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dine-2,4(1H,3H)-dione (40) The same reaction and procedure using 33
(70.0 mg, 0.21 mmol) as described for the preparation of 35 gave a residue,
which was subjected to column chromatography (a gradient of 0—5%
MeOH in CHCl3) to afford compound 40 (40.4 mg, 63.5% yield) as a solid
(mp more than 300 °C). EI-MS: m/z 296 [M]ꢀ. HR-MS: m/z Calcd for
C16H12N2O4 [M]ꢀ; 296.0797, Found; 296.0790. 1H-NMR (DMSO-d6) d:
11.41 (1H, br s, H-3ꢄ), 8.01 (1H, d, Jꢅ7.9 Hz, H-5), 7.86 (1H, d, Jꢅ7.6 Hz,
H-6ꢄ), 7.84 (1H, d, Jꢅ1.8 Hz, H-8), 7.76 (1H, dd, Jꢅ7.9, 1.8 Hz, H-6), 6.98
(1H, q, Jꢅ1.5 Hz, H-3), 5.66 (1H, d, Jꢅ7.6 Hz, H-5ꢄ), 5.04 (2H, s, H-12),
2.11 (3H, d, Jꢅ1.5 Hz, H-11). 13C-NMR (DMSO-d6) d: 184.7 (C-1), 184.4
(C-4), 163.7 (C-4ꢄ), 151.0 (C-2ꢄ), 148.1 (C-2), 145.6 (C-7), 143.2 (C-6ꢄ),
135.2 (C-3), 132.7 (C-6), 131.9 (C-9), 131.1 (C-10), 126.7 (C-5), 124.2 (C-
8), 101.6 (C-5ꢄ), 50.2 (C-12), 15.9 (C-11).
5-Fluoro-1-[(7-methyl-5,8-dioxo-5,8-dihydronapphthalen-2-yl)-
methyl]pyrimidine-2,4(1H,3H)-dione (41) The same reaction and proce-
dure using 34 (80.0 mg, 0.23 mmol) as described for the preparation of 35
gave a residue, which was subjected to column chromatography (a gradient
of 0—5% MeOH in CHCl3) to afford compound 41 (41.0 mg, 56.1% yield)
as a solid (mp 155—157 °C). EI-MS: m/z 314 [M]ꢀ. HR-MS: m/z Calcd for
C16H11FN2O4 [M]ꢀ; 314.0703, Found; 314.0703. 1H-NMR (DMSO-d6) d:
11.92 (1H, br s, H-3ꢄ), 8.30 (1H, d, Jꢅ6.7 Hz, H-6ꢄ), 8.00 (1H, d, Jꢅ7.9 Hz,
H-5), 7.89 (1H, d, Jꢅ1.8 Hz, H-8), 7.79 (1H, dd, Jꢅ7.9, 1.8 Hz, H-6), 6.98
(1H, q, Jꢅ1.5 Hz, H-3), 4.98 (2H, s, H-12), 2.11 (3H, d, Jꢅ1.5 Hz, H-11).
13C-NMR (DMSO-d6) d: 184.6 (C-1), 184.4 (C-4), 157.5 (C-4ꢄ), 149.7 (C-
2ꢄ), 148.1 (C-2), 142.7 (C-7), 135.2 (C-5ꢄ), 132.8 (C-3), 132.7 (C-6), 131.9
(C-6), 131.1 (C-5), 130.1 (C-9), 129.9 (C-10), 126.6 (C-8), 124.4 (C-6ꢄ),
50.5 (C-12), 15.9 (C-11).
1-[(1,4-Dimethoxynaphthalen-2-yl)methyl]pyrrolidine (42) Pyrroli-
dine (91 ml, 1.1 mmol) was added to a solution of 19 (50 mg, 0.18 mmol) in
DMF (10 ml) and the mixture was then stirred at room temperature for
30 min. The reaction mixture was poured into ice-water (100 ml), neutralized
with 5% aqueous NaHCO3, and extracted with Et2O (50 mlꢃ3). The organic
extracts were washed with water, dried over MgSO4, and filtered. The filtrate
was evaporated to give a residue, which was subjected to column chromatog-
raphy (a gradient of 0—5% MeOH in toluene) to obtain compound 42
(31.2 mg, 64.7% yield). EI-MS: m/z 271 [M]ꢀ. HR-MS: m/z Calcd for
C17H21NO2 [M]ꢀ; 271.1572, Found; 271.1571. 1H-NMR (CDCl3) d: 8.20
(1H, d, Jꢅ8.2 Hz, H-5) 8.00 (1H, d, Jꢅ8.2 Hz, H-8), 7.52 (1H, ddd, Jꢅ8.2,
7.0, 1.2 Hz, H-6) or 7.46 (1H, ddd, Jꢅ8.2, 7.0, 1.2 Hz, H-7), 6.98 (1H, s, H-
3), 4.00 and 3.89 (each 3H, s, 1- or 4-OCH3), 3.88 (2H, s, H-11), 2.64 (4H,
s, –NCH2– ꢃ2) and 4.12 (4H, s, –NCH2– ꢃ2); 13C-NMR (CDCl3) d: 151.8
(C-4), 147.2 (C-1), 128.5 (C-9), 126.4 (C-10), 125.9 (C-7), 125.1 (C-6),
122.3 (C-5), 121.9 (C-8), 105.4 (C-2), 96.1 (C-3), 62.2 (1-OCH3), 55.8 (4-
OCH3), 54.3 (–NCH2CH2– ꢃ2), 54.1 (C-11), 23.6 (–NCH2CH2– ꢃ2).
1-[(1,4-Dimethoxynaphthalen-2-yl)methyl]-4-methylpiperazine (43)
The same reaction and preparation using 19 (100.0 mg, 0.36 mmol) and 1-
methylpiperazine (280 ml, 2.3 mmol) as described for the preparation of 42
gave compound 43 (57.0 mg, 51.4% yield). EI-MS: m/z 300 [M]ꢀ. HR-MS:
m/z Calcd for C18H24N2O2 [M]ꢀ; 300.1838, Found; 300.1829. 1H-NMR
(CDCl3) d: 8.21 (1H, d, Jꢅ8.2 Hz, H-5) 8.03 (1H, d, Jꢅ8.2 Hz, H-8), 7.50
(1H, ddd, Jꢅ8.2, 7.0, 1.2 Hz, H-6) or 7.43 (1H, ddd, Jꢅ8.2, 7.0, 1.2 Hz, H-
7), 6.90 (1H, s, H-3), 3.97 and 3.86 (each 3H, s, 1- or 4-OCH3), 3.34 (2H, s,
H-11), 2.50 (8H, m, NCH2ꢃ4) and 2.27 (3H, s, N–CH3). 13C-NMR (CDCl3)
d: 151.8 (C-4), 148.0 (C-1), 128.4 (C-9), 126.5 (C-10), 126.0 (C-7), 125.7
(C-6), 125.3 (C-5), 122.2 (C-8), 121.8 (C-2), 105.2 (C-3), 56.4 (1-OCH3),
55.7 (4-OCH3), 55.3 (–NCH2CH2ꢃ2), 53.2 (C-11), 46.1 (–NCH3).
Jꢅ6.7 Hz, H-6ꢄ), 8.04 (1H, d, Jꢅ1.8 Hz, H-8), 7.95 (1H, d, Jꢅ8.9 Hz, H-5),
7.60 (1H, dd, Jꢅ8.9, 1.8 Hz, H-6), 6.83 (1H, s, H-3), 4.98 (2H, s, 7-CH2-),
3.94 (3H, s, 4-OCH3), 3.76 (3H, s, 1-OCH3), 2.37 (3H, s, H-11). 13C-NMR
(DMSO-d6) d: 157.5 (C-4ꢄ), 157.3 (C-2ꢄ), 150.7 (C-4), 149.7 (C-1), 146.4
(C-5ꢄ), 132.8 (Cꢄ-6), 130.2 (C-7), 127.5 (C-9), 126.3 (C-6), 126.0 (C-2),
124.2 (C-10), 121.6 (C-5), 120.8 (C-8), 107.5 (C-3), 60.7 (OCH3), 55.6
(OCH3), 50.9 (7-CH2), 16.0 (C-11).
1-[(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)methyl]-5-methylpyrimi-
dine-2,4(1H,3H)-dione (35) To a solution of 28 (45.0 mg, 0.14 mmol) in
AcOH (5 ml), HNO3 (0.28 g, 2.90 mmol) was added, and the mixture was
stirred at room temperature for 1 h. The reaction mixture was poured into
ice-water (50 ml) and extracted with CHCl3 (50 mlꢃ3). The organic extracts
were neutralized with 5% aqueous NaHCO3, washed with water, dried over
MgSO4, and filtered. The filtrate was evaporated to give compound 35
(21.7 mg, 53.2% yield) as a solid (mp 206—207 °C). EI-MS: m/z 296 [M]ꢀ.
1
HR-MS: m/z Calcd for C16H12N2O4 [M]ꢀ; 296.0797, Found; 296.0792. H-
NMR (CDCl3) d: 9.05 (1H, br s, H-3ꢄ), 8.09 (2H, m, H-5 and 8), 7.78 (2H,
m, H-6 and 7), 7.24 (1H, q, Jꢅ1.2 Hz, H-6ꢄ), 6.94 (1H, t, Jꢅ1.2 Hz, H-3),
4.80 (2H, d, Jꢅ1.2 Hz, H-11), 1.95 (3H, d, Jꢅ1.2 Hz, 5ꢄ-CH3). 13C-NMR
(CDCl3) d: 184.8 (C-1), 184.4 (C-4), 163.9 (C-4ꢄ), 150.7 (C-2ꢄ), 143.1 (C-
2), 140.5 (C-6ꢄ), 136.8 (C-3), 134.4 (C-7), 134.1 (C-6), 132.0 (C-9), 131.7
(C-10), 126.6 (C-8), 126.5 (C-5), 111.5 (C-5ꢄ), 46.7 (C-11), 12.4 (5ꢄ-CH3).
1-[(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)methyl]pyrimidine-
2,4(1H,3H)-dione (36) The same reaction and preparation using 29
(700 mg, 0.22 mmol) as described for the preparation of 35 gave compound
36 (302.4 mg, 47.8%yield) as solid (mp 236—237 °C). EI-MS: m/z 282
[M]ꢀ. HR-MS: m/z Calcd for C15H10N2O4 [M]ꢀ; 282.0641, Found;
282.0643. 1H-NMR (DMSO-d6) d: 11.37 (1H, br s, H-3ꢄ), 8.04 and 7.99
(each 1H, m, H-5 or 8), 7.90 (2H, m, H-6 and 7), 7.67 (1H, d, Jꢅ7.9 Hz, H-
6ꢄ), 6.70 (1H, t, Jꢅ1.5 Hz, H-3), 5.65 (1H, d, Jꢅ7.9 Hz, H-5ꢄ), 4.81 (2H, d,
Jꢅ1.5 Hz, H-11). 13C-NMR (DMSO-d6) d: 184.3 (C-1), 184.0 (C-4), 163.7
(C-4ꢄ), 150.9 (C-2ꢄ), 145.6 (C-2), 145.0 (C-6ꢄ), 134.4 (C-7), 134.3 (C-6),
134.0 (C-3), 131.6 (C-9), 131.5 (C-10), 126.1 (C-8), 125.8 (C-5), 101.6 (C-
5ꢄ), 46.0 (C-11).
1-[(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)methyl]-5-fluoropyrimi-
dine-2,4(1H,3H)-dione (37) The same reaction and procedure using 30
(80.0 mg, 0.24 mmol) as described for the preparation of 35 gave compound
37 (37.6 mg, 51.7% yield) as solid (mp 90—92 °C). EI-MS: m/z 300 [M]ꢀ.
1
HR-MS: m/z Calcd for C15H9FN2O4 [M]ꢀ; 300.0546, Found; 300.0543. H-
NMR (DMSO-d6) d: 11.87 (1H, br s, H-3ꢄ), 8.05 and 8.00 (each 1H, m, H-5
or 8), 8.04 (1H, d, Jꢅ6.7 Hz, H-6ꢄ), 7.90 (2H, m, H-6 and 7), 6.89 (1H, t,
Jꢅ1.5 Hz, H-3), 4.77 (2H, d, Jꢅ1.5 Hz, H-11). 13C-NMR (DMSO-d6) d:
184.4 (C-1), 184.1 (C-4), 157.7 (C-4ꢄ), 1489.7 (C-2ꢄ), 144.6 (C-2), 139.1
(C-5ꢄ), 134.4 (C-3), 134.3 (C-7), 134.2 (C-6), 131.6 (C-6ꢄ), 130.0 (C-10),
129.8 (C-9), 126.1 (C-8), 125.8 (C-5), 46.3 (C-11).
7-[(6-Amino-9H-purin-9-yl)methyl]-2-methylnaphthalene-1,4-dione
(38) The same reaction and procedure using 31 (100 mg, 0.29 mmol) as
described for the preparation of 35 gave a residue, which was subjected to
column chromatography (a gradient of 0—5% MeOH in toluene) to afford
compound 38 (20.0 mg, 21.9% yield) as a pale yellowish solid (mp 134—
135 °C). EI-MS: m/z 319 [M]ꢀ. HR-MS: m/z Calcd for C17H13N5O2 [M]ꢀ;
319.1069, Found; 319.1064. 1H-NMR (DMSO-d6) d: 8.33 (1H, s, H-8ꢄ),
8.14 (1H, s, H-2ꢄ), 7.98 (1H, d, Jꢅ8.2 Hz, H-5), 7.83 (1H, d, Jꢅ1.8 Hz, H-
8), 7.74 (1H, dd, Jꢅ8.2, 1.8 Hz, H-6), 7.30 (2H, br s, 6ꢄ-NH2), 6.95 (1H, q,
Jꢅ1.2 Hz, H-3), 5.53 (2H, s, H-12), 2.09 (3H, d, Jꢅ1.2 Hz, H-11). 13C-NMR
(DMSO-d6) d: 184.5 (C-1) , 184.2 (C-4), 156.0 (C-6ꢄ), 152.7 (C-2ꢄ), 149.4
(C-4ꢄ), 148.0 (C-8ꢄ), 143.2 (C-7), 135.1 (C-9), 133.2 (C-3), 132.6 (C-6),
131.9 (C-10), 131.0 (C-2), 126.6 (C-5), 124.2 (C-8), 118.6 (C-5ꢄ), 45.7 (C-
12), 15.8 (C-11).
5-Methyl-1-[(7-methyl-5,8-dioxo-5,8-dihydronaphthalen-2-
yl)methyl]pyrimidine-2,4(1H,3H)-dione (39) The same reaction and pro-
cedure using 32 (65.0 mg, 0.19 mmol) as described for the preparation of 35
gave a residue, which was subjected to column chromatography (a gradient
of 0—3% MeOH in CHCl3) to give compound 39 (38.0 mg, 64.1% yield) as
a solid (mp 267 —269 °C). EI-MS: m/z 310 [M]ꢀ. HR-MS: m/z Calcd for
C17H14N2O4 [M]ꢀ; 310.0954, Found; 310.0953. 1H-NMR (DMSO-d6) d:
11.41 (1H, br s, H-3ꢄ), 8.00 (1H, d, Jꢅ8.2 Hz, H-5), 7.85 (1H, d, Jꢅ1.8 Hz,
H-8), 7.73 (1H, dd, Jꢅ8.2, 1.8 Hz, H-6), 7.71 (1H, q, Jꢅ1.2 Hz, H-6ꢄ), 6.97
(1H, q, Jꢅ1.53 Hz, H-3), 5.00 (2H, s, H-12), 2.11 (3H, d, Jꢅ1.5 Hz, H-11),
1.73 (3H, d, Jꢅ1.2 Hz, 5ꢄ-CH3). 13C-NMR (DMSO-d6) d: 184.6 (C-1), 184.3
(C-4), 164.1 (C-4ꢄ), 150.9 (C-2ꢄ), 148.0 (C-2), 143.2 (C-7), 141.2 (C-6ꢄ),
135.1 (C-3), 132.6 (C-6), 131.9 (C-9), 130.1 (C-10), 126.6 (C-5), 124.2 (C-
8), 109.2 (C-5ꢄ), 49.9 (C-12), 15.8 (C-11), 11.9 (5ꢄ-CH3).
4-[(1,4-Dimethoxynaphthalen-2-yl)methyl]morpholine (44) The
same reaction and procedure fusing 19 (100.0 mg, 0.36 mmol) and 1-
methylpiperazine (217 ml, 2.5 mmol) as described for the preparation of 42
gave compound 44 (64.0 mg, 62.6% yield) as a solid (mp 56—58 °C). EI-
MS: m/z 287 [M]ꢀ. HR-MS: m/z Calcd for C18H24N2O2 [M]ꢀ; 287.1521,
1
Found; 287.1526. H-NMR (CDCl3) d: 8.22 (1H, d, Jꢅ8.2 Hz, H-5) 8.04
(1H, d, Jꢅ8.2 Hz, H-8), 7.52 (1H, ddd, Jꢅ8.2, 7.0, 1.2 Hz, H-6) or 7.46 (1H,
ddd, Jꢅ8.2, 7.0, 1.2 Hz, H-7), 6.91 (1H, s, H-3) 3.99 and 3.89 (each 3H, s,
1- or 4-OCH3), 3.71 (2H, s, H-11), 3.72 (4H, s, –NCH2ꢃ2) and 2.53 (4H, m,
–CH2OCH2–). 13C-NMR (CDCl3) d: 151.8 (C-4), 148.0 (C-1), 128.4 (C-9),
126.5 (C-10), 126.0 (C-7), 125.7 (C-6), 125.3 (C-5), 122.2 (C-8), 121.8 (C-
2), 105.2 (C-3), 67.1 (–CH2OCH2–), 62.4 (1-OCH3), 56.8 (4-OCH3), 55.7
(–NCH2ꢃ2), 53.7 (C-11).
1-[(1,4-Dimethoxynaphthalen-2-yl)methyl]-1H-imidazole (45) The
same reaction and procedure using 19 (100.0 mg, 0.36 mmol) and imidazol
(120 mg, 1.78 mmol) as described for the preparation of 42 gave compound
45 (44.6 mg, 46.7% yield) as a solid (mp 88—90 °C). EI-MS: m/z 268 [M]ꢀ.
1
HR-MS: m/z Calcd for C16H16N2O2 [M]ꢀ; 268.1212, Found; 268.1220. H-
1-[(7-Methyl-5,8-dioxo-5,8-dihydronaphthalen-2-yl)methyl]pyrimi-