1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 2H), 4.4–3.8 (bs, 6H
+ H2O), 2.08 (t, J = 7.2 Hz, 2H), 1.48 (p, J = 7.2 Hz, 2H), 1.23
(bs, 8H), 0.84 (t, J = 6.8 Hz, 3H) ppm. 13C NMR (100 MHz,
DMSO-d6) δ 172.0, 159.5, 158.3, 105.9, 90.7, 75.1, 35.1, 31.3,
28.7, 28.6, 28.5, 25.2, 22.1, 14.0 ppm; IR νmax (cm−1) 3296,
3168, 2921, 2850, 1693, 1643, 1602, 1533, 1504, 1467, 1413,
1396, 1348, 1300, 661; HRMS (ESI) calcd for C15H22N4O (M+)
275.1866, found 275.1868.
N-(3-(2-Aminopyrimidin-5-yl)propyl)octanamide
hydrochloride (14)
Following the general Boc-deprotection procedure di-tert-butyl
5-(3-octanamidopropyl)pyrimidin-2-ylcarbamate was reacted to
give N-(3-(2-aminopyrimidin-5-yl)propyl)octanamide hydro-
1
chloride (0.05 g, 99%) as a tan solid (m.p. = 140–142 °C). H
NMR (400 MHz, CD3OD) δ 8.50 (s, 2H), 3.24 (t, J = 6.8 Hz,
2H), 2.62 (t, J = 8 Hz, 2H), 2.25 (t, 8 Hz, 2H), 1.83 (p, J = 8
Hz, 2H), 1.62 (p, J = 8 Hz, 2H), 1.33–1.31 (m, 8H), 0.90 (t, J =
8 Hz, 3H) ppm; 13C NMR (100 MHz, CD3OD) δ 177.6, 157.7,
156.5, 125.0, 40.1, 36.5, 32.9, 30.5, 30.3, 30.1, 27.3, 27.0, 23.7,
14.5 ppm; IR νmax (cm−1) 3303, 3156, 2922, 2850, 1701, 1658,
1636, 1539, 1467, 1395; HRMS (ESI) calcd for C15H26N4O
(M+) 279.2179, found 279.2181.
N-(3-(2-Aminopyrimidin-5-yl)prop-2-ynyl)decanamide
hydrochloride (11)
Following the general Boc-deprotection procedure di-tert-butyl
5-(3-decanamidoprop-1-ynyl)pyrimidin-2-ylcarbamate was reacted
to give N-(3-(2-aminopyrimidin-5-yl)prop-2-ynyl)decanamide
hydrochloride (0.04 g, 99%) as a tan solid (m.p. = 154–156 °C).
1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 2H), 4.66 (bs, 4H),
4.30 (d, J = 5.2 Hz, 2H), 2.08 (t, J = 7.6 Hz, 2H), 1.48 (m, 2H),
1.22 (m, 12H), 0.84 (t, J = 6.8 Hz, 3H) ppm; 13C NMR
(100 MHz, DMSO-d6) δ 172.0, 159.8, 159.7, 105.9, 90.2, 75.8,
35.1, 31.3, 29.0, 28.8, 28.7, 28.7, 28.5, 25.2, 22.1, 14.0 ppm; IR
νmax (cm−1) 3295, 2921, 2850, 1693, 1643, 1533, 1467, 1396,
1348, 1226, 1195, 661; HRMS (ESI) calcd for C17H26N4O (M+)
303.2179, found 303.2179.
N-(3-(2-Aminopyrimidin-5-yl)propyl)decanamide
hydrochloride (15)
Following the general Boc-deprotection procedure di-tert-butyl
5-(3-decanamidopropyl)pyrimidin-2-ylcarbamate was reacted to
give N-(3-(2-aminopyrimidin-5-yl)propyl)decanamide hydro-
1
chloride (0.03 g, 99%) as a tan solid (m.p. = 144–148 °C). H
NMR (400 MHz, CD3OD) δ 8.49 (s, 2H), 3.20 (t, J = 6.4 Hz,
2H), 2.60 (t, J = 8 Hz, 2H), 2.19 (t, J = 8 Hz, 2H), 1.81 (p, J =
8 Hz, 2H), 1.60 (p, J = 8 Hz, 2H), 1.32–1.29 (m, 12H), 0.89
(t, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz, CD3OD) δ 175.3,
156.4, 155.4, 123.8, 37.8, 36.0, 31.9, 29.8, 29.4, 29.3, 29.2,
29.2, 25.9, 25.7, 22.6, 13.3 ppm; IR νmax (cm−1) 3303, 3158,
2921, 2850, 1702, 1658, 1637, 1538, 1467, 1396, 1211; HRMS
(ESI) calcd for C17H30N4O (M+) 307.2492, found 307.2498.
N-(3-(2-Aminopyrimidin-5-yl)prop-2-ynyl)dodecanamide
hydrochloride (12)
Following the general Boc-deprotection procedure di-tert-butyl
5-(3-dodecanamidoprop-1-ynyl)pyrimidin-2-ylcarbamate
was
reacted to give N-(3-(2-aminopyrimidin-5-yl)prop-2-ynyl)
dodecanamide hydrochloride (0.04 g, 99%) as a tan solid (m.
p. = 154–156 °C). 1H NMR (300 MHz, DMSO-d6) δ 8.38
(s, 2H), 4.49 (bs, 4H), 4.08 (d, J = 5.7 Hz, 2H), 2.08 (t, J = 7.2
Hz, 2H), 1.48 (p, J = 6.9 Hz, 2H), 1.22 (s, 12H), 0.84 (t, J = 6.3
Hz, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ 172.0, 160.2,
160.0 105.9, 90.0, 76.0, 35.1, 31.3, 29.1, 29.0, 28.8, 28.8, 28.7,
28.6, 25.2, 22.1, 14.1 ppm; IR νmax (cm−1) 3297, 3176, 2919,
2850, 1693, 1641, 1602, 1553, 1504, 1467, 1415, 661; HRMS
(ESI) calcd for C19H30N4O (M+) 331.2492, found 331.2943.
N-(3-(2-Aminopyrimidin-5-yl)propyl)dodecanamide
hydrochloride (16)
Following the general Boc-deprotection procedure di-tert-butyl
5-(3-dodecanamidopropyl)pyrimidin-2-ylcarbamate was reacted
to give N-(3-(2-aminopyrimidin-5-yl)propyl)dodecanamide
hydrochloride (0.04 g, 99%) as a tan solid (m.p. = 145–147 °C).
1H NMR (400 MHz, CD3OD) δ 8.50 (s, 2H), 3.21 (t, J = 8 Hz,
2H), 2.61 (t, J = 8 Hz, 2H), 2.20 (t, J = 8 Hz, 2H), 1.81 (p, J =
8 Hz, 2H), 1.61 (p, J = 8 Hz, 2H), 1.32–1.29 (m, 16H), 0.90
(t, J = 6.8 Hz, 3H) ppm; 13C NMR (75 MHz, DMSO-d6) δ
172.2, 156.5, 155.3, 122.9, 37.2, 35.4, 31.3, 29.8, 29.0, 29.0,
28.8, 28.8, 25.3, 22.1, 14.0 ppm; IR νmax (cm−1) 3301, 3159,
2925, 2855, 1704, 1659, 1632, 1535, 1467, 1391; HRMS (ESI)
calcd for C19H34N4O (M+) 335.2805, found 335.2805.
N-(3-(2-Aminopyrimidin-5-yl)propyl)hexanamide
hydrochloride (13)
Following the general Boc-deprotection procedure di-tert-butyl
5-(3-hexanamidopropyl)pyrimidin-2-ylcarbamate was reacted to
give N-(3-(2-aminopyrimidin-5-yl)propyl)hexanamide hydro-
chloride (.04, 99%) as a tan solid (m.p. = 138–142 °C). 1H
NMR (400 MHz, CD3OD) δ 8.54 (s, 2H), 3.34 (m, 2H), 2.65
(t, J = 8 Hz, 2H), 2.375 (t, J = 7.2 Hz, 2H), 1.88 (p, J = 7.2 Hz,
2H), 1.65 (p, J = 8 Hz), 1.39–1.30 (m, 4H), 0.92 (t, J = 7.6 Hz,
3H) ppm; 13C NMR (100 MHz, CD3OD) δ 178.5, 157.7, 156.5,
124.8, 40.9, 35.8, 32.5, 30.2, 27.0, 26.9, 23.4, 14.4 ppm; IR
νmax (cm−1) 3303, 3158, 2921, 2850, 1702, 1658, 1637, 1538,
1467, 1396; HRMS (ESI) calcd for C13H22N4O (M+) 251.1866,
found 251.1869.
5-Ethynylpyrimidin-2-amine (17)
Was synthesized following the general procedure by H. Zhao
et al.33
General procedure for click reactions
The terminal alkyne (1.0 mmol.) was dissolved in
1 : 1 : 1 mixture of tert-butanol, water and methylene chloride
(ca. 3 mL per 0.200 g of terminal alkyne). To this mixture, the
a
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Org. Biomol. Chem., 2012, 10, 2552–2561 | 2557