JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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þ
30.68 (CH2); 32.63 (CH2); 42.57 (CH2); 43.39 (CH2); 126.22 (CHAr); HRMS (m/z) [M þ H]þ: calculated for C13H20N3
218.1652;
found 218.1654.
128.54 (CHAr); 140.62 (CAr); 159.67 (C¼N) ppm. ESI-HRMS (m/z)
þ
[M þ H]þ: calculated for C12H18N3 204.1495; found 204.1498.
N-(4-Chlorobenzyl)-1-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 13. White solid, m.p. 84 ꢀC. [1H]-NMR (MeOD) d: 2.96
(s, 3H, CH3), 3.61–3.76 (m, 4H, CH2CH2), 4.41 (s, 2H, CH2), 7.31 (d,
J ¼ 8.4 Hz, 2H, Ar), 7.35 (d, J ¼ 8.4 Hz, 2H, Ar), 7.42 (s, 2H, NH) ppm.
[13C]-NMR (MeOD) d: 30.68 (CH3), 40.95 (CH2), 45.41 (CH2), 50.09
(CH2), 128.92 (CHAr), 130.37 (CHAr), 133.46 (CCl), 135.00 (CAr),
158.68 (C¼N), ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for
N-Benzyl-N-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroio-
dide 6. Purification by flash chromatography (CH2Cl2/CH3OH/NH3
80:20:1 as eluent). White solid; m.p. 150–153 ꢀC. [1H]-NMR (D2O) d:
2.89 (s, 3H, NCH3); 3.61 (s, 4H, CH2CH2); 4.42 (s, 2H, CH2Ph);
7.15–7.40 (m, 5H, Ar) ppm. [13C]-NMR (D2O) d: 36.38 (CH3); 43.14
(2CH2); 54.29 (CH2Ph); 127.05 (CHAr); 128.25 (CHAr); 129.11 (CHAr);
134.71 (CAr); 160.548 (C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ: calcu-
þ
C11H15ClN3 224.0949; found 224.0946.
þ
N-(4-Methoxybenzyl)-1-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 14. White solid, m.p. 167 ꢀC. [1H]-NMR (CDCl3) d: 3.18
(s, 3H, CH3), 3.64 (s, 4H, CH2CH2), 3.76 (s, 3H, OCH3), 4.58 (d,
J ¼ 5.7 Hz, 2H, CH2), 6.38 (s, 1H, NH), 6.85 (d, J ¼ 8.6 Hz, 2H, Ar),
7.39 (d, J ¼ 8.6 Hz, 2H, Ar), 8.10 (s, 1H, NH), ppm. [13C]-NMR (CDCl3)
d: 33.77 (NCH3), 41.29 (CH2), 45.86 (CH2), 50.14 (CH2), 55.36 (OCH3),
114.38 (CHAr), 127.62 (CAr), 129.69 (CHAr), 158.19 (CAr), 159.59
(C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for C12H18N3Oþ
220.1444; found 220.1443.
lated for C11H16N3 190.1339; found 190.1342.
N-Methyl-N-phenethyl-4,5-dihydro-1H-imidazol-2-amine hydro-
iodide 7. White solid; m.p. 200–204 ꢀC. [1H]-NMR (D2O) d: 2.80 –
2.89 (m, 5H, NCH3
þ PhCH2); 3.42 (s, 4H, 2CH2); 3.46 (t, J ¼ 6.6 Hz,
2H, NCH2); 7.19–7.33 (m, 5H, Ar) ppm. [13C]-NMR (D2O) d: 32.62
(CH2Ph); 36.19 (NCH3); 42.83 (N-CH2); 52.53 (CH2CH2); 126.98
(CHAr); 128.82 (CHAr); 129.05 (CHAr); 138.13 (CAr); 159.89 (C¼N)
ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for C12H18N3 204.1495;
þ
found 204.1499.
N-(4-Fluorobenzyl)-1-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 15. White solid, m.p. 157 ꢀC. [1H]-NMR (MeOD) d: 2.97
(s, 3H, CH3), 3.61 – 3.75 (m, 4H, CH2CH2), 4.42 (s, 2H, CH2), 7.08 (t,
J ¼ 8.5 Hz, 2H, Ar), 7.42 (dd, J ¼ 8.5, 5.4 Hz, 2H, Ar), ppm. [13C]-NMR
(MeOD) d: 30.81 (CH3), 40.98 (CH2), 45.44 (CH2), 50.11 (CH2), 115.26
(d, JC-F ¼ 22 Hz, CHAr), 129.12 (d, JC-F ¼ 8 Hz, CHAr), 132.25 (CAr),
158.62 (C¼N), 162.48 (d, JC-F ¼ 244 Hz, CF), ppm. ESI-HRMS (m/z)
1-Methyl-N-phenethyl-4,5-dihydro-1H-imidazol-2-amine hydroio-
dide 8. White solid; m.p. 118–220 ꢀC. [1H]-NMR (CDCl3) d:
3.00–3.08 (m, 5H, PhCH2 þ NCH3); 3.48 (s, 4H, 2CH2); 3.65 (appar-
ent q, J ¼ 6.8 Hz, 2H, NCH2); 6.96 (s, 1H, NH), 7.12–7.35 (m, 5H, Ar),
7.49 (t, J ¼ 5.6, 1H, NH) ppm. [13C]-NMR (CDCl3) d: 33.78 (CH3);
35.49 (CH2); 41.04 (CH2); 45.22 (CH2); 50.11 (CH2); 126.79 (CHAr);
128.67 (CHAr); 129.32 (CHAr); 137.87 (CAr); 158.22 (C¼N) ppm. ESI-
[M þ H]þ: calculated for C11H15FN3 208.1245; found 208.1245.
þ
HRMS (m/z) [M þ H]þ: calculated for C12H18N3
204.1495;
þ
N-(3-Chlorobenzyl)-1-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 16. White solid, m.p. 190 ꢀC. [1H]-NMR (MeOD) d: 2.96
(s, 3H, CH3), 3.58–3.71 (m, 4H), 4.41 (s, 2H, CH2), 7.20–7.25 (m, 1H,
Ar), 7.25–7.37 (m, 3H, Ar) ppm. [13C]-NMR (MeOD) d: 30.56 (CH3),
40.93 (CH2), 45.45 (CH2), 50.06 (CH2), 125.25 (CHAr), 126.91 (CHAr),
127.74 (CHAr), 130.07 (CHAr), 134.35 (C-Cl), 138.59 (CAr), 154.1þ0
(C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for C11H15ClN3
224.0949; found 224.0949.
N-(3-Methoxybenzyl)-1-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 17. White solid, m.p. 147 ꢀC. [1H]-NMR (CDCl3) d: 2.95
(s, 3H, CH3), 3.61 (s, 4H, CH2CH2), 3.76 (s, 3H, OCH3), 4.59 (s, 2H,
CH2), 6.77 (d, J ¼ 6.4 Hz, 1H, NH), 7.06–7.66 (m, 4H, Ar), 8.31 (s, 1H,
NH) ppm. [13C]-NMR (CDCl3) d: 33.70 (CH3), 41.32 (CH2), 46.20
(CH2), 50.22 (CH2), 55.68 (OCH3), 113.67 (CHAr), 114.00 (CHAr),
120.27 (CHAr), 129.96 (CHAr), 137.43 (CAr), 158.22 (CAr), 159.94
(C¼N), ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for C12H18N3Oþ
220.1444; found 220.1447.
N-(3-Fluorobenzyl)-1-methyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 18. White solid, m.p. 195 ꢀC. [1H]-NMR (CDCl3) d: 3.19
(s, 3H, CH3), 3.61–3.71 (m, 4H, CH2CH2), 4.68 (s, 2H, CH2), 6.95 (t,
J ¼ 7.7 Hz, 1H, NH), 7.09 – 7.41 (m, 4H, Ar), 8.27 (bs, 1H, NH) ppm.
[13C]-NMR (CDCl3) d: 33.86 (CH3), 41.19 (CH2), 45.42 (CH2), 50.20
(CH2), 115.05 (d, JCF¼ 25 Hz, CHAr), 123.94 (CHAr), 130.45 (d,
J ¼ 8 Hz, CHAr), 138.48 (CAr), 158.11 (C¼N), 162.78 (d, J ¼ 246 Hz,
CF) ppm.
found 204.1494.
N,1-Dimethyl-N-phenethyl-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 9. White solid; m.p. 109–110 ꢀC. [1H]-NMR (CDCl3) d:
2.82 (s, 3H, CH3); 2.97 (t, J ¼ 6.8 Hz, 2H, PhCH2); 3.13 (s, 3H, CH3);
3.55–3.62 (m, 4H, CH2CH2); 3.77 (t, J ¼ 6.9 Hz, 2H, CH2N); 7.32 (t,
J ¼ 7.5 Hz, 5H, Ar), 8.34 (bs, 1H, NH) ppm. [13C]-NMR (CDCl3) d:
33.66 (CH2); 36.97 (CH3); 39.70 (CH3); 40.33 (CH2); 52.89 (CH2);
54.71 (CH2); 127.23 (CH-Ar); 128.92 (CH-Ar); 136.96 (C-Ar); 162.4þ7
(C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for C13H20N3
218.1652; found 218.1649.
N-Benzyl-N,1-dimethyl-4,5-dihydro-1H-imidazol-2-amine hydro-
iodide 10. Purification by flash chromatography (CH2Cl2/CH3OH/
NH3 90:10:1 as eluent). Oil. [1H]-NMR (CDCl3) d: 3.01 (s, 3H, CH3);
3.07 (s, 3H, CH3); 3.70–3.87 (m, 4H, CH2CH2); 4.63 (s, 2H, CH2Ph);
7.22–7.35 (m, 5H, Ar), 8.10 (s, 1H, NH) ppm. [13C]-NMR (CDCl3) d:
37.03 (CH3); 39.72 (CH3); 40.53 (CH2); 53.14 (CH2); 56.60 (CH2);
127.20 (CHAr); 128.44 (CHAr); 129.25 (CHAr); 133.94 (CAr); 162.6þ3
(C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ: calculated for C12H18N3
204.1495; found 204.1497.
N-Benzyl-1-methyl-4,5-dihydro-1H-imidazol-2-amine hydroiodide
11. White solid; m.p. 130–133 ꢀC. [1H]-NMR (CDCl3) d: 3.16 (s, 3H,
CH3); 3.58–3.66 (m, 4H, CH2CH2); 4.67 (d, J ¼ 5.6 Hz, 2H, CH2Ph);
6.87 (s, 1H, NH); 7.25–7.38 (m, 3H, Ar); 7.49 (d, J ¼ 7.2 Hz, 2H, Ar);
8.21 (s, 1H, NH) ppm. [13C]-NMR (CDCl3) d: 33.76 (CH3); 41.31
(CH2); 46.38 (CH2); 50.22 (CH2); 128.13 (CHAr); 128.34 (CHAr); 129.04
(CHAr); 135.63 (CAr); 158.35 (C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ:
N1-Benzyl-N2-(4,5-dihydro-1H-imidazol-2-yl)ethane-1,2-diamine
hydroiodide 19. White solid, m.p. 230 ꢀC (dec). [1H]-NMR (MeOD)
d: 3.37 (t, J ¼ 6.2 Hz, 2H, CH2), 3.64 (t, J ¼ 6.2 Hz, 2H, CH2), 3.70 (s,
4H, CH2CH2), 4.34 (s, 2H, PhCH2), 7.40–7.47 (m, 3H, Ar), 7.59–7.64
(m, 2H, Ar) ppm. [13C]-NMR (MeOD) d: 38.87 (CH3), 42.82 (CH2CH2),
45.73 (CH2), 51.20 (PhCH2), 128.92 (CHAr), 129.49 (CHAr), 129.99
(CHAr), 130.69 (CAr), 159.88 (C¼N) ppm. ESI-HRMS (m/z) [M þ H]þ:
þ
calculated for C11H16N3 190.1339; found 190.1338.
1-Methyl-N-(3-phenylpropyl)-4,5-dihydro-1H-imidazol-2-amine
hydroiodide 12. Purification by flash chromatography (CH2Cl2/
CH3OH/NH3 90:10:1 as eluent). Gum. [1H]-NMR (CDCl3) d: 2.02 (p,
J ¼ 7.6 Hz, 2H); 2.69 (t, J ¼ 8.0 Hz, 2H, CH2); 2.97 (s, 3H, CH3);
3.41–3.54 (m, 4H, CH2CH2); 3.60 (t, J ¼ 8.0 Hz, 2H, CH2); 7.10–7.25
(m, 5H, Ar) ppm. [13C]-NMR (CDCl3) d: 30.62 (CH2), 32.93 (CH2),
33.77 (NCH3), 40.97 (CH2), 43.83 (CH2), 50.11 (CH2), 126.01 (CHAr),
þ
calculated for C12H19N4 219.1604; found 219.1606.
N1-Benzyl-N2-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)ethane-1,2-
diamine hydroiodide 20. White solid, m.p. 235 ꢀC (dec). [1H]-NMR
128.44 (CHAr), 128.58 (CHAr), 141.25 (CAr), 157.91 (C¼N) ppm. ESI- (MeOD) d: 2.93 (s, 3H, CH3), 3.33 (t, J ¼ 6.0 Hz, 2H, CH2), 3.63–3.72