Yi et al.
to flash chromatography (petroleum ether/AcOEt/CH2Cl2, 10:1:1)
to give 12 as a yellow powder (0.12 g, 63%): 1H NMR (CDCl3)
δ 12.12 (s, 1H), 10.29 (s, 1H), 8.57 (d, d, J1 ) 7.8 Hz, J2 ) 1.2
Hz, 1H), 8.44 (d, J ) 2.4 Hz, 1H), 8.11 (d, J ) 2.4 Hz, 1H), 7.12
(d, t, J1 ) 7.8 Hz, J2 ) 2.1 Hz, 1H), 7.03 (d, t, J1 ) 7.8 Hz, J2 )
2.1 Hz, 1H), 6.95 (d, d, J1 ) 8.1 Hz, J2 ) 1.2 Hz, 1H), 4.02 (s,
3H), 2.42 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 161.0, 156.9,
150.9, 141.4, 134.1, 130.9, 130.5, 128.4, 123.3, 122.4, 114.3, 33.8,
31.9, 29.7, 29.5, 29.4, 20.4, 14.1; MS (EI) m/z 302 [M]+; HRMS
(EI) calcd for C15H14N2O5, 302.3002; found, 302.2988. Anal. Calcd
for C15H14N2O5: C, 59.60; H, 4.67; N, 9.27. Found: C, 60.08; H,
4.97; N, 9.10.
TOF) m/z 435 [M + H]+; HRMS (MALDI-TOF) calcd for
C25H27N2O5 [M + H]+, 435.4844; found, 435.4880. Anal. Calcd
for C25H26N2O5: C, 69.11; H, 6.03; N, 6.45. Found: C, 69.16; H,
6.25; N, 6.43.
Compound 17 was prepared as a white solid (47%) from the
reaction of 7 and piperidine under similar conditions: 1H NMR
(CDCl3) δ 7.63 (d, J ) 1.8 Hz, 1H), 7.29 (d, J ) 1.8 Hz, 1H),
3.93 (s, 3H), 3.74 (d, J ) 22.5 Hz, 2H), 3.18 (d, J ) 23.4 Hz, 2H),
2.38 (s, 3H), 1.67-1.58 (m, 6H); 13C NMR (CDCl3) δ 165.5, 147.3,
143.6, 134.9, 133.7, 133.1, 125.8, 63.4, 48.2, 42.9, 29.7, 26.3, 25.6,
24.4, 20.5; MS (ESI) m/z 278 [M + H]+. Anal. Calcd for
C14H18N2O4: C, 60.42; H, 6.52; N, 10.07. Found: C, 60.11; H,
6.92; N, 9.81.
Compound 18 was prepared as a white solid (0.61 g, 60%) from
the reaction of 7 (0.68 g, 3.24 mmol) and 4-methoxyaniline (0.52
g, 4.22 mmol) according to the procedure described for the
preparation of 2: 1H NMR (300 MHz, CDCl3) δ 9.18 (s, 1H), 8.17
(d, J ) 1.8 Hz, 1H), 7.77 (d, J ) 1.8 Hz, 1H), 7.58 (d, d, J1 ) 1.8
Hz, J2 ) 9.0 Hz, 2H), 6.95 (d, d, J1 ) 1.8 Hz, J2 ) 9.3 Hz, 2H),
4.01 (s, 3H), 3.82 (s, 3H), 2.45 (s, 3H); 13C NMR (300 MHz,
CDCl3) δ 161.3, 156.9, 148.7, 144.1, 136.7, 135.6, 130.8, 129.3,
128.4, 121.9, 114.4, 64.2, 55.5, 20.7; MS (EI) m/z 316 [M]+. Anal.
Calcd for C16H16N2O5: C, 60.75; H, 5.10; N, 8.86. Found: C, 60.83;
H, 4.97; N, 8.66.
Compound 13. The reaction of 3 (0.13 g, 0.27 mmol) and
potassium hydroxide (0.90 g, 16.2 mmol) in refluxing water (40
mL) and dioxane (40 mL) for 10 h, after workup and column
chromatography (petroleum ether/AcOEt/CH2Cl2, 10:1:2), afforded
1
13 as a yellow solid (88 mg, 70%); H NMR (CDCl3) δ 12.26 (s,
1H), 10.34 (s, 1H), 10.12 (s, 1H), 8.59 (d, d, J1 ) 7.8 Hz, J2 ) 1.8
Hz, 1H), 8.55 (s, 1H), 8.51 (s, 1H), 8.18 (s, 1H), 7.74 (s, 1H),
7.14-6.95 (m, 2H), 6.96 (d, J ) 8.1 Hz, 1H), 3.99 (s, 3H), 3.95
(s, 3H), 2.46 (s, 3H), 2.43 (s, 3H), 2.420 (s, 3H); 13C NMR (CDCl3)
δ 162.7, 161.1, 150.8, 148.6, 145.5, 141.8, 135.3, 134.0, 131.6,
130.7, 128.8, 128.0, 127.1, 126.3, 125.4, 124.0, 123.4, 121.2, 120.7,
110.1, 29.7, 29.6, 21.4, 20.4; MS (ESI) m/z 465 [M]+.
Compound 14. The reaction of 4 (0.10 g, 0.16 mmol) and KOH
(0.54 g, 9.62 mmol) in dioxane (35 mL) and water (35 mL) was
refluxed for 10 h. After workup, the resulting residue was subjected
to column chromatography (petroleum ether/CH2Cl2/EtOAc, 6:1:
1) to afford 14 (37 mg, 37%) as a yellow solid: 1H NMR (CDCl3)
δ 12.34 (s, 1H), 10.40 (s, 1H), 10.04 (s, 2H), 8.59-8.55 (m, 3H),
8.52 (d, J ) 1.5 Hz, 1H), 8.19 (s, 1H), 7.72 (s, 1H), 7.69 (s, 1H),
7.14-7.01 (m, 2H), 6.95 (d, J ) 7.8 Hz, 1H), 4.07 (s, 3H), 4.00
(s, 3H), 3.96 (s, 3H), 2.54 (s, 3H), 2.46 (s, 3H), 2.37 (s, 3H); 13C
NMR (CDCl3) δ 163.2, 162.9, 161.2, 148.5, 145.5, 145.3, 141.9,
135.7, 135.4, 134.1, 131.9, 131.8, 130.9, 128.9, 128.0, 127.2, 127.0,
126.6, 126.5, 126.2, 125.8, 125.1, 124.0, 123.3, 121.3, 120.7, 110.2,
31.9, 29.7, 29.4, 29.2, 22.7, 14.1; MS (MALDI-TOF) m/z 628
[M]+; HRMS (EI) calcd for C33H33N4O9 [M + H]+, 629.2239;
found, 629.2242. Anal. Calcd for C33H32N4O9: C, 63.05; H, 5.13;
N, 8.91. Found: C, 62.96; H, 5.26; N, 8.70.
Compound 15. The solution of 5 (78 mg, 0.097 mmol) and
potassium hydroxide (0.32 g, 5.80 mmol) in dioxane (10 mL) and
water (10 mL) was heated under reflux for 24 h. After workup, the
crude product was purified by column chromatography (petroleum
ether/CH2Cl2/EtOAc, 5:1:1) to afford 15 (43 mg, 35%) as a yellow
solid: 1H NMR (CDCl3) δ 12.28 (s, 1H), 10.30 (s, 1H), 9.89 (s,
2H), 9.76 (s, 1H), 8.60 (d, J ) 1.5 Hz, 1H), 8.57 (d, J ) 1.5 Hz,
2H), 8.55 (s, 1H), 8.51 (d, J ) 2.1 Hz, 1H), 8.17 (d, J ) 1.8 Hz,
1H), 7.72 (d, J ) 2.1 Hz, 1H), 7.66 (s, 2H), 7.11-7.00 (m, 2H),
6.91 (d, J ) 8.1 Hz, 1H), 4.13 (s, 3H), 4.11 (s, 3H), 3.91 (s, 3H),
3.90 (s, 3H), 2.46 (s, 6H), 2.43 (s, 6H); 13C NMR (CDCl3) δ 163.5,
163.4, 163.0, 161.2, 150.8, 148.4, 145.6, 145.3, 141.9, 135.8, 135.7,
135.4, 131.9, 131.7, 131.7, 130.9, 128.9, 127.0, 126.6, 126.5, 126.2,
126.1, 125.7, 125.3, 124.0, 123.2, 121.4, 120.7, 110.2, 63.2, 62.9,
62.8, 55.9, 53.4, 31.9, 29.7, 29.3, 22.7, 21.4, 31.3, 20.4, 14.1; MS
(MALDI-TOF) m/z 791 [M]+; HRMS (MALDI-TOF) calcd for
C42H42N5O11 [M + H]+, 792.8097; found, 792.8080. Anal. Calcd
for C42H41N5O11: C, 63.71; H, 5.22; N, 8.84. Found: C, 63.38; H,
5.74; N, 8.59.
Compound 19 was prepared as an orange powder (26 mg, 57%)
from the reaction of 18 (60 mg, 0.19 mmol) and potassium
hydroxide (0.32 g, 5.69 mmol) in dioxane (40 mL) and water (10
mL) under similar conditions: 1H NMR (CDCl3) δ 12.18 (s, 1H),
9.59 (s, 1H), 8.46 (d, J ) 1.8 Hz, 1H), 8.11 (d, d, J1 ) 1.8 Hz, J2
) 1.2 Hz, 1H), 7.61 (s, 1H), 7.58 (s, 1H), 6.94 (s, 1H), 6.91 (s,
1H), 3.83 (s, 3H), 2.43 (s, 3H); 13C NMR (CDCl3) δ 161.0, 156.85,
150.9, 141.4, 134.1, 130.9, 130.5, 128.4, 123.3, 122.4, 114.3, 55.5,
29.5; MS (EI) m/z 302 [M]+; HRMS (EI) calcd for C15H15N2O5,
303.2900 [M + H]+; found, 303.2880. Anal. Calcd for C15H14N2O5:
C, 59.60; H, 4.67; N, 9.27. Found: C, 59.59; H, 4.54; N, 9.23.
Compounds 21a and 22a. A solution of 20a10a (0.23 g, 0.60
mmol) and lithium hydroxide hydrate (76 mg, 1.80 mmol) in
methanol (40 mL) and water (20 mL) was heated under reflux for
3 h and then cooled to room temperature. Dilute hydrochloric acid
was added to pH ) 4. The formed precipitate was filtered, washed
with cold water, dried in vacuo, and subjected to flash chroma-
tography (dichloromethane/methanol, 25:1) to give 21a (white solid,
0.19 g, 85%) and 22a (yellow solid, 26 mg, 12%). 21a: 1H NMR
(CDCl3) δ 10.27 (s, 1H), 8.67 (d, J ) 2.1 Hz, 1H), 8.25 (d, J )
2.4 Hz, 1H), 7.81 (d, J ) 2.4 Hz, 1H), 7.64 (d, J ) 2.1 Hz, 1H),
4.07 (s, 3H), 3.96 (s, 3H), 2.47 (s, 3H), 2.42 (s, 3H); 13C NMR
(CDCl3) δ 161.6, 149.2, 147.7, 144.0, 136.8, 135.4, 135.0, 132.3,
129.1, 128.5, 127.8, 126.7, 121.7, 64.4, 63.0, 29.7, 21.3, 20.7; MS
(EI) m/z 374 [M]+. Anal. Calcd for C18H18N2O7: C, 57.75; H, 4.85;
N, 7.48. Found: C, 57.90; H, 4.86; N, 7.93. 22a: 1H NMR (CDCl3)
δ 12.19 (s, 1H), 10.40 (s, 1H), 8.59 (s, 1H), 8.46 (s, 1H), 8.14 (s,
1H), 7.57 (s, 1H), 3.97 (s, 1H), 2.48 (s, 1H), 2.39 (s, 1H); 13C
NMR (CDCl3) δ 173.8, 166.7, 163.6, 137.7, 136.6, 136.4, 133.0,
131.7, 131.6, 129.0, 128.6, 126.7, 126.4, 121.8, 61.9, 20.6, 19.6;
MS (ESI) m/z 360 [M]+. Anal. Calcd for C17H16N2O7: C, 56.67;
H, 4.48; N, 7.77. Found: C, 56.34; H, 4.43; N, 7.56.
Compounds 21b and 22b were prepared from the reaction of
20b10a and lithium hydroxide according to the procedure for the
preparation of 21a and 22a. 21b (white solid): 1H NMR (CDCl3)
δ 10.25 (s, 1H), 10.20 (s, 1H), 8.75 (s, 1H), 8.62 (s, 1H), 8.26 (s,
1H), 7.84 (s, 1H), 7.73 (s, 1H), 7.62 (s, 1H), 4.09 (s, 3H), 3.98 (s,
3H), 3.96 (s, 3H), 2.49 (s, 3H), 2.46 (s, 3H), 2.43 (s, 3H); 13C
NMR (CDCl3) δ 163.1, 161.9, 149.1, 148.0, 147.4, 147.4, 145.3,
144.4, 136.9, 135.9, 135.5, 135.2, 132.6, 131.6, 129.1, 127.5, 127.1,
126.7, 126.7, 125.7, 125.4, 121.5, 74.1, 64.4, 63.3, 63.0, 62.9, 21.4,
21.3, 20.7, 15.3; MS (ESI) m/z 537 [M]+. Anal. Calcd for
C27H27N3O9: C, 60.33; H, 5.06; N, 7.82. Found: C, 60.88; H, 5.53;
N, 7.58. 22b (yellow solid): 1H NMR (300 MHz, CDCl3) δ 12.33
(d, J ) 3 Hz, 1H), 10.40 (s, 1H), 10.29 (s, 1H), 8.73 (d, J ) 2.1
Compound 16 was prepared as a white solid (71%) from the
reaction of 9 with 5-methyl-2-methoxybenzoyl chloride according
to the procedure described for the preparation of 2: 1H NMR
(CDCl3) δ 10.61 (s, 1H), 10.18 (s, 1H), 8.62-8.59 (m, 2H), 8.14
(d, J ) 2.4 Hz, 1H), 7.67 (d, J ) 2.1 Hz, 1H), 7.33 (d, d, J1 ) 4.5
Hz, J2 ) 8.4 Hz, 1H), 7.10-7.04 (m, 2H), 7.00-6.93 (m, 2H),
4.11 (s, 3H), 3.96 (s, 3H), 3.92 (s, 3H), 2.42 (s, 3H), 2.39 (s, 3H);
13C NMR (CDCl3) δ 163.4, 163.0, 155.3, 148.4, 145.3, 135.3, 133.9,
132.8, 132.4, 131.2, 128.2, 126.1, 125.3, 123.8, 121.3, 121.3, 120.6,
111.6, 110.1, 62.3, 56.1, 55.8, 29.7, 21.4, 20.4; MS (MALDI-
876 J. Org. Chem., Vol. 72, No. 3, 2007