D. Rejman et al. / Tetrahedron 65 (2009) 8513–8523
8521
(m), 1623 (m, sh), 1591 (m), 1559 (s), 1542 (m, sh), 1506 (w), 1477
(m), 1388 (w, sh), 1368 (w), 1300 (m), 1235 (m, sh), 1212 (s), 1102
(m), 1066 (m), 1035 (m), 761 (m). dH (499.8 MHz, DMSO-d6) 1.25
(3H, t, J(CH3,CH2)¼7.1, CH2CH3), 1.63 (3H, d, J(CH3,6)¼1.2, 5-CH3),
3.04 (1H, ddd, Jgem¼13.3, J(10a,20)¼7.1, J(10a,1)¼4.9, H-10a), 3.25 (1H,
dt, Jgem¼10.9, J(30a,OH)¼J(30a,20)¼6.2, H-30a), 3.31–3.40 (2H, m, H-
10b and H-30b), 3.51 (1H, m, H-20), 4.05 (2H, q, J(CH2,CH3)¼7.1,
OCH2CH3), 4.61 (1H, t, J(OH,30)¼5.7, 30-OH), 4.87 (1H, d,
J(OH,20)¼5.1, 20-OH), 7.53 (1H, q, J(6,CH3)¼1.2, H-6), 8.75 (1H, bdd,
J(1,10b)¼6.0, J(1,10a)¼5.2, H-1), 9.67 (1H, br s, H-3). dC (125.7 MHz,
DMSO-d6) 9.16 (5-CH3), 15.49 (CH2CH3), 42.56 (C-10), 63.88 (C-30),
69.53 (OCH2CH3), 70.27 (C-20), 107.11 (C-5), 154.29 (C-2), 156.77 (C-
6), 169.69 (C-4). HRMS for C10H18N2O5Na (MþNa)þ calcd 269.1108,
found 269.1107.
J(50b,40)¼2.8, H-50b), 3.24 (1H, dd, Jgem¼12.2, J(20b,30)¼8.6, H-20b),
3.35 (1H, dd, Jgem¼12.9, J(50a,40)¼5.4, H-50a), 3.36 (1H, dd,
Jgem¼12.2, J(20a,30)¼8.4, H-20a), 4.48 (1H, ddd, J(40,30)¼5.7,
J(40,50)¼5.4, 2.8, H-40), 4.90 (1H, ddd, J(30,20)¼8.6, 8.4, J(30,40)¼5.7,
H-30), 5.82 (1H, d, J(5,6)¼8.0, H-5), 7.68 (1H, d, J(6,5)¼8.0, H-6). dC
(150.9 MHz, D2O) 48.60 (C-20), 55.19 (C-50), 61.16 (C-30), 72.05 (C-40),
103.60 (C-5), 147.94 (C-6), 156.38 (C-2), 170.46 (C-4). HRMS for
C8H12N3O3 (MþH)þ calcd 198.0873, found 198.0873.
4.6.30. 1-((3S,4S)-4-Hydroxypyrrolidin-3-yl)uracil (10c). The title
compound was prepared from 9c (0.4 g, 0.635 mmol) according to
general method E in 80% yield (0.1 g, 0.51 mmol) of white solid.
nmax(KBr) 3406 (m, br), 3185 (m, vbr), 1687 (vs, br), 1628 (m, sh),
1459 (m), 1420 (m), 1382 (m), 1270 (m), 1078 (w, br), 810 (w), 764
(w). dH (500.0 MHz, D2O) 2.94 (1H, dd, Jgem¼12.3, J(50b,40)¼5.2, H-
50b), 3.16 (1H, dd, Jgem¼12.7, J(20b,30)¼5.9, H-20b), 3.38 (1H, dd,
Jgem¼12.3, J(50a,40)¼5.9, H-50a), 3.51 (1H, dd, Jgem¼12.7, J(20a,30)¼8.1,
H-20a), 4.59 (1H, ddd, J(40,50)¼5.9, 5.2, J(40,30)¼2.7, H-40), 4.61 (1H,
ddd, J(30,20)¼8.1, 5.9, J(30,40)¼2.7, H-30), 5.83 (1H, d, J(5,6)¼7.9, H-5),
7.59 (1H, d, J(6,5)¼7.9, H-6). dC (125.7 MHz, D2O) 50.55 (C-20), 54.68
(C-50), 69.47 (C-30), 77.63 (C-40), 104.74 (C-5), 147.76 (C-6),156.16 (C-
2), 170.98 (C-4). HRMS for C8H12N3O3 (MþH)þ calcd 198.0873,
found 198.0868.
4.6.26. 1-(3-Ethoxy-2-methylacryloyl)-3-phenylurea (9s). The title
compound was prepared according to general method A from
compound 8j (0.118 g, 1.3 mmol) and reagent 7b in 87% yield
(0.28 g, 1.129 mmol) of white solid. nmax(KBr) 3284 (m), 3197 (w),
3142 (w), 3088 (w), 3059 (w), 2986 (w), 2937 (w), 2887 (w), 1702
(vs), 1676 (s), 1617 (m), 1605 (s, sh), 1592 (vs), 1557 (s), 1541 (s, sh),
1501 (m), 1488 (m, sh), 1475 (m), 1455 (s), 1396 (m), 1388 (m, sh),
1312 (w), 1226 (s, sh), 1210 (vs), 1179 (w), 1155 (w, sh), 1037 (m),
1002 (w, sh), 916 (m), 848 (vw), 757 (s), 690 (m), 618 (vw), 513 (w).
dH (499.8 MHz, CDCl3) 1.29 (3H, t, J(CH3,CH2)¼7.1, CH2CH3), 1.84
(3H, d, J(CH3,6)¼1.2, 5-CH3), 4.02 (2H, q, J(CH2,CH3)¼7.1, OCH2CH3),
7.10 (1H, m, H-40), 7.32 (2H, m, H-30), 7.50 (1H, q, J(6,CH3)¼1.2, H-6),
7.52 (2H, m, H-20), 8.53 (1H, br s, H-3), 10.97 (1H, br s, H-1). dC
(125.7 MHz, CDCl3) 8.87 (5-CH3), 15.33 (CH2CH3), 70.37 (OCH2CH3),
106.78 (C-5), 120.55 (C-20), 124.13 (C-40), 128.91 (C-30), 137.40 (C-10),
152.00 (C-2), 157.83 (C-6), 169.87 (C-4). HRMS for C13H16N2O3Na
(MþNa)þ calcd 271.1053, found 271.1055.
4.6.31. 1-Cyclopropyluracil (10d). The title compound was prepared
from 9d (0.45 g, 1.988 mmol) according to general method E in 97%
yield (0.35 g, 1.944 mmol) of white solid. nmax(KBr) 3145 (w, br),
2998 (m, br), 2954 (m), 2876 (m), 1714 (s, sh), 1700 (vs), 1678 (vs),
1615 (m), 1472 (m), 1453 (w, sh), 1430 (w), 1421 (m), 1384 (m), 1268
(s), 765 (w). dH (500.0 MHz, DMSO-d6) 1.52–1.65 (4H, m, H-20a, 30a,
40a and H-50a), 1.75 (2H, m, H-30b and H-40b), 1.91 (2H, m, H-20b and
H-50b), 4.70 (1H, m, H-10), 5.56 (1H, dd, J(5,6)¼8.0, J(5,3)¼2.3, H-5),
7.65 (1H, d, J(6,5)¼8.0, H-6), 11.22 (1H, br s, H-3). dC (125.7 MHz,
DMSO-d6) 23.84 (C-30 and C-40), 30.72 (C-20and C-50), 56.50 (C-10),
101.59 (C-5), 142.74 (C-6), 151.32 (C-2), 163.51 (C-4). HRMS
C9H13N2O2 (MþH)þ calcd 181.0972, found 181.0972.
4.6.27. 1-(3-Ethoxy-2-methylacryloyl)-3-naphthalen-2-ylurea
(9t). The title compound was prepared according to general
method A from compound 8m (0.186 g, 1.3 mmol) and reagent 7b
in 90% yield (0.35 g, 1.174 mmol) of white solid. nmax(KBr) 3268 (m),
3171 (w), 3150 (w), 3054 (w), 2986 (w), 2939 (w), 2898 (w), 1702
(vs), 1668 (s), 1655 (m, sh), 1617 (m), 1605 (m), 1588 (s), 1572 (s),
1512 (w), 1493 (w, sh), 1471 (m), 1396 (w), 1388 (w, sh), 1361 (w),
1286 (w), 1260 (w), 1216 (vs), 1180 (m), 1123 (s), 1042 (w), 1013 (w),
882 (w), 848 (w), 806 (w), 753 (w), 739 (w), 616 (vw), 469 (w). dH
(499.8 MHz, CDCl3) 1.26 (3H, t, J(CH3,CH2)¼7.1, CH2CH3), 1.87 (3H, d,
J(CH3,6)¼1.2, 5-CH3), 4.02 (2H, q, J(CH2,CH3)¼7.1, OCH2CH3), 7.40
(1H, m, H-60), 7.46 (1H, m, H-70), 7.52 (1H, dd, J(30,40)¼8.7,
J(30,10)¼2.2, H-30), 7.52 (1H, q, J(6,CH3)¼1.2, H-6), 7.77–7.81 (3H, m,
H-40, H-50 and H-80), 8.15 (1H, d, J(10,30)¼2.1, H-10), 8.37 (1H, br s, H-
3), 11.14 (1H, br s, H-1). dC (125.7 MHz, CDCl3) 8.90 (5-CH3), 15.28
(CH2CH3), 70.45 (OCH2CH3), 106.57 (C-5), 117.08 (C-10), 120.58 (C-
30), 124.92 (C-60), 126.43 (C-70), 127.54 and 127.58 (C-50 and C-80),
128.69 (C-40), 130.60 (C-40a), 133.86 (C-80a), 134.89 (C-20), 151.92 (C-
2), 158.03 (C-6), 169.80 (C-4). HRMS for C17H18N2O3Na (MþNa)þ
calcd 321.1210, found 321.1209.
4.6.32. 1-Cyclohexyluracil (10e). The title compound was prepared
from 9e (0.50 g, 2.08 mmol) according to general method E in 99%
yield (0.40 g, 2.061 mmol) of white solid. nmax(KBr) 2930 (s), 2865
(m), 1714 (vs, sh), 1690 (vs, br), 1676 (vs, br), 1616 (s), 1470 (s), 1452
(m), 1428 (m), 1419 (s), 1379 (s), 1268 (s), 763 (m). dH (500.0 MHz,
DMSO-d6) 1.13 (1H, qt, Jgem¼J(40ax,30ax)¼J(40ax,50ax)¼13.0,
J(40ax,30eq)¼J(40ax,50eq)¼3.6, H-40ax), 1.32 (2H, qt, Jgem
¼
J(30ax,20ax)¼J(30ax,40ax)¼13.2, J(30ax,20eq)¼J(30ax,40eq)¼3.4, H-30ax
and H-50ax), 1.54 (2H, qd, Jgem¼J(20ax,10)¼J(20ax,30ax)¼12.4,
J(20ax,30eq)¼3.7, H-20ax and H-60ax), 1.61 (1H, dm, Jgem¼12.9, H-
40eq), 1.69 (2H, m, H-20eq and H-60eq), 1.78 (2H, dm, Jgem¼13.5, H-
30eq and H-50eq), 4.23 (1H, tt, J(10,20ax)¼J(10,60ax)¼12.2,
J(10,20eq)¼J(10,60eq)¼3.8, H-10), 5.55 (1H, dd, J(5,6)¼8.0, J(5,3)¼2.3,
H-5), 7.70 (1H, d, J(6,5)¼8.0, H-6),11.22 (1H, br s, H-3). dC (125.7 MHz,
DMSO-d6) 24.85 (C-40), 25.56 (C-30 and C-50), 31.06 (C-20and C-60),
54.25 (C-10), 101.33 (C-5), 142.40 (C-6), 151.10 (C-2), 163.43 (C-4).
HRMS C10H14N2O2Na (MþNa)þ calcd 217.0947, found 217.0948.
4.6.28. (R)-1-(Pyrrolidin-3-yl)uracil (10a). The title compound was
prepared from 9a (1.72 g, 5.254 mmol) according to general
method E in 97% yield (0.92 g, 5.08 mmol) of white solid. NMR and
HRMS spectra were identical to those in Ref. 3.
4.6.33. 1-(trans-2-Hydroxycyclohexyl)uracil (10f). The title com-
pound was prepared from 9f (0.33 g, 1.28 mmol) according to
general method E in 78% yield (0.210 g, 0.998 mmol) of white solid.
nmax(KBr) 3348 (s), 3287 (m, br, sh), 3162 (m, br), 3021 (m, br), 2937
(s), 2862 (m), 1728 (s), 1694 (vs, br), 1662 (s, sh), 1625 (s), 1474 (s),
1427 (m), 1457 (m), 1388 (s), 1271 (s), 1074 (m), 764 (w). dH
(499.8 MHz, DMSO-d6) 1.21–1.29 (3H, m, H-30a, 40a and H-50a), 1.56
(1H, br s, H-60a), 1.62–1.71 (3H, m, H-40b, 50b and H-60b), 1.94 (1H,
m, H-30b), 3.64 (1H, br s, H-20), 4.06 (1H, br s, H-10), 4.89 (1H, br d,
J(OH,20)¼5.0, OH), 5.54 (1H, d, J(5,6)¼7.9, H-5), 7.67 (1H, d,
J(6,5)¼7.9, H-6), 11.12 (1H, br s, H-3). dC (125.7 MHz, DMSO-d6)
4.6.29. 1-((3R,4S)-4-Hydroxypyrrolidin-3-yl)uracil (10b). The title
compound was prepared from 9b (1.13 g, 1.75 mmol) according to
general method E and was re-purified using preparative reversed-
phase HPLC in 90% yield (0.31 g, 1.575 mmol) of white solid.
nmax(KBr) 3397 (m), 3312 (m), 2599 (w, vbr), 1698 (vs), 1677 (s),
1620 (w, sh), 1467 (w), 1388 (m), 1270 (m), 1084 (w), 1053 (w), 802
(m), 768 (w). dH (600.1 MHz, D2O) 3.00 (1H, dd, Jgem¼12.9,