Research Article
RSC Medicinal Chemistry
2H), 7.76 (t, J = 7.7 Hz, 1H), 3.07 (s, 3H). 13C NMR (125 MHz,
DMSO-d6) δ 178.36, 151.06, 144.76, 142.15, 136.25, 130.42,
128.86, 127.21, 126.82, 125.64, 121.48, 31.34. DART-MS: m/z
calcd. for C12H13N4S (M + H)+ 245.08554, found 245.08505.
(E)-2-((4-Fluoroisoquinolin-1-yl)methylene)-N-
methylhydrazine-1-carbothioamide (HCT7). 1H NMR (500
MHz, DMSO-d6) δ 11.76 (s, 1H), 9.19 (d, J = 8.6 Hz, 1H), 8.56
(d, J = 1.4 Hz, 1H), 8.56 (s, 1H), 8.34 (d, J = 4.4 Hz, 1H), 8.14
(d, J = 8.3 Hz, 1H), 7.94–7.97 (m, 1H), 7.85–7.89 (m, 1H), 3.06
(d, J = 4.6 Hz, 3H). 13C NMR (125 MHz, DMSO-d6) δ 178.84,
154.73 (d, 1JC–F = 262.2 Hz), 148.03 (d, 3JC–F = 5.2 Hz),
145.84, 131.75, 130.69, 128.10 (d, 2JC–F = 23.3 Hz), 127.75,
178.85, 178.52, 150.83, 150.19, 145.53, 145.20, 145.10, 140.49,
138.40, 130.28, 130.10, 129.16, 128.41, 127.36, 126.27, 126.16,
117.81, 116.96, 113.24, 111.66, 111.18, 110.61, 31.74, 31.59.
DART-MS: m/z calcd. for C12H14N5S (M + H)+ 260.09644,
found 260.09563.
(E)-2-(Isoquinolin-1-ylmethylene)-N,N-dimethylhydrazine-1-
carbothioamide and (Z)-2-(isoquinolin-1-ylmethylene)-N,N-
dimethylhydrazine-1-carbothioamide (HCT11). 1H NMR (500
MHz, DMSO-d6) δ 15.99 (s, 0.33H), 11.26 (br s, 1H), 9.77 (dd,
J = 8.8, 5.1 Hz, 1H), 8.81 (d, J = 8.6 Hz, 0.33H), 8.70 (d, J = 1.7
Hz, 1H), 8.69 (d, J = 1.2 Hz, 0.33H), 8.63 (s, 0.33H), 8.55 (d, J
= 5.5 Hz, 1H), 8.12 (d, J = 8.2 Hz, 0.33H), 8.01–7.96 (m,
1.33H), 7.92 (ddd, J = 8.1, 7.0, 1.1 Hz, 0.33H), 7.88–7.76 (m,
2.33H), 7.72 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 3.43 (s, 1.98H),
3.35 (s, 6H). 13C NMR (125 MHz, DMSO-d6) δ 180.88, 180.81,
151.94, 150.58, 147.81, 142.50, 140.45, 136.86, 136.82, 131.80,
130.77, 129.48, 129.16, 128.21, 128.17 (2C), 127.68, 126.83,
125.87, 124.60, 122.53, 121.93, 42.08 (4C). DART-MS: m/z
calcd. for C13H15N4S (M + H)+ 259.10119, found 259.10080.
(E)-2-((4-Fluoroisoquinolin-1-yl)methylene)-N,N-
4
2
127.35 (d, JC–F = 3.0 Hz), 126.51 (d, JC–F = 14.9 Hz), 119.79
(d, 3JC–F = 4.6 Hz), 31.86. 19F NMR (376 MHz, DMSO-d6) δ
−137.53, extraneous peak found at −134.32. DART-MS: m/z
calcd. for C12H12FN4S (M + H)+ 263.07612, found 263.07520.
(E)-2-((6-Fluoroisoquinolin-1-yl)methylene)-N-
methylhydrazine-1-carbothioamide (HCT8). 1H NMR (500
MHz, DMSO-d6) δ 11.80 (s, 1H), 9.20 (dd, J = 9.4, 5.7 Hz, 1H),
8.55 (d, J = 5.6 Hz, 1H), 8.54 (s, 1H), 8.35 (d, J = 4.7 Hz, 1H),
7.83 (dd, J = 9.2, 3.9 Hz, 2H) 7.60 (td, J = 9.0, 2.7 Hz, 1H),
3.06 (d, J = 4.5 Hz, 3H). 13C NMR (125 MHz, DMSO-d6) δ
178.56, 162.71 (d, 1JC–F = 250.4 Hz), 151.55, 145.22, 143.53,
dimethylhydrazine-1-carbothioamide
and
(Z)-2-((4-
fluoroisoquinolin-1-yl)methylene)-N,N-dimethylhydrazine-1-
carbothioamide (HCT12). 1H NMR (500 MHz, DMSO-d6) δ
15.52 (s, 0.15H), 11.28 (s, 1H), 9.87 (d, J = 8.7 Hz, 1H), 8.87
(d, J = 9.0 Hz, 0.15H), 8.77 (d, J = 1.9 Hz, 0.15H), 8.69 (s, 1H),
8.57 (d, J = 1.6 Hz, 1.15H), 8.23 (d, J = 8.2 Hz, 0.15H), 8.15 (d,
J = 8.2 Hz, 1H), 8.02–8.05 (m, 0.15H), 7.92–7.97 (m, 1.15H),
7.86 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 3.42 (s, 0.90H), 3.36 (s,
6H). 13C NMR (125 MHz, DMSO-d6) δ 180.79, 180.73, 154.60
3
3
138.62 (d, JC–F = 10.6 Hz), 131.28 (d, JC–F = 9.5 Hz), 123.29,
4
2
121.67 (d, JC–F = 5.1 Hz), 119.23 (d, JC–F = 24.8 Hz), 110.89
(d, JC–F = 20.8 Hz), 31.85. 19F NMR (376 MHz, DMSO-d6) δ
2
−106.55, extraneous peak found at −107.74. DART-MS: m/z
calcd. for C12H12FN4S (M + H)+ 263.07612, found 263.07538.
(E)-N-Methyl-2-((5-(methylamino)isoquinolin-1-yl)-
methylene)hydrazine-1-carbothioamide and (Z)-N-methyl-2-
((5-(methylamino)isoquinolin-1-yl)methylene)hydrazine-1-
carbothioamide (HCT9). 1H NMR (500 MHz, DMSO-d6) δ
14.74 (s, 0.15H), 12.22 (s, 1H), 9.39 (br s, 1H), 8.93 (q, J = 4.7
Hz, 0.15H), 8.78 (s, 1H), 8.54 (d, J = 5.9 Hz, 0.15H), 8.50 (d, J
= 6.5 Hz, 1H), 8.38 (s, 1H), 8.17 (s, 0.15H), 8.12 (d, J = 5.9 Hz,
0.15H), 7.82 (d, J = 8.6 Hz, 0.15H), 7.76 (t, J = 8.1 Hz, 1H),
7.69 (s, 1H), 7.56 (t, J = 8.1 Hz, 0.15H), 7.08 (br s, 1H), 6.92
(d, J = 7.7 Hz, 1.15H), 6.72 (d, J = 7.8 Hz, 0.15H), 3.07 (d, J =
4.6 Hz, 3H), 3.02 (d, J = 4.6 Hz, 0.45 H), 2.88 (s, 3H), 2.86 (s,
0.45H). 13C NMR (125 MHz, DMSO-d6) δ 178.84, 178.38,
150.11, 147.37, 145.83 (2C), 145.56, 138.94, 132.45, 130.58,
129.19, 128.23, 128.22, 126.87 (2C), 126.80, 118.47, 117.04,
111.57, 110.13, 109.63, 106.57, 31.59, 31.42, 30.42 (2C).
DART- MS: m/z calcd. for C13H16N5S (M + H)+ 274.11209,
found 274.11104.
1
1
(d, JC–F = 261.7 Hz), 154.13 (d, JC–F = 261.8 Hz), 148.75 (d,
3JC–F = 5.1 Hz), 147.76 (d, 3JC–F = 5.7 Hz), 147.05, 132.52,
4
131.59 (d, JC–F = 5.1 Hz), 131.10, 130.49, 130.30, 128.60 (d,
4JC–F = 3.3 Hz), 128.41 (d, JC–F = 1.0 Hz), 127.90 (d, JC–F =
23.3 Hz), 127.19 (d, 4JC–F = 2.6 Hz), 126.88 (d, 2JC–F = 14.8
Hz), 126.71 (d, 2JC–F = 14.7 Hz), 126.35 (d, 2JC–F = 25.2
4
2
3
3
Hz),124.98, 120.23 (d, JC–F = 4.3 Hz), 119.79 (d, JC–F = 4.7
Hz), 42.04 (4C). 19F NMR (376 MHz, DMSO-d6) δ −134.93,
−138.02. DART-MS: m/z calcd. for C13H14FN4S (M + H)+
277.09177, found 277.09096.
(E)-2-((6-Fluoro-5-(methylamino)isoquinolin-1-yl)-
methylene)-N,N-dimethylhydrazine-1-carbothioamide and (Z)-
2-((6-fluoro-5-(methylamino)isoquinolin-1-yl)methylene)-N,N-
dimethylhydrazine-1-carbothioamide (HCT14). 1H NMR (500
MHz, DMSO-d6) δ 15.96 (s, 0.17H), 11.22 (Br s, 1H), 9.20 (s,
1H), 8.62–8.54 (m, 1.17H), 8.52 (s, 0.17H), 8.34 (d, J = 5.5 Hz,
1H), 8.20 (d, J = 6.2 Hz, 0.17H), 8.07 (dd, J = 9.3, 4.2 Hz,
0.17H), 7.87 (br s, 1H), 7.56 (dd, J = 13.6, 9.2 Hz, 0.17H), 7.33
(dd, J = 13.4, 9.5 Hz, 1H), 6.10 (br s, 0.17H), 5.69 (br s, 1H),
3.41 (s, 1.02H), 3.27 (s, 6H), 3.10 (t, J = 5.5 Hz, 0.51H), 3.05 (t,
J = 5.2 Hz, 3H). A 13C NMR was not obtained. 19F NMR (376
MHz, CDCl3) δ −129.05, −129.53. DART-MS: m/z calcd. for
C14H17FN5S (M + H)+ 306.11832, found 306.11719.
(E)-2-((5-Aminoisoquinolin-1-yl)methylene)-N-
methylhydrazine-1-carbothioamide
and
(Z)-2-((5-
aminoisoquinolin-1-yl)methylene)-N-methylhydrazine-1-
carbothioamide (HCT10). 1H NMR (500 MHz, DMSO-d6) δ
14.80 (s, 0.08H), 11.66 (br s, 1H), 8.95 (d, J = 4.9 Hz, 0.08H),
8.62 (s, 1H), 8.52 (d, J = 5.9 Hz, 0.8H), 8.42 (d, J = 5.8 Hz, 1H),
8.25 (d, J = 3.3 Hz, 1H), 8.18 (s, 0.08H), 8.11–8.15 (m, 1.08H),
7.99 (d, J = 5.9 Hz, 1H), 7.83 (d, J = 8.4 Hz, 0.08H), 7.48 (t, J =
7.9 Hz, 0.08H), 7.43 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 7.6 Hz,
0.08H), 6.91 (dd, J = 7.6, 0.9 Hz, 1H), 6.21 (s, 0.16H), 6.04 (s,
2H), 3.05–3.07 (m, 3.24H). 13C NMR (125 MHz, DMSO-d6) δ
(E)-2-((4-Fluoro-5-(methylamino)isoquinolin-1-yl)-
methylene)-N,N-dimethylhydrazine-1-carbothioamide and (Z)-
2-((4-fluoro-5-(methylamino)isoquinolin-1-yl)methylene)-N,N-
dimethylhydrazine-1-carbothioamide (HCT15). 1H NMR (500
RSC Med. Chem.
This journal is © The Royal Society of Chemistry 2020