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Jꢁ7.5 Hz), 5.15 (2H, s), 5.40 (2H, s), 6.87 (2H, d, 7.41 (2H, d, Jꢁ9.0 Hz), 7.72 (1H, s), 12.50 (1H, br s).
Jꢁ8.5 Hz), 6.90—7.47 (6H, m), 7.50 (1H, s). IR (KBr)n : IR (KBr)n : 3425, 1705, 1662 cmꢂ1. Anal. Calcd for
1703, 1660 cmꢂ1. Anal. Calcd for C23H23N4O3Cl: C, 62.94; C15H15N4O2Cl: C, 56.52; H, 4.74; N, 17.58. Found: C, 56.47;
H, 5.28; N, 12.76. Found: C, 62.67; H, 5.24; N, 12.97.
3,7-Dihydro-1-(4-chlorobenzyl)-7-(4-methoxybenzyl)-3-
H, 4.68; N, 17.42.
3,7-Dihydro-1-(2-methylbenzyl)-3-propyl-1H-purine-2,4-
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propyl-1H-purine-2,4-dione (4c): Yield 70%. mp 133— dione (1d): Yield 57%. mp 198—199 °C. H-NMR (CDCl3)
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134 °C. H-NMR (CDCl3) d: 0.97 (3H, t, 3H, Jꢁ7.5 Hz), d : 0.97 (3H, t, 3H, Jꢁ7.4 Hz), 1.70 (2H, sext., Jꢁ7.4 Hz),
1.80 (2H, sext., Jꢁ7.5 Hz), 3.71 (3H, s), 4.06 (2H, t, 2.50 (3H, s), 4.13 (2H, t, Jꢁ7.4 Hz), 5.28 (2H, s), 6.90—7.15
Jꢁ7.5 Hz), 5.17 (2H, s), 5.35 (2H, s), 6.82 (2H, d, (4H, m), 7.58 (1H, s), 12.51 (1H, br s). IR (KBr)n : 3425,
Jꢁ8.5 Hz), 7.08—7.40 (4H, m), 7.45 (1H, s). IR (KBr)n: 1705, 1662 cmꢂ1. Anal. Calcd for C16H18N4O2: C, 64.41; H,
1707, 1666 cmꢂ1. Anal. Calcd for C23H23N4O3Cl: C, 62.94; 6.08; N, 18.78. Found: C, 64.14; H, 6.23; N, 18.84.
H, 5.28; N, 12.76. Found: C, 62.61; H, 5.19; N, 12.82.
3,7-Dihydro-1-(3-methylbenzyl)-3-propyl-1H-purine-2,4-
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3,7-Dihydro-1-(2-methylbenzyl)-7-(4-methoxybenzyl)-3- dione (1e): Yield 58%. mp 174—175 °C. H-NMR (CDCl3)
propyl-1H-purine-2,4-dione (4d): Yield 69%. mp 127— d : 0.97 (3H, t, 3H, Jꢁ7.4 Hz), 1.70 (2H, sext., Jꢁ7.4 Hz),
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128 °C. H-NMR (CDCl3) d: 0.97 (3H, t, 3H, Jꢁ7.5 Hz), 2.38 (3H, s), 4.10 (2H, t, Jꢁ7.4 Hz), 5.23 (2H, s), 6.95—7.40
1.70 (2H, sext., Jꢁ7.5 Hz), 2.42 (3H, s), 3.75 (3H, s), 4.07 (4H, m), 7.60 (1H, s), 12.60 (1H, br s). IR (KBr)n : 3425,
(2H, t, Jꢁ7.5 Hz), 5.20 (2H, s), 5.40 (2H, s), 6.86 (2H, 1709, 1664 cmꢂ1. Anal. Calcd for C16H18N4O2: C, 64.41; H,
d, Jꢁ8.6 Hz), 6.80—7.50 (7H, m). IR (KBr) n : 1707, 6.08; N, 18.78. Found: C, 64.67; H, 6.22; N, 18.61.
1666 cmꢂ1. Anal. Calcd for C24H26N4O3: C, 68.88; H, 6.26;
N, 13.39. Found: C, 68.62; H, 6.35; N, 13.54.
3,7-Dihydro-1-(4-methylbenzyl)-3-propyl-1H-purine-2,4-
dione (1f): Yield 60%. mp 175—176 °C. H-NMR (CDCl3)
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3,7-Dihydro-1-(3-methylbenzyl)-7-(4-methoxybenzyl)-3- d : 0.97 (3H, t, 3H, Jꢁ7.4 Hz), 1.70 (2H, sext., Jꢁ7.4 Hz),
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propyl-1H-purine-2,4-dione (4e): Yield 74%. Oil. H-NMR 2.30 (3H, s), 4.15 (2H, t, Jꢁ7.4 Hz), 5.22 (2H, s), 7.10 (2H,
(CDCl3) d: 0.97 (3H, t, 3H, Jꢁ7.5 Hz), 1.80 (2H, sext., d, Jꢁ9.0 Hz), 7.40 (2H, d, Jꢁ9.0 Hz), 7.70 (1H, s), 12.70
Jꢁ7.5 Hz), 2.27 (3H, s), 3.70 (3H, s), 4.05 (2H, t, Jꢁ7.5 Hz), (1H, br s). IR (KBr)n : 3425, 1707, 1664 cmꢂ1. Anal. Calcd
5.10 (2H, s), 5.33 (2H, s), 6.80 (2H, d, Jꢁ8.5 Hz), 6.90— for C16H18N4O2: C, 64.41; H, 6.08; N, 18.78. Found: C,
7.40 (7H, m), 7.47 (1H, s). IR (KBr)n : 1705, 1666 cmꢂ1. 64.64; H, 6.29; N, 18.79.
HR-MS m/z: 418.2010 (Calcd for 418.2005).
3,7-Dihydro-7-acetonyl-3-propyl-1H-purine-2,4-dione
3,7-Dihydro-1-(2-methylbenzyl)-7-(4-methoxybenzyl)-3- (6) A mixture of 3-propylxanthine (5, 0.97 g, 5.0 mmol),
propyl-1H-purine-2,4-dione (4f): Yield 72%. mp 105— acetonyl chloride (0.46 g, 5.0 mmol), and anhydrous K2CO3
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110 °C. H-NMR (CDCl3) d: 0.95 (3H, t, 3H, Jꢁ7.5 Hz), (0.71 g, 5.1 mmol) in DMF (10 ml) was heated at 60 °C for
1.69 (2H, sext., Jꢁ7.5 Hz), 2.31 (3H, s), 3.80 (3H, s), 4.03 2 h. The reaction mixture was poured into ice-water and neu-
(2H, t, Jꢁ7.5 Hz), 5.16 (2H, s), 5.45 (2H, s), 6.89 (2H, d, tralized with 2 N HCl. The resultant precipitate was filtered,
Jꢁ8.6 Hz), 6.96—7.40 (6H, m), 7.55 (1H, s). IR (KBr)n : and recrystallized from MeOH to give 6 (0.86 g, 67%). mp
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1707, 1666 cmꢂ1. Anal. Calcd for C24H26N4O3: C, 68.88; H, 231—232 °C. H-NMR (DMSO-d6) d : 0.67 (3H, t, Jꢁ7.2
6.26; N, 13.39. Found: C, 68.66; H, 6.34; N, 13.20.
Hz), 1.70 (2H, sext., Jꢁ7.2 Hz), 2.20 (3H, s), 3.90 (2H, t,
3,7-Dihydro-1-benzyl-3-propyl-1H-purine-2,4-dione (1) Jꢁ7.2 Hz), 5.45 (2H, s), 5.20 (2H, s), 7.90 (1H, s), 10.90
General Procedure: A mixture of 4 (2.0 mmol), conc. H2SO4 (1H, br s). IR (KBr)n : 3453, 1725, 1691 cmꢂ1. Anal. Calcd
(1 drop), and anisole (324 mg, 3.0 mmol) in trifluoroacetic for C11H14N4O3: C, 52.79; H, 5.64; N, 22.39. Found: C,
acid (4 ml) was refluxed for 9 h and then evaporated. The oily 52.81; H, 5.57; N, 22.51.
residue was diluted with water and adjusted to pH 6 by addi-
3,7-Dihydro-7-acetonyl-1-benzyl-3-propyl-1H-purine-
tion of 20% NaOH with stirring. The resultant precipitate 2,4-dione (2) General Procedure: A mixture of 6 (0.5 g,
was filtered, washed with water, and then isopropyl ether, 2.0 mmol), benzyl chloride (2.2 mmol), and anhydrous
dried, and recrystallized from benzene to afford 1.
K2CO3 (0.3 g, 2.2 mmol) in DMF (5.0 ml) was heated at
3,7-Dihydro-1-(2-chlorobenzyl)-3-propyl-1H-purine-2,4- 60 °C for 2 h. The reaction mixture was poured into ice-water
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dione (1a): Yield 67%. mp 230—231 °C. H-NMR (CDCl3) and neutralized with 2 N HCl. The mixture was extracted
d : 0.98 (3H, t, 3H, Jꢁ7.4 Hz), 1.70 (2H, sext., Jꢁ7.4 Hz), with CH2Cl2. The extract was dried and evaporated. The re-
4.10 (2H, t, Jꢁ7.4 Hz), 5.30 (2H, s), 6.90—7.20 (4H, m), sulting solid was recrystallized from CH2Cl2–diisopropyl
7.70 (1H, s), 13.00 (1H, br s). IR (KBr)n : 3425, 1705, ether to afford 2.
1664 cmꢂ1. Anal. Calcd for C15H15N4O2Cl: C, 56.52; H, 4.74;
N, 17.58. Found: C, 56.82; H, 4.67; N, 17.84.
3,7-Dihydro-7-acetonyl-1-(2-chlorobenzyl)-3-propyl-1H-
purine-2,4-dione (2a): Yield 92%. mp 191—192 °C. 1H-
3,7-Dihydro-1-(3-chlorobenzyl)-3-propyl-1H-purine-2,4- NMR (CDCl3) d : 0.97 (3H, t, 3H, Jꢁ7.2 Hz), 1.80 (2H,
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dione (1b): Yield 65%. mp 179—180 °C. H-NMR (CDCl3) sext., Jꢁ7.2 Hz), 2.30 (3H, s), 4.10 (2H, t, Jꢁ7.2 Hz), 5.15
d : 0.97 (3H, t, 3H, Jꢁ7.4 Hz), 1.70 (2H, sext., Jꢁ7.4 Hz), (2H, s), 5.30 (2H, s), 7.10—7.40 (4H, m), 7.55 (1H, s). IR
4.12 (2H, t, Jꢁ7.4 Hz), 5.30 (2H, s), 7.15—7.57 (4H, m), (KBr)n : 1731, 1689 cmꢂ1. Anal. Calcd for C18H19N4O3Cl: C,
7.87 (1H, s), 12.60 (1H, br s). IR (KBr)n : 3425, 1709, 57.68; H, 5.11; N, 14.95. Found: C, 57.75; H, 5.30; N, 14.84.
1660 cmꢂ1. Anal. Calcd for C15H15N4O2Cl: C, 56.52; H, 4.74;
N, 17.58. Found: C, 56.68; H, 4.61; N, 17.79.
3,7-Dihydro-7-acetonyl-1-(3-chlorobenzyl)-3-propyl-1H-
purine-2,4-dione (2b): Yield 90%. mp 119—120 °C. 1H-
3,7-Dihydro-1-(4-chlorobenzyl)-3-propyl-1H-purine-2,4- NMR (CDCl3) d : 0.97 (3H, t, 3H, Jꢁ7.2 Hz), 1.80 (2H,
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dione (1c): Yield 53%. mp 177—178 °C. H-NMR (CDCl3) sext., Jꢁ7.2 Hz), 2.30 (3H, s), 4.05 (2H, t, Jꢁ7.2 Hz), 5.15
d : 0.97 (3H, t, 3H, Jꢁ7.4 Hz), 1.70 (2H, sext., Jꢁ7.4 Hz), (4H, s), 7.15—7.45 (4H, m), 7.50 (1H, s). IR (KBr)n : 1730,
4.15 (2H, t, Jꢁ7.4 Hz), 5.20 (2H, s), 7.22 (2H, d, Jꢁ9.0 Hz), 1701, 1668 cmꢂ1. Anal. Calcd for C18H19N4O3Cl: C, 57.68;