Molecules 2021, 26, 3991
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(714.0 mg, 6 mmol) and LiOH
·
H2O (252.0 mg, 6 mmol) in DMSO (10 mL) to give 3e as a
yellow solid (1.9 g, 5.91 mmol, 98% yield). Next, 3e (358.0 mg, 1.1 mmol) was subjected to
General Procedure B using Sn powder (1.3 g, 11.0 mmol) and 12M HCl (8 mL) in EtOH
(8 mL) to give 4e as a black viscous oil (367 mg, 1.26 mmol, 100% yield). A mixture of 4e
(70 mg, 0.24 mmol) and
5 (56.0 mg, 0.24 mmol) were subjected to General Procedure C
using CH3COOH (40 L, 0.72 mmol), NaBH3CN (15.0 mg, 0.24 mmol), and anhydrous
µ
MeOH (2.0 mL) to give 6e as a yellow viscous oil (54 mg, 0.10 mmol, 44% yield). Finally, 6e
(30 mg, 0.06 mmol) was subjected to General Procedure D using hydrazine monohydrate
(30
µ
L, 0.6 mmol), and EtOH (500
µ
L) to give 7e as yellow oil (26 mg, 0.06 mmol, 100%
1
yield). H NMR (500 MHz, CDCl3)
δ 8.56 (dd, J = 4.2, 1.4 Hz, 1H, ArH), 7.93 (dd, J = 8.5,
1.5 Hz, 1H, ArH), 7.53 (d, J = 8.7 Hz, 2H, ArH), 7.30 (dd, J = 8.5, 4.1 Hz, 1H, ArH), 6.93 (d,
J = 8.7 Hz, 2H, ArH), 6.42 (s, 1H, ArH), 6.17 (brs, 1H, NH), 3.88 (s, 3H, OCH3), 3.69 (s, 1H,
CH), 2.79 (t, J = 6.8 Hz, 2H, CH2NH), 1.82–1.57 (m, 4H, CH2CH2), 1.35 (d, J = 6.3 Hz, 3H,
CH3); 13C NMR (126 MHz, CDCl3)
δ 162.9, 150.3, 145.0, 143.8, 134.2 (2C), 133.5, 129.1, 124.1,
123.0, 122.5, 119.2, 115.9 (2C), 105.0, 92.5, 56.8, 48.2, 42.1, 34.2, 29.9, 20.7; HRMS (ESI+): m/z
calcd. for C22H25N4O2+ [M + H]+ 377.1972, found 377.1978.
N4-(5-(4-Fluorophenoxy)-6-methoxyquinolin-8-yl) pentane-1,4-diamine (7f): 7f was synthesized
following General Procedure A using
2 (716.0 mg, 3 mmol), 4-fluorophenol (336.0 mg,
3 mmol) and LiOH H2O (126.0 mg, 3 mmol) in DMSO (5 mL) to give 3f as a yellow solid
·
(1.0 g, 3.18 mmol, 100% yield). Next, 3f (628.5 mg, 2.0 mmol) was subjected to General
Procedure B using Sn powder (2.4 g, 20.0 mmol), and 12M HCl (14 mL) in EtOH (14 mL)
to give 4f as a black viscous oil (400 mg, 1.41 mmol, 70% yield). A mixture of 4f (79.5 mg,
0.28 mmol) and
CH3COOH (32
(2.0 mL) to give 6f as a yellow viscous oil (47 mg, 0.094 mmol, 34% yield). Finally, 6f (35 mg,
5
(64.7 mg, 0.28 mmol) were subjected to General Procedure C using
µL, 0.56 mmol), NaBH3CN (52.5 mg, 0.84 mmol), and anhydrous MeOH
0.07 mmol) was subjected to General Procedure D using hydrazine monohydrate (20
0.42 mmol) and EtOH (1 mL) to give 7f as yellow oil (27 mg, 0.07 mmol, 100% yield). H
µ
L,
1
NMR (500 MHz, CDCl3)
δ 8.51 (d, J = 4.0 Hz, 1H, ArH), 8.01 (d, J = 8.4 Hz, 1H, ArH),
7.25 (dd, J = 7.7, 3.2 Hz, 1H, ArH), 6.90 (t, J = 8.6 Hz, 2H, ArH), 6.79 (dd, J = 9.0, 4.2 Hz, 2H,
ArH), 6.43 (s, 1H, ArH), 6.03 (brs, 1H, NH), 3.88 (s, 3H, OCH3), 3.67 (s, 1H, CH), 2.89 (s, 2H,
CH2NH), 1.89–1.62 (m, 4H, CH2CH2), 1.30 (d, J = 6.0 Hz, 3H, CH3); 13C NMR (126 MHz,
CDCl3)
δ
158.7, 156.1 (d, 1JCF = 177.0 Hz), 150.6, 144.7, 142.7, 125.0, 124.7, 122.2, 116.3 (d,
3JCF = 7.9 Hz), 115.9 (d, JCF = 15.8 Hz) (4C), 115.8, 94.3, 57.1, 48.1, 40.0, 33.8, 24.6, 20.5;
2
19F{1H} NMR (471 MHz, CDCl3) δ −123.31; HRMS (ESI+): m/z calcd. for C21H25FN3O2
+
[M + H]+ 370.1925, found 370.1925.
N4-(5-(4-Fluorophenoxy)-6-methoxyquinolin-8-yl) pentane-1,4-diamine (7g): 7g was synthesized
following General Procedure A using
2 (716.0 mg, 3 mmol), 4-hydroxybenzotrifluoride
(486.0 mg, 3 mmol), and LiOH H2O (126.0 mg, 3 mmol) in DMSO (5 mL) to give 3g as a pale
·
yellow solid (149 mg, 0.41 mmol, 14% yield). Next, 3g (149 mg, 0.41 mmol) was subjected to
General Procedure B using Sn powder (485 mg, 4.09 mmol) and 12M HCl (3.5 mL) in EtOH
(3.5 mL) to give 4g as an orange viscous oil (95 mg, 0.33 mmol, 82% yield). A mixture of 4g
(91 mg, 0.32 mmol) and
5 (148 mg, 0.64 mmol) were subjected to General Procedure C using
CH3COOH (38 L, 0.64 mmol), NaBH3CN (20 mg, 0.32 mmol), and anhydrous MeOH
µ
(3.0 mL) to give 6g as an orange viscous oil (22 mg, 0.04 mmol, 13% yield). Finally, 6g
(22 mg, 0.04 mmol) was subjected to General Procedure D using hydrazine monohydrate
(20
µ
L, 0.40 mmol) and EtOH (1 mL) to give 7g as yellow viscous oil (20 mg, 0.04 mmol,
1
100% yield). H NMR (500 MHz, acetone-d6)
δ
8.72–8.48 (m, 1H, ArH), 8.00 (ddd, J = 8.5,
3.5, 1.7 Hz, 1H, ArH), 7.61 (d, J = 8.0 Hz, 2H, ArH), 7.41 (ddd, J = 8.3, 4.1, 1.5 Hz, 1H,
ArH), 7.01 (d, J = 8.3 Hz, 2H, ArH), 6.71 (dd, J = 16.1, 14.9 Hz, 1H, ArH), 3.91 (dd, J = 4.4,
1.7 Hz, 3H, OCH3), 3.40 3.17 (m, 2H, CH2NH), 2.87 (t, J = 7.0 Hz, 2H, CH), 1.94–1.68 (m,
4H, CH2CH2), 1.35 (d, J = 6.3 Hz, 3H, CH3); 13C NMR (126 MHz, acetone-d6)
144.6, 144.0, 133.4, 131.0, 128.7 (q, JCF = 4.1 Hz), 126.9 (q, JCF = 65.1 Hz), 124.0, 122.9,
δ
150.7, 144.8,
3
2