Journal of Medicinal Chemistry
Article
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product was obtained as a white solid in 59.1% yield. H NMR (400
MHz, chloroform-d) δ 8.13 (d, J = 9.0 Hz, 1H), 7.87 (s, 1H), 7.43 (d,
J = 8.1 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.96 (dd, J = 9.0, 2.3 Hz,
1H), 6.70 (d, J = 2.2 Hz, 1H), 3.92−3.83 (m, 4H), 3.36−3.29 (m,
4H), 2.36 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ 175.77,
158.16, 154.92, 152.19, 137.83, 129.14, 128.85, 127.44, 125.07,
113.08, 100.15, 66.50, 47.64, 21.27. HRMS (ESI): m/z calcd for
C20H20O3N [M + H]+, 322.1433; found, 322.1438.
1.65−1.54 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
chloroform-d) δ 177.23, 158.66, 151.28, 150.71, 126.94, 123.60,
113.65, 110.97, 96.45, 47.75, 29.73, 27.87, 25.48, 21.73, 13.89. HRMS
(ESI): m/z calcd for C16H20O2N [M + H]+, 258.1486; found,
258.1489.
7-(Piperidin-1-yl)-3-propyl-4H-chromen-4-one (III7). Compound
(III7) was prepared according to the general procedure and the
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product was obtained as a white solid in 53.8% yield. H NMR (400
7-(Diethylamino)-3-methyl-4H-chromen-4-one (II3). Compound
(II3) was prepared according to the general procedure and the
product was obtained as a white solid in 28.1% yield. H NMR (400
MHz, chloroform-d) δ 7.99 (d, J = 9.1 Hz, 1H), 7.58 (q, J = 1.2 Hz,
1H), 6.69 (dd, J = 9.1, 2.5 Hz, 1H), 6.38 (d, J = 2.5 Hz, 1H), 3.40 (q,
J = 7.1 Hz, 4H), 1.96 (d, J = 1.2 Hz, 3H), 1.20 (t, J = 7.1 Hz, 6H). 13C
NMR (101 MHz, chloroform-d) δ 177.51, 159.18, 150.43, 126.95,
119.81, 110.39, 96.18, 44.73, 29.72, 12.47, 11.26. HRMS (ESI): m/z
calcd for C14H18O2N [M + H]+, 232.1328; found, 232.1332.
MHz, chloroform-d) δ 7.99 (d, J = 9.1 Hz, 1H), 7.56 (s, 1H), 6.90
(dd, J = 9.1, 2.3 Hz, 1H), 6.60 (d, J = 2.1 Hz, 1H), 3.32 (d, J = 5.4 Hz,
4H), 2.41−2.33 (m, 2H), 1.65 (m, 6H), 1.56 (dt, J = 14.8, 7.5 Hz,
2H), 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, chloroform-d) δ
177.12, 158.64, 154.83, 151.04, 126.69, 123.85, 113.20, 99.71, 48.81,
27.83, 25.30, 24.31, 21.69, 13.87. HRMS (ESI): m/z calcd for
C17H22O2N [M + H]+, 272.1642; found, 272.1645.
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7-Morpholino-3-propyl-4H-chromen-4-one (III8). Compound
(III8) was prepared according to the general procedure and the
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3-Methyl-7-(pyrrolidin-1-yl)-4H-chromen-4-one (II4). Compound
(II4) was prepared according to the general procedure and the
product was obtained as a white solid in 56.7% yield. H NMR (400
MHz, DMSO-d6) δ 8.00 (s, 1H), 7.80 (d, J = 9.1 Hz, 1H), 7.06 (dd, J
= 9.1, 2.3 Hz, 1H), 6.81 (d, J = 2.3 Hz, 1H), 3.32−3.24 (m, 4H),
2.29−2.20 (m, 2H), 1.46 (h, J = 7.4 Hz, 2H), 0.84 (t, J = 7.4 Hz, 3H).
13C NMR (100 MHz, DMSO-d6) δ 176.10, 158.35, 155.02, 152.73,
126.33, 123.31, 115.22, 113.17, 100.11, 66.24, 47.36, 27.52, 21.74,
14.12. HRMS (ESI): m/z calcd for C16H20O3N [M + H]+, 274.1429;
found, 274.1438.
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product was obtained as a white solid in 59.3% yield. H NMR (400
MHz, DMSO-d6) δ 7.96 (s, 1H), 7.76 (d, J = 8.9 Hz, 1H), 6.65 (dd, J
= 8.9, 2.2 Hz, 1H), 6.33 (d, J = 2.1 Hz, 1H), 3.30−3.27 (m, 4H),
1.95−1.91 (m, 4H), 1.80 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ
176.43, 158.68, 151.72, 151.47, 126.41, 119.23, 111.70, 96.76, 47.91,
25.40, 11.27. HRMS (ESI): m/z calcd for C14H16O2N [M + H]+,
230.1173; found, 230.1173.
7-(Diethylamino)-6-methoxy-3-(p-tolyl)-4H-chromen-4-one
(IV3). Compound (IV3) was prepared according to the general
procedure and the product was obtained as a white solid in 25.9%
3-Methyl-7-(piperidin-1-yl)-4H-chromen-4-one (II5). Compound
(II5) was prepared according to the general procedure and the
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product was obtained as a white solid in 53.2% yield. H NMR (400
yield. H NMR (400 MHz, chloroform-d) δ 7.89 (s, 1H), 7.57 (s,
MHz, chloroform-d) δ 8.00 (d, J = 9.1 Hz, 1H), 7.61 (q, J = 1.2 Hz,
1H), 6.91 (dd, J = 9.1, 2.4 Hz, 1H), 6.61 (d, J = 2.3 Hz, 1H), 3.34 (t, J
= 5.2 Hz, 4H), 1.96 (d, J = 1.2 Hz, 3H), 1.71−1.60 (m, 6H). 13C
NMR (101 MHz, chloroform-d) δ 154.80, 150.77, 126.62, 120.08,
113.25, 99.77, 48.83, 25.30, 24.30, 11.24. HRMS (ESI): m/z calcd for
C15H18O2N [M + H]+, 244.1329; found, 244.1332.
1H), 7.46 (d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.3 Hz, 2H), 6.78 (s, 1H),
3.95 (s, 3H), 3.36 (q, J = 7.0 Hz, 4H), 2.38 (s, 3H), 1.16 (t, J = 7.0
Hz, 6H). 13C NMR (101 MHz, chloroform-d) δ 175.45, 152.49,
151.82, 150.35, 146.17, 137.65, 129.11, 128.87, 124.36, 117.31,
105.67, 105.05, 56.00, 45.81, 29.73, 21.28, 12.45. HRMS (ESI): m/z
calcd for C21H24O3N [M + H]+, 338.1751; found, 338.1746.
3-Methyl-7-morpholino-4H-chromen-4-one (II6). Compound
(II6) was prepared according to the general procedure and the
7-(Azetidin-1-yl)-6-methoxy-3-(p-tolyl)-4H-chromen-4-one (IV4).
Compound (IV4) was prepared according to the general procedure
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product was obtained as a white solid in 61.2% yield. H NMR (400
and the product was obtained as a white solid in 32.7% yield. H
MHz, DMSO-d6) δ 8.04 (s, 1H), 7.80 (d, J = 8.9 Hz, 1H), 7.06 (dd, J
= 9.1, 2.3 Hz, 1H), 6.81 (d, J = 2.1 Hz, 1H), 3.70 (t, J = 4.7 Hz, 4H),
3.28 (t, J = 4.9 Hz, 4H), 1.82 (s, 3H). 13C NMR (101 MHz, DMSO-
d6) δ 176.54, 158.52, 154.99, 152.35, 126.23, 119.60, 114.96, 113.17,
100.10, 66.25, 47.33, 11.22. HRMS (ESI): m/z calcd for C14H16O3N
[M + H]+, 246.1119; found, 246.1125.
NMR (400 MHz, chloroform-d) δ 7.84 (s, 1H), 7.47 (s, 1H), 7.46 (d,
J = 3.1 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 6.20 (s, 1H), 4.18−4.10 (m,
4H), 3.87 (s, 3H), 2.43−2.31 (m, 5H). 13C NMR (101 MHz,
chloroform-d) δ 175.23, 153.24, 151.35, 147.57, 146.59, 137.53,
129.74, 129.07, 128.88, 124.23, 115.46, 104.40, 98.02, 55.83, 54.10,
21.27, 17.44. HRMS (ESI): m/z calcd for C20H20O3N [M + H]+,
322.14377; found, 322.14435
7-(Diethylamino)-3-propyl-4H-chromen-4-one (III4). Compound
(III4) was prepared according to the general procedure and the
6-Methoxy-7-(pyrrolidin-1-yl)-3-(p-tolyl)-4H-chromen-4-one
(IV5). Compound (IV5) was prepared according to the general
procedure and the product was obtained as a white solid in 41.7%
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product was obtained as a white solid in 39.8% yield. H NMR (400
MHz, chloroform-d) δ 8.00 (d, J = 9.1 Hz, 1H), 7.54 (t, J = 0.8 Hz,
1H), 6.70 (dd, J = 9.1, 2.5 Hz, 1H), 6.40 (s, 1H), 3.41 (q, J = 7.1 Hz,
4H), 2.41−2.32 (m, 2H), 1.63−1.53 (m, 2H), 1.20 (t, J = 7.1 Hz,
6H), 0.94 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, chloroform-d) δ
177.04, 158.95, 150.72, 129.05, 128.24, 127.06, 123.64, 110.40, 96.29,
44.79, 29.72, 27.84, 21.74, 13.87, 12.46. HRMS (ESI): m/z calcd for
C16H22O2N [M + H]+, 260.1643; found, 260.1645.
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yield. H NMR (400 MHz, chloroform-d) δ 7.82 (s, 1H), 7.49 (s,
1H), 7.46 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.44 (s, 1H),
3.88 (s, 3H), 3.52 (t, J = 6.5 Hz, 4H), 2.37 (s, 3H), 1.95 (t, J = 4.5 Hz,
4H); 13C NMR (100 MHz, chloroform-d) δ 175.14, 153.37, 151.39,
147.81, 145.05, 137.48, 129.83, 129.06, 128.89, 124.20, 114.81,
104.98, 99.87, 56.00, 50.81, 25.50, 21.28. HRMS (ESI): m/z calcd for
C21H22O3N [M + H]+, 336.1585; found, 336.1594.
6-Methoxy-7-(piperidin-1-yl)-3-(p-tolyl)-4H-chromen-4-one
(IV6). Compound (IV6) was prepared according to the general
procedure and the product was obtained as a white solid in 43.1%
yield. 1H NMR (400 MHz, chloroform-d) δ 7.90 (d, J = 1.0 Hz, 1H),
7.57 (s, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.85
(s, 1H), 3.95 (s, 3H), 3.17−3.09 (m, 4H), 2.37 (s, 3H), 1.77 (p, J =
5.8 Hz, 4H), 1.62 (p, J = 5.8 Hz, 2H); 13C NMR (100 MHz,
chloroform-d) δ 175.57, 152.35, 152.01, 150.45, 148.75, 137.70,
129.48, 129.13, 128.86, 124.44, 118.48, 106.01, 104.84, 56.06, 51.76,
25.99, 24.30, 21.29. HRMS (ESI): m/z calcd for C22H24O3N [M +
H]+, 350.1744; found, 350.1751.
7-(Azetidin-1-yl)-3-propyl-4H-chromen-4-one (III5). Compound
(III5) was prepared according to the general procedure and the
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product was obtained as a white solid in 43.4% yield. H NMR (400
MHz, chloroform-d) δ 8.01 (d, J = 8.8 Hz, 1H), 7.56 (s, 1H), 6.41
(dd, J = 8.8, 2.2 Hz, 1H), 6.16−6.12 (m, 1H), 4.03−3.97 (m, 4H),
2.47−2.36 (m, 4H), 1.59 (h, J = 7.4 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H).
13C NMR (101 MHz, chloroform-d) δ 150.93, 127.10, 123.85,
114.69, 109.63, 95.79, 77.16, 51.78, 27.96, 21.82, 16.64, 13.99. HRMS
(ESI): m/z calcd for C15H18O2N [M + H]+, 244.1332; found,
244.1323.
3-Propyl-7-(pyrrolidin-1-yl)-4H-chromen-4-one (III6). Compound
(III6) was prepared according to the general procedure and the
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product was obtained as a white solid in 54.6% yield. H NMR (400
6-Methoxy-7-morpholino-3-(p-tolyl)-4H-chromen-4-one (IV7).
Compound (IV7) was prepared according to the general procedure
MHz, chloroform-d) δ 8.04 (d, J = 8.9 Hz, 1H), 7.56 (t, J = 0.9 Hz,
1H), 6.61 (dd, J = 8.9, 2.2 Hz, 1H), 6.29 (d, J = 2.2 Hz, 1H), 3.41−
3.32 (m, 4H), 2.39 (td, J = 7.5, 0.8 Hz, 2H), 2.09−2.01 (m, 4H),
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and the product was obtained as a white solid in 47.3% yield. H
NMR (400 MHz, chloroform-d) δ 7.91 (s, 1H), 7.60 (s, 1H), 7.45 (d,
K
J. Med. Chem. XXXX, XXX, XXX−XXX