Journal of Medicinal Chemistry
Article
procedure 1. Yield: 31%. State: red solid. UPLC-MS method B: Rt:
1.96, MS (ESI)+: 328.2−330.2 [M + H]+. 1H NMR (500 MHz,
CDCl3): 8.22 (dd, J = 7.7, 0.9 Hz, 1H), 8.14 (dd, J = 7.6, 0.9 Hz, 1H),
7.78 (td, J = 26.4, 16.3, 1.3 Hz, 1H), 7.76−7.59 (m, 2H), 7.24 (d, J =
8.3 Hz, 2H), 7.06 (d, J = 8.2 Hz, 2H), 3.91 (t, J = 6.5 Hz, 2H), 2.92
(t, J = 6.5 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 180.5, 177.4,
141.5, 136.2, 135.8, 135.1, 133.0, 132.6, 129.9, 129.0, 127.1, 127.0,
124.5, 63.5, 38.7.
7.6, 0.9 Hz, 1H), 8.09−8.04 (m, 1H), 7.72 (td, J = 7.5, 1.3 Hz, 1H),
7.64 (td, J = 7.5, 1.4 Hz, 1H), 7.33−7.27 (m, 2H), 7.15 (s, 1H),
7.12−7.09 (m, 1H), 7.08−7.03 (m, 2H), 3.68 (t, J = 6.7 Hz, 2H),
1.36−1.22 (m, 2H), 0.65 (t, J = 7.4 Hz, 3H). 13C NMR (125 MHz,
CDCl3) δ: 183.2, 179.8, 143.3, 138.8, 134.5, 132.6, 132.3, 130.5,
130.3, 128.9, 128.2, 126.3, 126.2, 125.6, 123.9, 122.4, 74.6, 22.8, 10.0.
2-Isopropoxy-3-(phenylamino)naphthalene-1,4-dione (44). The
title compound was obtained according to the general procedure 3.
Yield: 63%. State: orange solid. UPLC-MS method C: Rt: 1.22, MS
(ESI)+: 308 [M + H]+. 1H NMR (500 MHz, CDCl3) δ: 8.11 (dd, J =
7.6, 1.4 Hz, 1H), 8.07 (dd, J = 7.7, 1.4 Hz, 1H), 7.74−7.69 (m, 1H),
7.65−7.60 (m, 1H), 7.41 (dd, J = 5.0, 2.0 Hz, 1H), 7.33−7.28 (m,
2H), 7.20 (bs, 1H), 7.13−7.05 (m, 2H), 7.05−7.00 (m, 2H), 4.41−
4.21 (m, 1H), 0.88 (d, J = 6.1 Hz, 6H). 13C NMR (125 MHz, CDCl3)
δ: 181.3, 178.4, 141.4, 136.6, 135.4, 133.1, 132.6, 130.7, 130.3, 128.6,
128.5, 127.1, 126.5, 126.2, 124.4, 124.3, 123.6, 121.9, 120.8, 73.1,
19.9.
2-Chloro-3-(3-methyl-4-phenoxyphenoxy)naphthalene-1,4-
dione (37). The title compound was obtained according to the
general procedure 1. Yield: 32%, purity 94%. State: red solid. UPLC-
1
MS method B: Rt: 2.70, MS (ESI)+: 391.4−393.4 [M + H]+. H
NMR (500 MHz, CDCl3) δ: 8.14 (dd, J = 7.7, 0.9 Hz, 1H), 8.07 (dd,
J = 7.7, 0.9 Hz, 1H), 7.72 (td, J = 7.6, 1.3 Hz, 1H), 7.65 (td, J = 7.6,
1.3 Hz, 1H), 7.54 (s, 1H), 7.34 (d, J = 2.6 Hz, 1H), 7.31−7.23 (m,
2H), 7.10 (dd, J = 8.8, 2.7 Hz, 1H), 6.96−6.89 (m, 2H), 6.84 (d, J =
8.8 Hz, 1H), 1.47 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 179.5,
138.5, 135.2, 133.4, 133.2, 130.0, 129.0, 127.3, 127.1, 123.3, 120.5,
119.2, 17.3.
2-Phenoxy-3-(phenylamino)naphthalene-1,4-dione (45). The
title compound was obtained according to the general procedure 3.
Yield: 52%. State: red solid. UPLC-MS method C: Rt: 2.34, MS
2-Chloro-3-((4-methoxy-3-(trifluoromethyl)phenyl)amino)-
naphthalene-1,4-dione (38). The title compound was obtained
according to the general procedure 1. Yield: 34%. State: red solid.
UPLC-MS method B: Rt: 2.41, MS (ESI)+: 382.2−384.1 [M + H]+.
1H NMR (500 MHz, CDCl3) δ: 8.24 (d, J = 7.1 Hz, 1H), 8.16 (d, J =
7.05 Hz, 2H), 7.81 (dt, J = 7.7 Hz, 1H), 7.73 (dt, J = 7.7, 1 Hz, 1H),
7.62 (bs, 1H), 7.37 (d, J = 7.9 Hz, 2H), 7.26 (d, J = 8.2 1H), 3.97 (s,
1H). 13C NMR (125 MHz, CDCl3) δ: 180.3, 179.0, 138.5, 135.15,
133.04, 129.54, 127.21, 127.04, 123.92, 111.87, 56.27.
2-Chloro-3-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-
naphthalene-1,4-dione (39). The title compound was obtained
according to the general procedure 1. Yield: 34%. State: red solid.
UPLC-MS MS method C: Rt: 2.06, MS (ESI)+: 370−372 [M + H]+.
1H NMR (500 MHz, CDCl3) δ: 8.18−8.10 (m, 1H), 8.07 (dd, J = 7.7,
1.4 Hz, 1H), 7.76−7.70 (m, 1H), 7.66 (td, J = 7.6, 1.4 Hz, 1H), 7.52
(s, 1H), 7.26 (dd, J = 6.1, 2.7 Hz, 1H), 7.18−7.10 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ: 180.16, 176.62, 141.19, 135.28, 133.69, 133.31,
132.69, 132.37, 129.73, 129.48, 127.15, 126.35, 122.90, 116.97,
103.84.
2-Hydroxy-3-(phenylamino)naphthalene-1,4-dione (40). The
title compound was obtained according to the general procedure 3.
Yield: 76%. State: purple solid. UPLC-MS method C: Rt: 1.14, MS
(ESI)+: 266 [M + H]+. 1H NMR (500 MHz, CDCl3) δ: 8.13 (dd, J =
7.7, 1.4 Hz, 1H), 8.05 (dd, J = 7.7, 1.4 Hz, 1H), 7.68 (dd, J = 7.6, 1.4
Hz, 1H), 7.65 (dd, J = 7.6, 1.4 Hz, 1H), 7.28 (dd, J = 8.5, 7.4 Hz,
2H), 7.15 (s, 1H), 7.15−7.08 (m, 1H), 7.08−7.02 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ: 183.2, 179.7, 139.4, 138.7, 134.6, 133.8, 132.7,
132.2, 130.1, 128.3, 126.3, 126.2, 124.1, 122.2, 59.92.
2-Methoxy-3-(phenylamino)naphthalene-1,4-dione (41). The
title compound was obtained according to the general procedure 3.
Yield: 80%. State: orange solid. UPLC-MS method C: Rt: 1.15, MS
(ESI)+: 280 [M + H]+. 1H NMR (500 MHz, CDCl3) δ: 8.11 (dd, J =
7.7, 1.4 Hz, 1H), 8.07 (dd, J = 7.7, 1.4 Hz, 1H), 7.72 (dd, J = 7.6, 1.4
Hz, 1H), 7.66 (dd, J = 7.6, 1.4 Hz, 1H), 7.31 (dd, J = 8.5, 7.4 Hz,
2H), 7.18 (s, 1H), 7.15−7.08 (m, 1H), 7.08−7.02 (m, 2H), 3.52 (s,
3H). 13C NMR (125 MHz, CDCl3) δ: 183.2, 179.7, 139.4, 138.7,
134.6, 133.8, 132.7, 132.2, 130.17, 128.31, 126.31, 126.28, 124.06,
122.22, 59.92.
2-Ethoxy-3-(phenylamino)naphthalene-1,4-dione (42). The title
compound was obtained according to the general procedure 3. Yield:
64%. State: orange solid. UPLC-MS method C: Rt: 1.14, MS (ESI)+:
296 [M + H]+. 1H NMR (500 MHz, CDCl3) δ: 8.11 (dd, J = 7.6, 1.3
Hz, 1H), 8.07 (dd, J = 7.6, 1.4 Hz, 1H), 7.72 (td, J = 7.5, 1.3 Hz, 1H),
7.70−7.62 (m, 1H), 7.36−7.28 (m, 2H), 7.16−6.94 (m, 3H), 3.74 (q,
J = 7.0 Hz, 2H), 0.85 (t, J = 7.0 Hz, 3H). 13C NMR (125 MHz,
CDCl3) δ: 183.3, 179.9, 143.3, 138.6, 134.5 134.5, 132.6, 132.5, 130.5
130.3, 128.9, 128.4, 126.2, 125.4, 124.1, 122.8, 68.5, 14.6.
2-(Phenylamino)-3-propoxynaphthalene-1,4-dione (43). The
title compound was obtained according to the general procedure 3.
Yield: 67%. State: orange solid. UPLC-MS method C: Rt: 2.45, MS
(ESI)+: 308 [M + H]+. 1H NMR (500 MHz, CDCl3) δ: 8.10 (dt, J =
1
(ESI)+: 342 [M + H]+. H NMR (500 MHz, CDCl3) δ: 8.18−8.11
(m, 1H), 7.82−7.71 (m, 2H), 7.69 (dd, J = 7.6, 1.3 Hz, 1H), 7.17 (t, J
= 7.8 Hz, 2H), 7.10−7.00 (m, 3H), 6.96 (dd, J = 7.4, 1.7 Hz, 2H),
6.90 (dd, J = 8.7, 1.1 Hz, 1H), 6.88−6.80 (m, 1H), 6.58−6.46 (m,
2H). 13C NMR (125 MHz, CDCl3) δ: 183.5, 179.9, 142.4, 138.9,
135.5, 134.9, 132.7, 129.0, 128.0, 127.6, 127.11, 126.8, 126.5, 125.0,
124.2, 123.7, 121.9, 120.4, 119.3.
2-(Methylamino)-3-(phenylamino)naphthalene-1,4-dione (46).
The title compound was obtained according to the general procedure
3. Yield: 45%. State: purple solid. UPLC-MS method C: Rt: 1.16, MS
1
(ESI)+: 279 [M + H]+. H NMR (500 MHz, CDCl3) δ: 8.21−7.99
(m, 2H), 7.63 (m, 1H), 7.32−7.15 (m, 2H), 6.98−6.84 (m, 2H), 6.75
(m, 2H), 6.42 (s, 1H), 2.73 (dd, J = 5.7, 2.5 Hz, 3H). 13C NMR (125
MHz, DMSO) δ: 181.9, 181.1, 143.6, 137.8, 134.1, 132.6, 132.1,
130.9, 129.0, 128.4, 126.2, 126.1, 120.4, 120.3, 116.5, 113.8, 30.4.
2-(Ethylamino)-3-(phenylamino)naphthalene-1,4-dione (47).
The compound was obtained according to the general procedure 3.
Yield: 35%. State: purple solid. UPLC-MS method C: Rt: 1.21, MS
1
(ESI)+: 293 [M + H]+. H NMR (500 MHz, CDCl3) δ: 8.06−8.23
(m, 2H), 7.64−7.62 (m, 2H), 7.43−7.41 (m, 2H), 6.98−6.84 (m,
2H), 6.42 (s, 1H), 3.14−2.96 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H). 13C
NMR (125 MHz, CDCl3) δ: 188.9, 182.1, 143.3, 143.3, 134.8, 134.0,
133.5, 132.6, 130.5, 128.9, 127.4, 126.3, 126.2, 126.1, 125.4, 37.8,
15.7.
2-(Dimethylamino)-3-(phenylamino)naphthalene-1,4-dione
(48). The title compound was obtained according to the general
procedure 3. Yield: 49%. State: purple solid. UPLC-MS method C: Rt:
1
2.48, MS (ESI)+: 293 [M + H]+. H NMR (500 MHz, CDCl3) δ:
8.09−7.89 (m, 2H), 7.62 (m, 2H), 7.39−7.18 (m, 2H), 7.19−7.06
(m, 1H), 7.04−6.95 (m, 1H), 6.91−6.71 (m, 2H), 2.74 (s, 6H). 13C
NMR (125 MHz, CDCl3) δ: 182.1, 181.9, 140.2, 133.5, 133.3, 132.7,
130.8, 128.8, 128.2, 127.4, 126.3, 125.5, 121.8, 121.6, 41.0.
2-((4-Fluoro-3-(trifluoromethyl)phenyl)amino)-3-methoxynaph-
thalene-1,4-dione (49). The title compound was obtained according
to the general procedure 3. Yield: 78%. State: red solid. UPLC-MS
method C: Rt: 2.41, MS (ESI)+: 366 [M + H]+. 1H NMR (500 MHz,
chloroform-d) δ 8.05−8.02 (m, 1H), 8.00 (dt, J = 7.7, 0.8 Hz, 1H),
7.68 (td, J = 7.5, 1.4 Hz, 1H), 7.60 (td, J = 7.5, 1.3 Hz, 1H), 7.21 (dd,
J = 6.0, 2.8 Hz, 1H), 7.15−7.05 (m, 2H), 7.02 (s, 1H), 3.57 (s, 3H).
13C NMR (126 MHz, CDCl3) δ: 182.72, 179.77, 135.20, 134.73,
133.19, 133.00, 130.00, 127.32, 126.44, 120.68, 120.63, 116.84, 60.14.
2-((2-Fluoro-5-(trifluoromethyl)phenyl)amino)-3-methoxynaph-
thalene-1,4-dione (50). The title compound was obtained according
to the general procedure 3. Yield: 72%. Purity: 91%. State: red solid.
UPLC-MS method C: Rt: 2.45, MS (ESI)+: 366 [M + H]+. 1H NMR
(500 MHz, CDCl3) δ: 8.07−7.95 (m, 1H), 7.72−7.64 (m, 1H), 7.62
(dd, J = 7.5, 1.4 Hz, 1H), 7.59−7.52 (m, 2H), 7.35 (m, 2H), 6.96 (s,
1H), 3.68 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 182.3, 179.9,
143.4, 134.8, 134.6, 133.1, 132.3, 131.9, 130.5, 130.0, 128.9, 128.4,
126.4, 126.3, 125.4, 121.5, 120.9, 115.5, 60.2.
N
J. Med. Chem. XXXX, XXX, XXX−XXX