1414.
8-Methoxy-6-phenyl-9-(tetrahydropyran-2-yl)purine (2f)
Prepared from 2a (314 mg, 1 mmol) by Method D (methanolic am-
monia) in 58% yield (180 mg); colorless foam.
1H NMR (CDCl3, 500 MHz): d = 1.59–1.86, 2.08–2.12 and 2.83–
2.91 (m, 6 H, CH2), 3.72–3.78 (m, 1 H, H-5¢a), 4.17–4.20 (m, 1 H,
H-5¢b), 4.31 (s, 3 H, CH3), 5.67 (d, 1 H, J = 11.3 Hz, H-1¢), 7.45–
7.55 and 8.71–8.75 (m, 5 Harom), 8.87 (s, 1 H, H-2).
13C NMR (APT, CDCl3, 125.8 MHz): d = 23.4, 24.8 and 28.7 (CH2),
57.7 (CH3), 69.1 (CH2O), 81.6 (NCHO), 128.5, 129.3 and 130.2
(CHarom), 128.6 (C-5), 136.0 (Cipso), 150.6 (CH-2), 150.1, 153.0 and
157.9 (C-4, C-6 and C-8).
EI-MS: m/z (%) = 356 (8), 272 (100), 85 (28).
EI-HRMS: m/z calcd for C22H20N4O: 356.1637; found: 356.1640.
EI-MS: m/z (%) = 310 (9), 226 (100), 211 (24), 85 (26).
8-Methyl-6-phenyl-9-(tetrahydropyran-2-yl)purine (2c = 3b)
Prepared from 2a (314 mg, 1 mmol) by Method A (3 equiv of
MeMgCl) in 77% yield (226 mg) or from 3a (253 mg, 1 mmol) by
Method B [3 equiv of PhB(OH)2] in 88% yield (259 mg); colorless
crystals; mp 89–92 °C (CH2Cl2–heptane).
1H NMR (CDCl3, 500 MHz): d = 1.67–2.15 and 2.46–2.56 (m, 6 H,
CH2), 2.86 (s, 3 H, CH3), 3.79 (dt, 1 H, J = 11.7, 2.3 Hz, H-5¢a),
4.21 (br d, 1 H, J = 11.3 Hz, H-5¢b), 5.91 (dd, 1 H, J = 11.3, 2.4 Hz,
H-1¢), 7.50–7.59 (m, 3 Harom), 8.74–8.77 (m, 2 Harom), 8.97 (s, 1 H,
H-2).
13C NMR (APT, CDCl3, 100.6 MHz): d = 16.4 (CH3), 23.2, 25.0 and
30.4 (CH2), 69.2 (CH2O), 82.8 (NCHO), 127.9, 128.6 and 130.6
(CHarom), 130.2 (C-5), 135.9 (Cipso), 151.5 (CH-2), 153.1, 153.4 and
153.9 (C-8, C-4 and C-6). NOE: CH3 to NCHO.
EI-HRMS): m/z calcd for C17H18N4O2: 310.1430; found: 310.1433
6-Chloro-8-methyl-9-(tetrahydropyran-2-yl)purine (3a)4
Prepared from 1 (273 mg, 1 mmol) by Method A (1.1 equiv of
MeMgCl) in 37% yield (93 mg); colorless oil.
1H NMR (CDCl3, 400 MHz): d = 1.63–2.15 and 2.45–2.53 (m, 6 H,
CH2), 2.81 (s, 3 H, CH3), 3.74 (t, 1 H, J = 11.3 Hz, H-5¢a), 4.21 (d,
1 H, J = 10.6 Hz, H-5¢b), 5.79 (dd, 1 H, J = 11.2, 1.7 Hz, H-1¢), 8.67
(s, 1 H, H-2).
13C NMR (APT, CDCl3, 100.6 MHz): d = 16.3 (CH3), 23.1, 24.8 and
30.1 (CH2), 69.2 (CH2O), 83.3 (NCHO), 130.7 (C-5), 149.0 (C-6),
151.0 (CH-2), 152.6 (C-4), 155.2 (C-8).
NOE interaction: CH3 to NCHO.
EI-MS: m/z (%) = 294 (19), 210 (100), 85 (26).
HMBC cross-peaks: CH3 with C-8 and C-5, NCHO with C-4 and C-
8.
EI-HRMS: m/z calcd for C17H18N4O: 294.1481; found: 294.1482.
EI-MS: m/z (%) = 252 (8), 169 (26), 85 (100).
Anal. Calcd for C17H18N4O (294.4): C, 69.37; H, 6.16; N, 19.03.
Found: C, 69.13; H, 6.10; N, 18.79.
EI-HRMS): m/z calcd for C11H13ClN4O: 252.0778; found:
252.0782.
8-Benzyl-6-phenyl-9-(tetrahydropyran-2-yl)purine (2d)
Prepared from 2a (314 mg, 1 mmol) by Method C (3 equiv of Bn-
ZnCl) in 89% yield (330 mg); colorless oil.
1H NMR (CDCl3, 500 MHz): d = 1.55–1.64, 1.70–1.78, 1.93–1.99
and 2.37–2.45 (m, 6 H, CH2), 3.57–3.63 (m, 1 H, H-5¢a), 4.15–4.20
(m, 1 H, H-5¢b), 4.54 (dd, 2 H, J = 5.7, 14.4 Hz, CH2Ph), 5.68 (dd,
1 H, J = 11.1, 2.0 Hz, H-1¢), 7.24–7.35, 7.50–7.57 and 8.79–8.82
(m, 10Harom), 8.97 (s, 1 H, H-2).
13C NMR (APT, CDCl3, 127.8 MHz): d = 23.2, 24.8 and 29.9 (CH2),
35.7 (CH2Ph), 69.2 (CH2O), 82.7 (NCHO), 127.0, 128.6, 128.7,
129.8, 130.6 (CHarom and overlapped C-5), 135.9 and 136.1 (Cipso),
151.7 (CH-2), 153.5 (C-4 and C-6), 155.0 (C-8).
6,8-Dimethyl-9-(tetrahydropyran-2-yl)purine (3c)
Prepared from 1 (273 mg, 1 mmol) by Method A (9 equiv of
MeMgCl) in 90% yield (209 mg) or by Method A (1.1 equiv of
MeMgCl) in 14% yield (32 mg); colorless oil.
1H NMR (CDCl3, 400 MHz): d = 1.64–2.14 and 2.35–2.55 (m, 6 H,
CH2), 2.78 and 2.81 (2 s, 2 × 3 H, 2 × CH3), 3.75 (dd, 1 H,
J = 11.3, 9.5 Hz, H-5¢a), 4.21 (br d, 1 H, J = 10.3 Hz, H-5¢b), 5.80
(dd, 1 H, J = 11.1, 1.8 Hz, H-1¢); 8.77 (s, 1 H, H-2).
13C NMR (APT, CDCl3, 100.6 MHz): d = 16.2 and 19.3 (CH3), 23.2,
24.9 and 30.2 (CH2), 69.2 (CH2O), 82.8 (NCHO), 131.9 (C-5),
151.4 (CH-2), 153.2 and 157.1 (C-8, C-4 and C-6).
HMBC cross-peaks: CH2Ph with C-8 and C-4, NCHO with C-4.
EI-MS: m/z (%) = 370 (11), 286 (100), 210 (25), 85 (40).
EI-HRMS: m/z calcd for C23H22N4O: 370.1794; found: 370.1798.
EI-MS: m/z (%) = 232 (26), 149 (100), 85 (87).
EI-HRMS: m/z calcd for C12H16N4O: 232.1324; found: 232.1326.
6-Benzyl-8-methyl-9-(tetrahydropyran-2-yl)purine (3d)
Prepared from 3a (253 mg, 1 mmol) by Method C (3 equiv of Bn-
ZnCl) in 96% yield (296 mg); colorless oil.
1H NMR (CDCl3, 500 MHz): d = 1.62–1.67, 1.73–1.79, 1.87–1.96,
2.07–2.12 and 2.44–2.53 (m, 6 H, CH2), 2.80 (s, 3 H, CH3), 3.73 (dt,
8-Amino-6-phenyl-9-(tetrahydropyran-2-yl)purine (2e)
Prepared from 2a (314 mg, 1 mmol) by Method D (ethanolic ammo-
nia) in 69% yield (203 mg) or by Method D (methanolic ammonia)
in 34% yield (100 mg); colorless foam.
Synthesis 2004, No. 6, 889–894 © Thieme Stuttgart · New York