172
Z. Wu et al.
13
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H6), C NMR (Z-isomer) 9.3 (C3 ), 14.7 (CH3), 18.8 (C4 ), 61.4 (CH2 of
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Et), 109.3, 116.7 (C1 , C2 ), 96.1, 140.5, 154.4, 166.1 (cytosine), 171.0 (C=O,
ester).
6-Benzyloxy-2-(dimethylaminomethyleneamino)purine
(10).
A
mixture of 2-amino-6-benzyloxypurine (9b, 5.6 g, 23 mmol) and
N,N-dimethylformamide dimethyl acetal (9.0 mL, 66.7 mmol) in DMF
(100 mL) was stirred at 40◦C for 16 hours. The solvent was evaporated in
vacuo and the crude product was crystallized from EtOAc (40 mL) to give
compound 10 (5.79 g, 85%) as a white solid, mp 244–245◦C. UV λmax 293
1
nm (ε 26,400), 233 (ε 14,200), 202 (ε 23,800). H NMR δ 2.99, 3.10 (2s,
6H, CH3), 5.54 (s, 2H, CH2 of Bn), 7.31–7.40 (m, 3H), 7.47 (d, 2H, J = 8.0
Hz, Ph), 8.01 (s, 1H, H8), 8.57 (s, 1H, N2=CH), 12.74 (bs, 1H, NH). 13C
NMR 35.2, 41.0 (CH3), 67.7 (CH2 of Bn), 128.6, 128.9, 129.1, 137.7 (Ph),
140.5, 142.9, 155.4, 158.6, 160.0, 162.3 (purine, N2=CH). EI-MS 296 (M,
5.2), 93 (100.0). HRMS calcd M 296.1386, found 296.1383. Anal. Calcd for
C15H16N6O: C, 60.80; H, 5.44; N, 28.36. Found: C, 60.81; H, 5.55; N, 28.20.
(Z)-6-Benzyloxy-2-formylamino-9-[(2-carbethoxycyclopropylidene)
methyl]purine (11) and (Z)-6-Benzyloxy-2-formylamino-7-[(2-carbethoxy-
cyclopropylidene)methyl]purine (13). A mixture of compound 10 (450
mg, 1.49 mmol), dichloro ester 2c (600 mg, 3.0 mmol) and K2CO3 (1.24
g, 8.93 mmol) in DMF (8 mL) was stirred at 110–115◦C under N2 for
40 hours. After cooling, the insoluble portion was filtered off and it
was washed with DMF. The filtrate was concentrated and residue was
chromatographed on a silica gel column using CH2Cl2-MeOH (100:1 to
20:1) to give the Z,N9-isomer 11 (239 mg, 41%), Z,N7-isomer Z-13 (20 mg,
3.4%) and mixture of the Z- and E-N7-isomer 13 (50 mg, 8.6%). In another
experiment run on a 4-mmol scale, compound 11 was obtained in 47%
yield.
Z,N9-Isomer 11: Mp 162–163◦C. UV λmax 271 (ε 18,000), 232 (ε 32,200),
210 nm (ε 32,800). 1H NMR δ 1.07 (t, J = 6.8 Hz, 3H, CH3), 1.92 (m, 1H),
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2.03 (t, 1H, J = 8.8 Hz, H3 ), 2.98 (m, 1H, H4 ), 4.02 (q, 2H, J = 6.8 Hz, CH2
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of Et), 5.59 (s, 2H, CH2 of Bn), 7.34–7.41, 7.49–7.53 (2m, 6H, Ph and H1 ),
8.29 (s, 1H, H8), 9.45 (d, J = 9.6 Hz, 1H, CH=O), 10.90 (d, J = 9.6 Hz,
1H, NH). 13C NMR 11.2 (C3 ), 14.6 (CH3), 20.2 (C4 ), 61.4 (CH2 of Et), 69.0
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(CH2 of Bn), 111.9, 114.5, 118.1, 140.1, 152.3, 153.5, 160.8 (C1 , C2 , purine),
129.0, 129.2, 129.4, 136.7 (Ph), 164.5 (CH=O), 170.8 (C=O, ester). EI-MS
393 (M, 15.6), 91 (100.0). HRMS calcd M 393.1437, found 393.1437. Anal.
Calcd for C20H19N5O4: C, 61.06; H, 4.87; N, 17.80. Found: C, 61.07; H, 4.76;
N, 17.79.
Z,N7-Isomer Z-13: Mp 153–154◦C. UV λmax 285 (ε 7,000), 250 (ε 33,300),
1
206 (ε 23,300). H NMR δ 1.10 (t, J = 6.4 Hz, 3H, CH3), 1.92–1.95 (m,
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1H), 2.01 (t, J = 8.8 Hz, 1H, H3 ), 2.94 (t, J = 5.6 Hz, 1H, H4 ), 4.04–4.07
(m, 2H, CH2 of Et), 5.62 (s, 2H, CH2 of Bn), 7.34–7.41 (m, 3H), 7.55 (d,