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L. Hu et al. / Bioorg. Med. Chem. 20 (2012) 177–182
6.1. General procedure for the synthesis of 1,3-diketo
derivatives 5
6.87–7.05 (m, 3H, Ar-H), 7.30–7.32 (m, 1H, Ar-H), 7.33 (s, 1H, –
COCH–), 7.45–7.55 (m, 3H, Ar-H), 7.99–8.01 (m, 2H, Ar-H); 13C
NMR (CDCl3, 100 MHz, d ppm) 9.4, 51.2, 94.4, 114.2, 114.5, 115.6,
115.9, 122.8, 127.1, 128.7, 130.9, 132.3, 134.5, 136.8, 142.2,
181.1, 184.2; HRMS: m/z calcd for C19H17FN3O2: 338.1299; found:
338.1304; calcd for C19H16FN3NaO2: 360.1118; found: 360.1123;
HPLC purity 98.83%.
To a suspension of sodium hydride (60% dispersion in oil)
(20 mmol) in dry tetrahydrofuran (10 mL) was slowly added 1,2,3-
triazoles 3 (10 mmol) in dry THF (10 mL) at 0 °Cand the mixture
was stirred for 5 min. After that, variable methoxy substituted ethyl
benzoate 4 (15 mmol) in dry THF (15 mL) was added to the above
solution at 0 °Cand then the reaction mixture was slowly heated to
refluxing for about 90 min with stirring till TLC confirmed that the
reaction had finished. And then the cooled mixture was poured into
a mixture of ice-water (20 mL) and concentrated HCl (5 mL), ex-
tracted with EtOAc and purified by flash chromatography on silica
gel eluting with petroleum ether/ethyl acetate (4:1).
6.1.6. (Z)-1-(1-(3-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-(4-methoxyphenyl)prop-2-en-1-one (5f)
White powder; yield 63%; mp 127–128 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.57 (s, 3H, triazole-CH3), 3.89 (s, 3H, Ar-OCH3),
5.55 (s, 2H, Ar-CH2–), 6.91–6.96 (m, 2H, Ar-H), 6.98 (d, 2H,
J = 8.8 Hz, Ar-H), 7.02–7.07 (m, 1H, Ar-H), 7.28 (s, 1H, –COCH–),
7.32–7.38 (m, 2H, Ar-H), 8.02 (d, 2H, J = 9.2 Hz, Ar-H); 13C NMR
(CDCl3, 100 MHz, d ppm) 9.3, 51.1, 55.5, 93.3, 113.9, 114.2, 115.8,
122.7, 127.0, 129.2, 130.9, 136.5, 142.0, 163.2, 182.0, 182.5; HRMS:
m/z calcd for C20H19FN3O3: 368.1410; found: 368.1405; HPLC pur-
ity 100%.
6.1.1. (Z)-1-(1-(4-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-phenylprop-2-en-1-one (5a)
White powder; yield 67%; mp 128–130 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.56 (s, 3H, triazole-CH3), 5.51 (s, 2H, Ar-CH2–),
7.07 (t, 2H, J = 8.4 Hz, Ar-H), 7.18–7.21 (m, 2H, Ar-H), 7.33 (s, 1H,
–COCH–), 7.45–7.55 (m, 3H, Ar-H), 8.01 (t, 2H, J = 6.4 Hz, Ar-H);
13C NMR (CDCl3, 100 MHz, d ppm) 9.4, 51.0, 94.5, 116.3, 116.6,
127.0, 129.1, 129.2, 129.9, 132.3, 134.5, 136.6, 142.1, 181.0,
6.1.7. (Z)-3-(3,4-Dimethoxyphenyl)-1-(1-(3-fluorobenzyl)-5-
methyl-1H-1,2,3-triazol-4-yl)-3-hydroxyprop-2-en-1-one (5g)
White powder; yield 61%; mp 122–124 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.57 (s, 3H, triazole-CH3), 3.97 (s, 3H, Ar-OCH3),
3.99 (s, 3H, Ar-OCH3), 5.55 (s, 2H, Ar-CH2–), 6.89–6.92 (m, 1H, Ar-
H), 6.98 (t, 2H, J = 8.4 Hz, Ar-H), 7.02–7.07 (m, 1H, Ar-H), 7.28 (s,
1H, –COCH–), 7.32–7.38 (m, 1H, Ar-H), 7.55 (d, 1H, J = 2.0 Hz, Ar-
H), 7.70 (dd, 1H, J = 2.0 and 8.4 Hz, Ar-H); 13C NMR (CDCl3,
100 MHz, d ppm) 9.3, 51.1, 56.1, 77.3, 93.5, 109.7, 110.1, 110.6,
114.2, 115.8, 121.4, 122.9, 127.4, 130.8, 136.5, 141.9, 149.1,
152.7, 181.9, 182.5; HRMS: m/z calcd for C21H21FN3O4: 398.1516;
found: 398.1514; HPLC purity 99.54%.
184.3; HRMS: m/z calcd for
C19H17FN3O2: 338.1299; found:
338.1304; calcd for C19H16FN3NaO2: 360.1118; found: 360.1122;
HPLC purity 99.26%.
6.1.2. (Z)-1-(1-(4-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-(4-methoxyphenyl)prop-2-en-1-one (5b)
White powder; yield 56%; mp 145–146 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.55 (s, 3H, triazole-CH3), 3.88 (s, 3H, Ar-OCH3),
5.51 (s, 2H, Ar-CH2–), 6.96 (d, 2H, J = 9.6 Hz, Ar-H), 7.06 (t, 2H,
J = 6.4 Hz, Ar-H), 7.17–7.21 (m, 2H, Ar-H), 7.25 (s, 1H, –COCH–),
7.99 (d, 2H, J = 6.4 Hz, Ar-H); 13C NMR (CDCl3, 100 MHz, d ppm)
9.3, 51.0, 55.5, 93.3, 113.9, 116.3, 129.3, 129.9, 131.0, 136.3,
142.0, 163.2, 181.9, 182.6; HRMS: m/z calcd for C20H19FN3O3:
368.1410; found: 368.1408; HPLC purity 98.99%.
6.1.8. (Z)-1-(1-(3-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (5h)
White powder; yield 72%; mp 112–113 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.57 (s, 3H, triazole-CH3), 3.94 (s, 3H, Ar-OCH3),
3.96 (s, 6H, Ar-OCH3), 5.55 (s, 2H, Ar-CH2–), 6.89–7.07 (m, 3H, Ar-
H), 7.25 (s, 2H, Ar-H), 7.28(s, 1H, –COCH–), 7.31–7.38 (m, 1H, Ar-
H); 13C NMR (CDCl3, 100 MHz, d ppm) 9.3, 51.1, 56.3, 61.0, 93.9,
104.4, 114.2, 114.4, 115.6, 115.8, 122.7, 129.8, 130.9, 136.7,
141.9, 153.2, 164.3, 181.8, 182.9; HRMS: m/z calcd for
6.1.3. (Z)-3-(3,4-Dimethoxyphenyl)-1-(1-(4-fluorobenzyl)-5-
methyl-1H-1,2,3-triazol-4-yl)-3-hydroxyprop-2-en-1-one (5c)
White powder; yield 60%; mp 141–142 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.56 (s, 3H, triazole-CH3), 3.96 (s, 3H, Ar-OCH3),
3.98 (s, 3H, Ar-OCH3), 5.51 (s, 2H, Ar-CH2–), 6.94 (d, 1H,
J = 8.8 Hz, Ar-H), 7.07 (t, 2H, J = 6.4 Hz, Ar-H), 7.17–7.21 (m, 2H,
Ar-H), 7.27 (s, 1H, –COCH–), 7.53 (d, 1H, J = 2.0 Hz, Ar-H), 7.68
(dd, 1H, J = 2.0 and 8.4 Hz, Ar-H); 13C NMR (CDCl3, 100 MHz, d
ppm) 9.4, 51.0, 56.0, 93.4, 109.5, 110.1, 110.6, 116.3, 121.4,
129.1, 129.3, 129.9, 136.3, 141.9, 149.0, 152.8, 161.5, 181.9,
C22H23FN3O5: 428.1622; found: 428.1619; HPLC purity 99.76%.
6.2. General procedure for the synthesis of 1,3-diketo
derivatives 6
To a suspension of 1,3-diketo derivatives 6 with methyloxy
groups (5 mmol) in dry CH2Cl2 (20 mL) was added 1 N tribromobo-
rane solution (15 mL) at 0 °C and the mixture was stirred overnight
at room tempreture. After that, water (15 mL) was slowly added to
the above solution at 0 °C with stirring, followed by evaporation of
the sovent under reduced pressure, extracted with EtOAc and puri-
fied by flash chromategraphy on silica gel eluting with petroleum
ether/ethyl acetate (1:1).
182.5; HRMS: m/z calcd for
C21H21FN3O4: 398.1516; found:
398.1513; HPLC purity 98.45%.
6.1.4. (Z)-1-(1-(4-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (5d)
White powder; yield 52%; mp 156–158 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.57 (s, 3H, triazole-CH3), 3.94 (s, 3H, Ar-OCH3),
3.96 (s, 6H, Ar-OCH3), 5.52 (s, 2H, Ar-CH2-), 7.08 (t, 2H, J = 8.4 Hz,
Ar-H), 7.19–7.22 (m, 2H, Ar-H), 7.24 (s, 2H, Ar-H), 7.25 (s, 1H, –
COCH–); 13C NMR (CDCl3, 100 MHz, d ppm) 9.3, 51.1, 56.4, 60.9,
93.9, 104.6, 116.0, 116.3, 129.0, 129.2, 129.9, 136.4, 141.8, 153.1,
161.5, 181.7, 182.8; HRMS: m/z calcd for C22H23FN3O5: 428.1622;
found: 428.1619; HPLC purity 98.89%.
6.2.1. (Z)-1-(1-(4-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-(4-hydroxyphenyl)prop-2-en-1-one (6a)
Yellow powder; yield 78%; mp 208–210 °C; 1H NMR (DMSO-d6,
400 MHz, d ppm) 2.58 (s, 3H, triazole-CH3), 5.67 (s, 2H, Ar-CH2–),
6.93 (d, 2H, J = 9.6 Hz, Ar-H), 7.13 (s, 1H, –COCH–), 7.24 (t, 2H,
J = 6.4 Hz, Ar-H), 7.29–7.33 (m, 2H, Ar-H), 7.91 (d, 2H, J = 6.4 Hz,
Ar-H), 10.41 (s, 1H, Ar-OH); 13C NMR (DMSO-d6, 100 MHz, d
ppm) 9.4, 50.3, 92.6, 115.8, 116.1, 116.3, 124.8, 129.7, 130.2,
131.5, 137.4, 141.0, 161.0, 182.1, 182.7; HRMS: m/z calcd for
6.1.5. (Z)-1-(1-(3-Fluorobenzyl)-5-methyl-1H-1,2,3-triazol-4-
yl)-3-hydroxy-3-phenyl-prop-2-en-1-one (5e)
White powder; yield 75%; mp 105–107 °C; 1H NMR (CDCl3,
400 MHz, d ppm) 2.56 (s, 3H, triazole-CH3), 5.53 (s, 2H, Ar-CH2–),