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3-(5-Amino-1H-1,2,4-triazol-3-yl)-1-(piperidin-1-yl)propan-1-one
RSC Advances
CH2CH2C]O), 4.25 (2H, d, 3J ¼ 5.9 Hz, CH2NH), 5.07–5.76 (2H,
br s, NH2), 7.05–7.09 (1H, m, H-20), 7.23–7.40 (2H, m, H-50 and
H-60), 8.42 (1H, br t, 3J ¼ 5.6 Hz, NHC]O), 11.58–12.30 (1H, br s,
NH). 13C NMR (75 MHz, DMSO-d6): d 24.0 (CH2CH2C]O), 33.3
(5b). White solid, yield (1 mmol/10 mmol scale): 180 mg (81%)/
1.62 g (73%), mp 165–167 ꢀC (MeCN). 1H NMR (300 MHz, DMSO-
d6): d 1.42–1.60 (6H, m, (CH2)3), 2.62 (4H, s, (CH2)2C]O), 3.36–
3.42 (4H, m, (CH2)2N), 5.53 (2H, br s, NH2), 11.69 (1H, br s, NH).
13C NMR (75 MHz, DMSO-d6): d 23.2 (CH2CH2C]O), 24.0 (CH2),
25.2 (CH2), 25.9 (CH2), 30.4 (CH2CH2C]O), 41.9 (CH2N), 45.7
(CH2N), 158.5 (C-3 and C-5), 169.2 (C]O). IR (KBr) n 3305 (N–H),
3138 (N–H), 1617 (C]O), 1479, 1405, 1287, 1135, 1098,
1067 cmꢁ1. Anal. calcd for C10H17N5O: C, 53.79; H, 7.67; N, 31.37.
Found: C, 53.67; H, 7.72; N, 31.24.
2
(CH2CH2C]O), 41.0 (CH2NH), 115.9 (d, JCF ¼ 17.4 Hz, C-20),
2
4
3
117.1 (d, JCF ¼ 17.0 Hz, C-50), 123.6 (dd, JCF ] 3.1 Hz, JCF
¼
7.0 Hz, C-60), 137.5 (dd, 4JCF ¼ 3.8 Hz, 3JCF ¼ 5.5 Hz, C-10), 148.2
2
1
2
(dd, JCF ¼ 12.5 Hz, JCF ¼ 243.8 Hz, C-40), 149.1 (dd, JCF
¼
1
12.7 Hz, JCF ¼ 245.1 Hz, C-30), 156.7 and 159.8 (C-3 and C-5),
171.4 (C]O). IR (KBr) n 3417 (N–H), 3322 (N–H), 3246 (N–H),
1636 (C]O), 1554, 1433, 1226, 1115, 1061, 1014 cmꢁ1. Anal.
calcd for C12H13F2N5O: C, 51.24; H, 4.66; N, 24.90. Found: C,
51.09; H, 4.72; N, 24.78.
3-(5-Amino-1H-1,2,4-triazol-3-yl)-N-(4-benzyl)propanamide (5d).
White solid, yield (1 mmol/10 mmol scale): 191 mg (78%)/2.05 g
(84%), mp 208–210 ꢀC (EtOH). 1H NMR (300 MHz, DMSO-d6):
d 2.45–2.49 (2H, m, CH2CH2C]O), 2.67 (2H, t, 3J ¼ 7.7 Hz,
3-(5-Amino-1H-1,2,4-triazol-3-yl)-N-(3-triuoromethylbenzyl)
propanamide (5h). White solid, yield: 181 mg (58%), mp 157–
158 C (EtOH). H NMR (300 MHz, DMSO-d6): d 2.48–2.71 (4H,
1
3
ꢀ
CH2CH2C]O), 4.26 (2H, d, J ¼ 5.9 Hz, CH2NH), 5.61 (2H, br s,
3
NH2), 7.21–7.33 (5H, m, H-20, H-30, H-40, H-50and H-60), 8.35 (1H, br
t, 3J ¼ 5.6 Hz, NHC]O), 11.67 (1H, br s, NH). 13C NMR (75 MHz,
DMSO-d6): d 23.6 (CH2CH2C]O), 33.4 (CH2CH2C]O), 41.9
(CH2NH), 126.5 (C-40), 127.0 (C-20 and C-60), 128.1 (C-30 and C-50),
139.5 (C-10), 158.3 (C-3 and C-5), 171.2 (C]O). IR (KBr) n 3414 (N–
H), 3324 (N–H), 3247 (N–H), 1638 (C]O), 1546, 1482, 1225, 1081,
1058, 1003 cmꢁ1. Anal. calcd for C12H15N5O: C, 58.76; H, 6.16; N,
28.55. Found: C, 58.61; H, 6.30; N, 28.47.
m, CH2CH2C]O), 4.36 (2H, d, J ¼ 5.9 Hz, CH2NH), 5.11–5.74
(2H, br s, NH2), 7.54–7.59 (4H, m, H-20, H-30, H-50 and H-60), 8.49
(1H, br t, 3J ¼ 5.5 Hz, NHC]O), 11.60–12.30 (1H, br s, NH). 13
C
NMR (75 MHz, DMSO-d6):
d 23.9 (CH2CH2C]O), 33.4
3
(CH2CH2C]O), 41.5 (CH2NH), 123.3 (q, JCF ¼ 3.7 Hz, C-40),
3
1
123.5 (q, JCF ¼ 3.8 Hz, C-20), 124.2 (q, JCF ¼ 272.2 Hz, CF3),
128.9 (q, 2JCF ¼ 31.4 Hz, C-30), 129.3 (C-50), 131.2 (C-60), 141.1 (C-
10), 156.8 and 159.8 (C-3 and C-5), 171.5 (C]O). IR (KBr) n 3410
(N–H), 3321 (N–H), 3232 (N–H), 1641 (C]O), 1553, 1480, 1260,
1167, 1115, 1071 cmꢁ1. Anal. calcd for C13H14F3N5O: C, 49.84;
H, 4.50; N, 22.36. Found: C, 49.79; H, 4.53; N, 22.29.
3-(5-Amino-1H-1,2,4-triazol-3-yl)-N-(4-methoxybenzyl)prop-
anamide (5e). White solid, yield: 224 mg (84%), mp 218–
220 ꢀC (EtOH). 1H NMR (300 MHz, DMSO-d6): d 2.38–2.48 (2H,
m, CH2CH2C]O), 2.65 (2H, t, 3J ¼ 7.7 Hz, CH2CH2C]O), 3.72
(3H, s, OCH3), 4.19 (2H, d, 3J ¼ 5.9 Hz, CH2NH), 5.62 (2H, br s,
NH2), 6.87 (2H, d, 3J ¼ 8.7 Hz, H-30 and H-50), 7.15 (2H, d, 3J ¼
3-(5-Amino-1H-1,2,4-triazol-3-yl)-N-(phenethyl)propanamide
(5i). White solid, yield (1 mmol/10 mmol scale): 211 mg (81%)/
2.13 g (82%), mp 188–190 ꢀC (EtOH). 1H NMR (300 MHz, DMSO-
3
3
3
8.7 Hz, H-20 and H-60), 8.27 (1H, br t, J ¼ 5.7 Hz, NHC]O),
d6): d 2.37 (2H, t, J ¼ 7.9 Hz, CH2CH2C]O), 2.60 (2H, t, J ¼
7.8 Hz, CH2CH2C]O), 2.69 (2H, t, 3J ¼ 7.4 Hz, CH2CH2NH), 3.25
(2H, q, 3 J ¼ 6.8 Hz, CH2CH2NH), 5.59 (2H, br s, NH2), 7.17–7.31
(5H, m, H-20, H-30, H-40, H-50and H-60), 7.94 (1H, br t, 3J ¼ 5.4 Hz,
NHC]O), 11.68 (1H, br s, NH). 13C NMR (75 MHz, DMSO-d6):
d 23.6 (CH2CH2C]O), 33.4 (CH2CH2C]O), 35.1 (CH2CH2NH),
40.1 (CH2CH2NH), 125.9 (C-40), 128.2 (C-20 and C-60), 128.5 (C-30
and C-50), 139.4 (C-10), 158.5 (C-3 and C-5), 171.0 (C]O). IR
(KBr) n 3417 (N–H), 3325 (N–H), 3241 (N–H), 1640 (C]O), 1553,
1479, 1227, 1085, 1063, 1018 cmꢁ1. Anal. calcd for C14H17N5O:
C, 60.21; H, 6.61; N, 27.01. Found: C, 60.08; H, 6.70; N, 26.88.
11.64 (1H, br s, NH). 13C NMR (75 MHz, DMSO-d6): d 23.6
(CH2CH2C]O), 33.4 (CH2CH2C]O), 41.3 (CH2NH), 54.9
(OCH3), 113.6 (C-30 and C-50), 128.3 (C-20 and C-60), 131.4 (C-10),
158.0 (C-40), 159.5 (C-3 and C-5), 171.0 (C]O). IR (KBr) n 3413
(N–H), 3324 (N–H), 3246 (N–H), 1637 (C]O), 1547, 1482, 1257,
1106, 1058, 1032 cmꢁ1. Anal. calcd for C13H17N5O2: C, 56.71;
H, 6.22; N, 25.44. Found: C, 56.58; H, 6.31; N, 25.32.
3-(5-Amino-1H-1,2,4-triazol-3-yl)-N-(4-uorobenzyl)prop-
anamide (5f). White solid, yield: 199 mg (76%), mp 218–219 ꢀC
(EtOH). 1H NMR (300 MHz, DMSO-d6): d 2.41–2.51 (2H, m,
CH2CH2C]O), 2.67 (2H, t, 3J ¼ 7.6 Hz, CH2CH2C]O), 4.24 (2H,
d, 3J ¼ 5.9 Hz, CH2NH), 5.61 (2H, br s, NH2), 7.12 (2H, dd, 3JHH
¼
Microwave-assisted synthesis of 3-(5-amino-1H-1,2,4-triazol-3-
8.9 Hz, 3JHF ¼ 8.9 Hz, H-30 and H-50), 7.25 (2H, dd, 4JHF ¼ 5.7 Hz,
3JHH ¼ 8.8 Hz, H-20 and H-60), 8.36 (1H, br t, 3J ¼ 5.8 Hz, NHC]
O), 11.69 (1H, br s, NH). 13C NMR (75 MHz, DMSO-d6): d 23.6
(CH2CH2C]O), 33.4 (CH2CH2C]O), 41.2 (CH2NH), 114.8 (d,
2JCF ¼ 21.6 Hz, C-30 and C-50), 128.9 (d, 3JCF ¼ 8.20 Hz, C-20 and
C-60), 135.7 (d, 4JCF ¼ 3.0 Hz, C-10), 157.4 (C-3 and C-5), 161.0 (d,
1JCF ¼ 242.0 Hz, C-40), 171.2 (C]O). IR (KBr) n 3415 (N–H), 3325
(N–H), 3248 (N–H), 1639 (C]O), 1547, 1482, 1225, 1094, 1059,
1005 cmꢁ1. Anal. calcd for C12H14FN5O: C, 54.75; H, 5.36; N,
26.60. Found: 54.68; H, 5.40; N, 26.54.
yl)-1-(pyrrolidin-1-yl)propan-1-one (5c)
A mixture of N-guanidinosuccinimide (2) (156 mg, 1 mmol) and
pyrrolidine (165 mL, 2 mmol) in acetonitrile (1 mL) were irra-
diated in 10 mL seamless pressure vial using microwave system
ꢀ
operating at maximal microwave power up to 300 W at 170 C
for 25 min. Aer cooling, the solvent was evaporated under
vacuum and the residue was triturated with ethyl acetate. The
precipitate formed, was ltered, washed with ethyl acetate and
recrystalised from ethanol to give desired product 5c. White
solid; yield: 178 mg (85%); mp 189–191 ꢀC (EtOH); 1H NMR (300
MHz, DMSO-d6): d 1.75 (2H, m, 3J ¼ 6.6 Hz, CH2), 1.86 (2H, m, 3J
¼ 6.7 Hz, CH2), 2.53–2.64 (4H, m, (CH2)2C]O), 3.27 (2H, t, 3J ¼
3-(5-Amino-1H-1,2,4-triazol-3-yl)-N-(3,4-diuorobenzyl)prop-
anamide (5g). White solid, yield: 136 mg (48%), mp 173–175 ꢀC
(EtOH). 1H NMR (300 MHz, DMSO-d6): d 2.47–2.68 (4H, m,
3
6.8 Hz, CH2N), 3.39 (2H, t, J ¼ 6.7 Hz, CH2N), 5.62 (2H, br s,
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RSC Adv., 2018, 8, 22351–22360 | 22357