JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
1353
Table 3. Reaction scheme.
(m, 3H, Ar), 7.37 (m, 1H, Ar), 7.16 (t, 1H, Ar), 7.11 (d, J ¼ 7.2 Hz, 1H,
Ar), 7.04 (s, 1H, Ar), 2.62 (s, 3H, CH3). 13 C NMR (150 MHz, CDCl3) d
155.51 (s), 153.89 (s), 130.67 (s), 128.69 (d, J ¼ 11.6 Hz), 128.40 (s),
125.19 (s), 124.87 (s), 122.94 (s), 121.40 (s), 118.33 (s), 101.56 (s),
15.04 (s). MS: m/z (%) [M þ H]þ 209.6, [M þ Na]þ 231.1.
Negative
control
Positive
control
Assay description
Inhibition
Fluorescent assay buffer
BACE1 substrate solution, 50 mM
BACE1 enzyme solution, 0.3 unit/mL
Inhibitor solution
80 mL
20 mL
–
78 mL
20 mL
2 mL
78-X mL
20 mL
2 mL
–
–
X mL
Total
100 mL
100 mL
100 mL
3.2.5.8. 6-Methyl-2-phenylbenzofuran (8). White solid, yield
85.32%. 1H NMR (600 MHz, CDCl3) d 7.87 (dd, J ¼ 8.4, 1.2 Hz, 2H,
Ar), 7.46 (m, 3H, Ar), 7.36 (m, 2H, Ar), 7.08 (dd, J ¼ 7.9, 0.7 Hz, 1H,
Ar), 7.00 (d, J ¼ 0.8 Hz, 1H, Ar), 2.51 (s, 3H, CH3). 13 C NMR
(150 MHz, CDCl3) d 155.33 (s), 155.31 (s), 134.54 (s), 130.67 (s),
128.73 (s), 128.25 (s), 126.67 (s), 124.73 (s), 124.33 (s), 120.34 (s),
111.41 (s), 101.16 (s), 21.74 (s). MS: m/z (%) [M þ Na]þ 231.6.
1
3.2.5.1. 2-Phenylbenzofuran (1). White solid, yield 65.14%. H NMR
(600 MHz, CDCl3) d 7.90 (m, 2H, Ar), 7.61 (d, J ¼ 7.6 Hz, 1H, Ar),
7.55 (d, J ¼ 8.1 Hz, 1H, Ar), 7.47 (t, 2H, Ar), 7.38 (t, 1H, Ar), 7.31 (dd,
1H, Ar), 7.25 (d, J ¼ 7.3 Hz, 1H, Ar), 7.05 (s, 1H, Ar). 13 C NMR
(150 MHz, CDCl3) d 155.90 (s), 154.87 (s), 130.47 (s), 129.20 (s),
128.77 (s), 128.53 (s), 124.92 (s), 124.24 (s), 122.91 (s), 120.88 (s),
111.16 (s), 101.28 (s). MS: m/z (%) [M þ Na]þ 217.6.
3.2.5.9. 5-Methyl-2-phenylbenzofuran (9). White solid, yield
1
91.11%. H NMR (600 MHz, CDCl3) d 7.88 (m, 2H, Ar), 7.44 (dd, 3H,
Ar), 7.37 (dd, 2H, Ar), 7.12 (dd, J ¼ 8.3, 1.3 Hz, 1H, Ar), 6.97 (s, 1H,
Ar), 2.47 (s, 3H, CH3). 13 C NMR (150 MHz, CDCl3) d 155.97 (s),
153.31 (s), 132.31 (s), 130.61 (s), 129.29 (s), 128.73 (s), 128.39 (s),
125.51 (s), 124.83 (s), 120.71 (s), 110.63 (s), 101.06 (s), 21.33 (s). MS:
m/z (%) [M þ H]þ 209.1, [M þ Na]þ 231.1.
3.2.5.2. 7-Methoxy-2-phenylbenzofuran (2). White solid, yield
90.91%. 1H NMR (600 MHz, CDCl3) d 7.92 (m, 2H, Ar), 7.46 (t, 2H,
Ar), 7.36 (t, 1H, Ar), 7.19 (m, 2H, Ar), 7.03 (s, 1H, Ar), 6.83 (d,
J ¼ 7.7 Hz, 1H, Ar), 4.07 (s, 3H, OCH3). 13 C NMR (150 MHz, CDCl3) d
156.05 (s), 145.31 (s), 144.11 (s), 130.91 (s), 130.31 (s), 128.69 (s),
128.53 (s), 125.02 (s), 123.57 (s), 113.31 (s), 106.69 (s), 101.61 (s),
56.13 (s). MS: m/z (%) [M þ Na]þ 247.5, [2M þ Na]þ 471.5.
3.2.5.10. 4,7-Dimethyl-2-phenylbenzofuran (10). White solid, yield
1
58.0%. H NMR (600 MHz, CDCl3) d 7.92 (dd, J ¼ 8.3, 1.1 Hz, 2H, Ar),
7.48 (t, 2H, Ar), 7.37 (m, 1H, Ar), 7.06 (s, 1H, Ar), 7.01 (d, J ¼ 7.4 Hz,
1H, Ar), 6.96 (d, J ¼ 7.4 Hz, 1H, Ar), 2.58 (s, 3H, CH3), 2.54 (s, 3H,
CH3). 13 C NMR (150 MHz, CDCl3) d 155.02 (s), 153.60 (s), 130.80 (s),
128.71 (s), 128.43 (s), 128.25 (s), 128.08 (s), 125.07 (s), 124.79 (s),
123.10 (s), 118.58 (s), 100.29 (s), 18.34 (s), 14.81 (s). MS: m/z (%)
[M þ H]þ 223.2, [M þ Na]þ 245.3, [2M þ Na]þ 467.3.
3.2.5.3. 6-Methoxy-2-phenylbenzofuran (3). White solid, yield
79.4%. 1H NMR (600 MHz, CDCl3) d 7.83 (m, 2H, Ar), 7.45 (m, 3H,
Ar), 7.34 (t, 1H, Ar), 7.09 (d, J ¼ 1.8 Hz, 1H, Ar), 6.97 (s, 1H, Ar), 6.89
(dd, J ¼ 8.5, 2.2 Hz, 1H, Ar), 3.89 (s, 3H, OCH3). 13 C NMR (150 MHz,
CDCl3) d 158.05 (s), 155.89 (s), 155.12 (s), 130.69 (s), 128.73 (s),
128.03 (s), 124.43 (s), 122.53 (s), 120.97 (s), 111.95 (s), 101.13 (s),
95.85 (s), 55.72 (s). MS: m/z (%) [M þ Na]þ 247.2, [2M þ Na]þ 471.2.
3.2.5.11. 2-Phenylnaphtho[2,1-b]furan (11). White solid, yield
1
81.8%. H NMR (600 MHz, CDCl3) d 8.08 (d, J ¼ 8.2 Hz, 1H, Ar), 7.85
3.2.5.4. 5-Methoxy-2-phenylbenzofuran (4). White solid, yield
83.3%. 1H NMR (600 MHz, CDCl3) d 7.86 (m, 2H, Ar), 7.44 (dd, 3H,
Ar), 7.36 (t, 1H, Ar), 7.06 (d, J ¼ 2.6 Hz, 1H, Ar), 6.98 (s, 1H, Ar), 6.91
(dd, J ¼ 8.9, 2.6 Hz, 1H, Ar), 3.88 (s, 3H, OCH3). 13 C NMR (150 MHz,
CDCl3) d 156.68 (s), 156.05 (s), 149.92 (s), 130.53 (s), 129.75 (s),
128.75 (s), 128.48 (s), 124.83 (s), 112.96 (s), 111.58 (s), 103.29 (s),
101.45 (s), 55.88 (s). MS: m/z (%) [M þ Na]þ 247.6,
[2M þ Na]þ 471.6.
(m, 3H, Ar), 7.62 (m, 2H, Ar), 7.51 (m, 1H, Ar), 7.41 (m, 4H, Ar), 7.16
(s, 1H, Ar). 13 C NMR (150 MHz, CDCl3) d 155.37 (s), 152.35 (s),
130.63 (s), 130.41 (s), 128.83–128.79 (d, J ¼ 6.1 Hz), 128.25 (s),
127.59(s), 126.25 (s), 125.16 (s), 124.64 (s), 124.55–124.52 (d
J ¼ 4.5 Hz), 123.44 (s), 112.27 (s), 100.43 (s). MS: m/z (%) [M þ H]þ
245.6, [M þ Na]þ 267.5.
3.2.5.12. 2-Phenylnaphtho[1,2-b]furan (12). White solid, yield
1
83.2%. H NMR (600 MHz, CDCl3) d 8.43 (d, J ¼ 8.2 Hz, 1H, Ar), 7.97
3.2.5.5. 4-Methoxy-2-phenylbenzofuran (5). White solid, yield
(m, 3H, Ar), 7.64 (m, 3H, Ar), 7.51 (m, 3H, Ar), 7.38 (m, 1H, Ar), 7.17
(s, 1H, Ar). 13 C NMR (150 MHz, CDCl3) d 155.30 (s), 150.29 (s),
131.47 (s), 130.72 (s), 128.81 (s), 128.41 (s), 128.21 (s), 126.33 (s),
125.02 (s), 124.80 (s), 124.65 (s), 123.61 (s), 121.33 (s), 120.01 (s),
119.54 (s), 102.45 (s). MS: m/z (%) [M þ H]þ 245.3, [M þ Na]þ 267.1.
1
71.6%. H NMR (600 MHz, CDCl3) d 7.87 (dd, J ¼ 8.3, 1.2 Hz, 2H, Ar),
7.46 (t, 2H, Ar), 7.35 (t, 1H, Ar), 7.23 (t, 1H, Ar), 7.19 (d, J ¼ 8.3 Hz,
1H, Ar), 7.15 (d, J ¼ 0.7 Hz, 1H, Ar), 6.69 (d, J ¼ 7.8 Hz, 1H, Ar), 3.98
(s, 3H, OCH3). 13 C NMR (150 MHz, CDCl3) d 156.04 (s), 154.61 (s),
153.41 (s), 130.53 (s), 128.74 (s), 128.26 (s), 124.94 (s), 124.71 (s),
119.50 (s), 104.45 (s), 103.28 (s), 98.76 (s), 55.58 (s). MS: m/z (%)
[M þ Na]þ 247.7, [2M þ Na]þ 471.7.
3.2.5.13. N, N-diethyl-2-phenylbenzofuran-6-amine (13). White
1
solid, yield 90.1%. H NMR (600 MHz, DMSO-d6) d 7.80 (dd, J ¼ 8.3,
1.1 Hz, 2H, Ar), 7.44 (t, 2H, Ar), 7.39 (d, J ¼ 8.6 Hz, 1H, Ar), 7.30 (t,
1H, Ar), 7.21 (d, J ¼ 0.6 Hz, 1H, Ar), 6.82 (d, J ¼ 1.8 Hz, 1H, Ar), 6.69
(dd, J ¼ 8.7, 2.2 Hz, 1H, Ar), 3.38 (q, J ¼ 7.0 Hz, 4H, CH2), 1.11 (t, 6H,
CH3). 13 C NMR (150 MHz, DMSO-d6) d 156.73 (s), 152.18 (s), 146.29
(s), 130.48 (s), 128.90 (s), 127.54 (s), 123.63 (s), 121.24 (s), 117.69
(s), 109.64 (s), 101.96 (s), 93.46 (s), 44.19 (s), 12.39 (s). HR-MS: m/z
(%) [M þ H]þ 266.1215.
3.2.5.6. 4,6-Dimethoxy-2-phenylbenzofuran (6). White solid, yield
1
94.1%. H NMR (600 MHz, CDCl3) d 7.81 (dd, J ¼ 8.3, 1.1 Hz, 2H, Ar),
7.43 (m, 2H, Ar), 7.31 (m, 1H, Ar), 7.05 (d, J ¼ 0.7 Hz, 1H, Ar), 6.72
(m, 1H, Ar), 6.35 (d, J ¼ 1.9 Hz, 1H, Ar), 3.94 (s, 3H, OCH3), 3.88 (s,
3H, OCH3). 13 C NMR (150 MHz, CDCl3) d 159.16 (s), 156.54 (s),
153.65 (s), 153.45 (s), 130.75 (s), 128.70 (s), 127.72 (s), 124.19 (s),
113.22 (s), 98.72 (s), 94.29 (s), 88.20 (s), 55.76 (s), 55.55 (s). MS: m/z
(%) [M þ H]þ 255.6, [M þ Na]þ 277.7, [2M þ Na]þ 531.7.
3.2.5.14. 7-Ethoxy-2-phenylbenzofuran (14). White solid, yield
1
79.1%. H NMR (600 MHz, CDCl3) d 7.92 (dd, J ¼ 8.3, 1.1 Hz, 2H, Ar),
3.2.5.7. 7-Methyl-2-phenylbenzofuran (7). White solid, yield 79.2%.
7.46 (t, 2H, Ar), 7.37 (m, 1H, Ar), 7.17 (m, 2H, Ar), 7.03 (s, 1H, Ar),
1H NMR (600 MHz, CDCl3) d 7.91 (dd, J ¼ 8.3, 1.2 Hz, 2H, Ar), 7.46 6.83 (dd, J ¼ 7.8, 0.9 Hz, 1H, Ar), 4.35 (q, J ¼ 7.0 Hz, 2H, CH2), 1.56