de Greef et al.
JOCArticle
Currently, we are investigating the influence of other side
chains containing hydrogen bond acceptors and donors on
the UPy dimerization strength to show the generality of the
results as displayed in this paper.
resulted in pure 1c as a white powder (0.37 g, 0.85 mmol), mp
1
92.7-93.1 °C. Yield: 78%. H NMR (CDCl
NH), 11.94 (s, 1H, NH), 10.27 (s, 1H, NH), 5.80 (s, 1H, Od
3
): δ 13.08 (s, 1H,
C-CHdC-CH ), 3.67-3.64 (m, 4H, O-CH -), 3.54 (m, 2H,
2
2
O-CH -), 3.47 (m, 2H, NH-CH
2
2
-CH
2 3
-O), 3.37 (s, 3H, O-CH ),
2
CH
(CDCl
.45 (t, 2H, CHdC-CH
2
-CH
), 1.32-1.26 (m, 20H, -CH
): δ 173.0, 156.8, 154.6, 152.4, 105.8, 72.0, 70.5, 70.3,
2
), 1.62 (m, 2H, CHdC-CH
2 3
-), 0.88 (t, 3H, -CH ). C NMR
2
-CH
2
-
Experimental Section
13
2
Synthesis of 2-(2-Methoxyethyl)-ureido-6-tridecyl-4[1H]pyri-
midinone (1a). Activated pyrimidinone 3 (1.94 g, 5.00 mmol) and
3
69.4, 59.0, 39.5, 32.7, 31.9, 29.6-28.8 (multiple signals), 27.0,
22.7, 14.1. IR (ATR): ν = 2919, 2852, 1698, 1664, 1620, 1585,
1563, 1527, 1489, 1468, 1456, 1398, 1332, 1302, 1261, 1202, 1124,
2
-methoxyethyl amine 2a (0.75 g, 10.00 mmol) were added to dry
CHCl
(16 mL) and stirred at 60 °C for 2 days. After cooling to
room temperature, 50 mL of CHCl was added, and the mixture
3
-1
1029, 983, 947, 884, 854, 808, 771, 744, 722 cm . MALDI-TOF-
3
þ
þ
was extracted 3 times with 15 mL of aqueous 1 M HCl,
neutralized with 20 mL of saturated NaHCO (aq), and washed
with 20 mL of brine. After drying with MgSO the solvent was
4
MS (m/z): 438.32, obsd 439.37 (MH ), 461.62 (MNa ). Anal.
Calcd for C23 : C 62.98, H 9.65, N 12.77. Found: C
62.87, H 9.79, N 12.76.
42 4 4
H N O
3
removed by evaporation in vacuo, resulting in the crude ureido-
pyrimidinone (1.66 g, 4.2 mmol). Further purification by silica
Synthesis of 2-[3-(2-Methoxyethoxy)propyl]ureido-6-tridecyl-
4[1H]pyrimidinone (1d). Activated pyrimidinone 3 (1.55 g,
4.0 mmol) and 3-(2-methoxyethoxy)propyl amine 2d (0.955 g,
filtration using 4% methanol in CHCl
3
as eluent resulted in pure
1
Yield: 71%. H NMR (CDCl
a as a white powder (1.40 g, 3.5 mmol), mp 118.5-119.8 °C.
7.2 mmol) were added to dry CHCl
for 2 days. After cooling to room temperature, 150 mL of CHCl
3
(15 mL) and stirred at 60 °C
1
3
): δ 13.09 (s, 1H, NH), 11.95 (s, 1H
3
NH), 10.33 (s, 1H, NH), 5.82 (s, 1H, OdC-CHdC-CH ), 3.56
was added, and the mixture was extracted 3 times with 60 mL of
aqueous 0.1 M HCl (aq), neutralized with 150 mL of saturated
2
(
m, 2H, NH-CH
O), 3.38 (s, 3H, O-CH
H, CHdC-CH -CH
2
-CH
2
-O), 3.48 (t, 2H, m, 2H, NH-CH
), 2.45 (t, 2H, CHdC-CH -CH ), 1.62 (m,
-CH ), 1.31-1.25 (m, 20H, -CH -), 0.87
t, 3H, -CH3). C NMR (CDCl ): δ 173.1, 156.9, 154.6, 152.4,
2 2
-CH -
NaHCO
with MgSO
(aq), and washed with 150 mL of brine. After drying
the solvent was removed by evaporation in vacuo,
3
2
2
3
2
(
2
2
2
2
4
13
resulting in the crude ureido-pyrimidinone (1.53 g, 3.4 mmol).
Further purification by recrystallization from 2-propanol, re-
sulted in pure 1d as a white powder (0.958 g, 2.1 mmol), mp
3
1
2
1
9
05.9, 71.0, 58.8, 39.6, 32.7, 31.9, 29.6-28.8 (multiple signals),
7.0, 22.7, 14.1. IR (ATR): ν = 2953, 2918, 2850, 1698, 1660,
582, 1524, 1467, 1438, 1310, 1258, 1212, 1199, 1137, 1124, 1088,
1
92.9-93.4 °C Yield: 53%. H NMR (CDCl
NH), 11.90 (s, 1H, NH), 10.21 (s, 1H, NH), 5.79 (s, 1H, OdC-
3
): δ 13.14 (s, 1H,
-
1
65, 943, 884, 810, 771, 743, 721 cm . MALDI-TOF-MS (m/z):
þ
þ
calcd 394.29, obsd 395.26 (MH ), 417.24 (MNa ). Anal. Calcd
for C21 : C 63.93, H 9.71, N 14.20. Found: C 64.12, H
.94, N 14.45.
Synthesis of 2-(3-Methoxypropyl)-ureido-6-tridecyl-4[1H]pyri-
midinone (1b). Activated pyrimidinone 3 (1.94 g, 5.00 mmol) and
-methoxypropyl amine 2b (0.89 g, 10.00 mmol) were added to dry
CHCl (16 mL) and stirred at 60 °C for 2 days. After cooling to
CHdC-CH
3.36 (m, 2H, NH-CH
1.91 (m, 2H, NH-CH -CH
CH -CH ), 1.32-1.21 (m, 20H, -CH
NMR (CDCl
2
), 3.60-3.52 (m, 6H, O-CH
-CH ), 2.46 (t, 2H, CHdC-CH
-CH
2
-), 3.38 (s, 3H, O-CH
3
),
),
H
38
N
4
O
3
2
2
2
-CH
2
9
2
2
2
-O), 1.63 (m, 2H, CHdC-CH
2
-
1
3
2
2
2
3
-), 0.88 (t, 3H, -CH ). C
): δ 173.0, 156.7, 154.7, 152.4, 105.8, 72.0, 70.1,
3
3
68.9, 59.0, 37.1, 32.7, 31.9, 29.6-28.8 (multiple signals), 27.0,
22.7, 14.1. IR (ATR): ν = 2955, 2921, 2852, 1698, 1662, 1585,
1527, 1469, 1446, 1309, 1258, 1200, 1136, 1112, 1047, 947, 882,
3
3
room temperature, 50 mL of CHCl was added, and the mixture
-
1
was extracted 3 times with 15 mL of 1 M aqueous HCl, neutralized
with 20 mL of saturated NaHCO (aq), and washed with 20 mL of
849, 815, 792, 771, 742 cm . MALDI-TOF-MS (m/z): 452.33,
obsd 453.38 (MH ), 475.36 (MNa ). Anal. Calcd for
24 44 4 4
C H N O : C 63.68, H 9.80, N 12.38. Found: C 63.83, H
þ
þ
3
brine. After drying with MgSO the solvent was removed by
4
evaporation in vacuo, resulting in the crude ureidopyrimidinone
(1.90 g, 4.65 mmol). Further purification by silica filtration using
9.94, N 12.46.
Synthesis of 2-{2-[2-(2-Methoxyethoxy)ethoxy]ethyl}ureido-
6-tridecyl-4[1H] pyrimidinone (1e). Activated pyrimidinone 3
(1.04 g, 2.68 mmol) and 2-(2-[2-methoxyethoxy]ethoxy)ethyl
amine 2e (0.889 g, 5.45 mmol) were added to dry CHCl
(9 mL) and stirred at 60 °C for 2 days. After cooling to room
temperature, 25 mL of CHCl was added, and the mixture was
extracted 3 times with 10 mL of 0.1 M aqueous HCl, neutralized
with 15 mL of saturated NaHCO (aq), and washed with 20 mL
of brine. After drying with MgSO the solvent was removed by
4% methanol in CHCl as eluent resulted in the pure product as a
3
white powder (1.61 g, 3.95 mmol), mp 89.3-89.9 °C. Yield: 79%.
1
H NMR (CDCl
s, 1H, NH), 5.81 (s, 1H, OdC-CHdC-CH
CH -O), 3.35-3.32 (m, 5H, NH-CH -CH and O-CH ), 2.45 (t,
3
): δ 13.15 (s, 1H, NH), 11.91 (s, 1H, NH), 10.22
3
(
2
), 3.45 (t, 2H, CH
2
-
2
2
2
3
3
2
H, CHdC-CH
2
-CH
-CH
). C NMR (CDCl
2
), 1.88 (m, 2H, NH-CH
-CH ), 1.31-1.25 (m, 20H, -CH
): δ 173.1, 156.7, 154.7, 152.4,
2
-CH
2
-CH
2
-O), 1.62
(
(
m, 2H, CHdC-CH
t, 3H, -CH
2
2
2
2
-), 0.87
3
13
3
3
4
1
2
1
7
05.8, 70.1, 58.6, 37.0, 32.7, 31.9, 29.6-28.8 (multiple signals),
7.0, 22.6, 14.1. IR (ATR): ν = 2918, 2850, 1698, 1657, 1579, 1524,
467, 1445, 1395, 1307, 1255, 1212, 1196, 1126, 1109, 946, 884, 813,
evaporation in vacuo, resulting in the crude ureidopyrimidinone
(1.1 g, 2.3 mmol). Further purification by recrystallization from
2-propanol, resulted in pure 1e as a white powder (0.89 g,
-
1
1
92, 771, 741, 722 cm . MALDI-TOF-MS (m/z): calcd 408.31,
1.8 mmol), mp 82.6-83.0 °C. Yield: 69%. H NMR (CDCl
3
):
þ
þ
obsd 409.42 (MH ), 431.40 (MNa ). Anal. Calcd for
: C 64.67, H 9.87, N 13.71. Found: C 65.10, H 9.97,
N 13.85.
δ 13.08 (s, 1H, NH), 11.93 (s, 1H, NH), 10.28 (s, 1H, NH), 5.80
(s, 1H, OdC-CHdC-CH ), 3.64 (m, 8H, O-CH -), 3.52-3.47
(m, 4H, O-CH -), 3.35 (s, 3H, O-CH ), 2.45 (t, 2H,
CHdC-CH -CH ), 1.63 (m, 2H, CHdC-CH -CH -CH ), 1.28
(m, 20H, -CH ). C NMR (CDCl ): δ 173.0,
C
22
H
40
N
4
O
3
2
2
2
- þ NH-CH
2
3
Synthesis of 2-[2-(2-Methoxyethoxy)ethyl]ureido-6-tridecyl-4-
1H]pyrimidinone (1c). Activated pyrimidinone 3 (0.428 g, 1.1
2
2
2
2
2
1
3
[
2
-), 0.87 (t, 3H, -CH
3
3
mmol) and 2-(2-methoxyethoxy)ethyl amine 2c (0.20 g, 1.6
mmol) were added to dry CHCl
for 2 days. After cooling to room temperature, 50 mL of CHCl3
was added, and the mixture was extracted 3 times with 15 mL of
156.8, 154.6, 152.4, 105.8, 72.0, 70.5, 70.3, 69.4, 59.0, 39.5, 32.7,
31.9, 29.6-28.8 (multiple signals), 27.0, 22.7, 14.1. IR (ATR):
ν = 3216, 3135, 3030, 2955, 2918, 2873, 2853, 2817, 1702, 1676,
1641, 1620, 1594, 1562, 1470, 1456, 1418, 1400, 1333, 1280, 1262,
1202, 1186, 1122, 1045, 1028, 997, 982, 949, 937, 925, 866, 854,
3
(4 mL) and stirred at 60 °C
1
M aqueous HCl, neutralized with 20 mL of saturated NaH-
CO (aq), and washed with 20 mL of brine. After drying with
-1
827, 799, 791, 780, 772, 767, 742, 720, 708, 694 cm . MALDI-
TOF-MS (m/z): 482.35, obsd 483.37 (MH ), 505.34 (MNa ).
3
þ
þ
MgSO4 the solvent was removed by evaporation in vacuo,
resulting in the crude ureidopyrimidinone (0.44 g, 1.0 mmol).
Further purification by recrystallization from 2-propanol,
Anal. Calcd for C H N O : C 62.21, H 9.61, N 11.61. Found:
4
2
5
46
5
C 62.51, H 9.69, N 11.70.
6
08 J. Org. Chem. Vol. 75, No. 3, 2010