oil. Purification by column chromatography on silica using
dichloromethane as eluent gave the enamine amide 17d (1.02 g,
50%, cis/trans ratio 1 : 1) as a clear oil; Rf 0.15 (CH2Cl2);
δH(CDCl3) 1.06, 1.15 (3 H, 2 × d, J 6.7, CH3), 1.44 (1 H, td,
J 2.2 and 13.1, CHCHaH(cis)), 1.89–2.01 (2 H, m, CHCH2-
(trans)), 2.59–2.69 (1 H, m, CHCHHb(cis)), 2.82–2.99 (1 H, m,
CHCH3), 3.93–4.03 (3 H, m, PhCH, CH2NHCC), 4.44–4.66
(2 H, m, CH2NHCO), 5.33–5.36 (1 H, m, CONH), 7.04–7.37
(15 H, m, Ar), 8.52–8.60 (1 H, m, NH); δC(CDCl3) 22.0,
23.0 (CH3), 34.8, 36.0 (CHCH3), 40.5, 42.8, 42.9, 43.0, 47.7,
1-Benzyl-2-thioxo-1,2,3,5,6,7-hexahydrocyclopentapyrimidin-4-
one (18d)
Ethyl 2-benzylaminocyclopent-1-enecarboxylate (17d) (1.0 g,
4.1 mmol) and trimethylsilyl isothiocyanate (3.0 ml, 21 mmol)
were refluxed for 3 h in an atmosphere of nitrogen. The cooled
reaction mixture was quenched with dropwise addition of sat-
urated aqueous NaHCO3 (10 ml) and water (10 ml). The mix-
ture was extracted with dichloromethane (3 × 50 ml). The com-
bined organic phases were dried and evaporated under reduced
pressure. Purification by column chromatography on silica
using dichloromethane and methanol (5%) as eluent gave the
thiouracil 18d (878 mg, 83%) as a light brown solid; mp 222–
228 ЊC; (Found: C, 65.3; H, 5.6; N, 10.6. C14H14N2OS, requires
C, 65.1; H, 5.5; N, 10.8%); Rf 0.45 (5% EtOH–CH2Cl2);
δH(CDCl3) 1.92 (2 H, quintet, J 7.5, CH2CH2CH2), 2.57, 2.78
(4 H, 2 × t, J 7.5, CH2CH2CH2), 5.58 (2 H, s, PhCH2), 7.21–7.39
(5 H, m, Ar), 12.59 (1 H, br s, NH); δC(CDCl3) 20.5 (CH2-
CH2CH2), 27.2, 32.6 (CH2CH2CH2), 52.8 (CH2N), 117.9
(C4a), 126.0, 127.2, 128.6, 135.6 (Ar), 157.6, 158.3 (C4 and
C7a), 177.2 (C2); m/z (EI) 258 (Mϩ, 100%), 91 (82).
47.6, 49.0 (CHCH , 2 × NCH , PhCH), 102.2, 102.3 (᎐CCO),
᎐
2
2
126.5, 126.6, 126.9, 127.2, 127.3, 127.5, 127.6, 128.4, 128.5,
128.6, 128.7, 128.8, 139.3, 139.4, 139.5, 139.6, 143.6, 144.1
(Ar), 161.0, 161.9 (NC᎐), 168.6, 168.7 (CON); m/z (MALDI-
᎐
peak matching) 419.20840 (MNaϩ). C27H28N2ONa requires
419.20938.
N-Benzyl-5-methyl-2-oxo-3-phenylcyclopentanecarboxamide
(17f)
Ethyl 5-methyl-2-oxo-3-phenylcyclopentanecarboxylate (16a)
(2.13 g, 8.65 mmol), benzylamine (0.75 ml, 6.90 mmol) and
PTSA (82 mg, 0.43 mmol) were refluxed for 1.5 h in dry toluene
(55 ml) in a Dean–Stark setup under an atmosphere of nitro-
gen. Evaporation under reduced pressure yielded a pink solid.
Purification by recrystallisation in toluene and petroleum ether
(1 : 1) gave 17e (1.13 g, 53% according to 16a) as white crystals;
mp 128.5–132.5 ЊC (toluene–petroleum ether); (Found: C, 78.1;
H, 6.9; N, 4.6. C20H21NO2, requires C, 78.2; H, 6.9; N, 4.6%); Rf
0.10 (CH2Cl2); δH(CDCl3) 1.33 (3 H, d, J 6.2, CH3), 1.69 (1 H,
dd, J 12.8 and 14.2, CHCHaH), 2.51–2.60 (1 H, m, CHHb), 2.66
(1 H, d, J 11.0, CHCO2), 2.71–2.80 (1 H, m, CHCH3) 3.50 (1 H,
dd, J 8.2 and 12.8, PhCH), 4.45 (2 H, d, J 5.9, CH2N), 6.95
(1 H, br s, NH), 7.13–7.35 (10 H, m, Ar); δC(CDCl3) 20.2 (CH3),
32.1 (CHCH3), 37.2 (CH2CH), 43.6 (CH2N), 56.5 (PhCH),
61.9 (CHCO2), 127.2, 127.3, 127.5, 128.1, 128.5, 128.6, 137.1,
137.9 (Ar), 166.5 (CO2), 213.5 (CO); m/z (EI) 307 (Mϩ, 63%), 91
(100).
1-Benzyl-5-methyl-7-phenyl-1,5,6,7-tetrahydrocyclopenta-
pyrimidine-2,4-dione (19)
1-Benzyl-5-methyl-7-phenyl-2-thioxo-1,2,3,5,6,7-hexahydro-
cyclopentapyrimidin-4-one (18a) (648 mg, 1.86 mmol, with a
cis/trans ratio of 2 : 3) was refluxed for 36 h in 25% aqueous
chloroacetic acid. A precipitate was formed on cooling the reac-
tion mixture. Purification by column chromatography on silica
using dichloromethane and methanol (3%) as eluent gave the
uracil 19 (195 mg, 32%, with a cis/trans ratio of 2 : 3) as a white
solid; mp 146–148 ЊC; (Found: C, 75.6; H, 6.2; N, 8.3.
C21H20N2O2, requires C, 75.9; H, 6.1; N, 8.4%); Rf 0.40 (5%
EtOH–CH2Cl2); δH(CDCl3) 1.28 (3 H, d, J 6.9, CHCH3(cis)),
1.32 (3 H, d, J 6.9, CHCH3(trans)), 1.54 (1 H, td, J 3.6 and 13.7,
CHCHaH(cis)), 1.94–2.05, 2.10–2.18 (2 H, 2 × m, CHCH2-
(trans)), 2.78 (1 H, td, J 9.9 and 13.7, CHCHHb(cis)), 3.15–3.22 (1
H, m, CHCH3(cis)), 3.32 (1 H, sextet, J 6.9, CHCH3(trans)),
3.96–4.01 (1 H, m, PhCH), 4.07, 5.26 (2 H, 2 × d, J 16.1, CH2N),
7.02–7.12, 7.23–7.40 (10 H, m, Ar), 8.51 (1 H, br s, NH);
δC(CDCl3) 19.7, 21.0 (CH3), 34.7, 34.9 (CHCH3), 41.4, 42.8
(CHCH2), 46.8, 47.0 (PhCH), 49.2, 49.6 (CH2N), 118.3 (C4a),
126.3, 126.4, 126.7, 127.0, 127.6, 127.7, 127.8, 127.8, 128.9, 128.9,
129.5, 129.5, 136.1, 140.6, 142.1 (Ar), 152.6, 157.5, 160.8 (C2, C4
and C7a); m/z (EI) 332 (Mϩ, 9%), 91 (100).
1-Benzyl-5-methyl-7-phenyl-2-thioxo-1,2,3,5,6,7-hexahydro-
cyclopentapyrimidin-4-one (18a)
Ethyl 2-benzylamino-5-methyl-3-phenylcyclopent-1-enecarb-
oxylate (17a) (680 mg, 2.03 mmol) and trimethylsilyl iso-
thiocyanate (4.3 ml, 30 mmol) were refluxed for 3.5 h in an
atmosphere of nitrogen. The cooled reaction mixture was
quenched with dropwise addition of saturated aqueous
NaHCO3 (15 ml) and water (10 ml). The mixture was extracted
with dichloromethane (3 × 25 ml). The combined organic
phases were dried and evaporated under reduced pressure.
Purification by column chromatography on silica using di-
chloromethane and methanol (2.5%) as eluent gave the thio-
uracil 18a (648 mg, 92%) as a light brown solid. On recrystallis-
ation from EtOH the cis/trans ratio of 18a changed from ∼2 : 3
to ∼1 : 4 and the mixture was isolated as a slightly yellow solid;
mp 212–213 ЊC (EtOH); (Found: C, 72.2; H, 5.8; N, 8.1.
C21H20N2OS, requires C, 72.4; H, 5.8; N, 8.0%); Rf 0.50 (5%
EtOH–CH2Cl2); δH(CDCl3), 1.29 (3 H, d, J 7.1, CHCH3(cis)),
1.34 (3 H, d, J 7.1, CHCH3(trans)), 1.56 (1 H, td, J 3.3 and
13.7, CHCHaH(cis)), 1.92–2.03, 2.09–2.17 (2 H, 2 × m,
CHCH2(trans)), 2.76 (1 H, td, J 9.9 and 13.7, CHCHHb(cis)),
3.20–3.25 (1 H, m, CHCH3(cis)), 3.36 (1 H, sextet, J 7.1,
CHCH3(trans)), 3.96–4.02 (1 H, m, PhCH), 4.30, 6.22 (2 H, 2 ×
d, J 16.2, CH2N(cis)), 4.38, 6.19 (2 H, 2 × d, J 16.2, CH2N-
(trans)), 7.03–7.15, 7.26–7.42 (10 H, m, Ar), 10.05 (1 H, br s,
NH); δC(CDCl3) 19.3, 20.6 (CH3), 35.0, 35.2 (CHCH3), 41.0
42.5 (CHCH2), 49.8, 50.2 (PhCH), 52.4, 52.6 (CH2N), 124.0,
125.1 (C4a), 125.8, 125.9, 126.6, 126.8, 127.7, 127.8, 127.9,
128.9, 129.0, 129.6, 129.7, 134.9, 134.9, 140.1, 141.8 (Ar), 158.0,
158.2 (C4 and C7a), 178.2 (C2); m/z (EI) 348 (Mϩ, 100%), 91
(20).
5-Methyl-7-phenyl-1,5,6,7-tetrahydrocyclopentapyrimidine-2,4-
dione (20)
1-Benzyl-5-methyl-7-phenyl-1,5,6,7-tetrahydrocyclo-
pentapyrimidine-2,4-dione (19) (127 mg, 0.38 mmol, with a cis/
trans ratio of 2 : 3) was heated at 165 ЊC for 30 min in PPA. The
dark green solution was cooled and water added. As the PPA
dissolved in the water, a brown solid crystallised. The solid was
filtered off and washed with water. Purification by column
chromatography on silica using dichloromethane and ethanol
(2.5%) as eluent gave the uracil 20 (36 mg, 39%, with a cis/trans
ratio of 1 : 1) as a slightly brown-coloured solid; (Found: C,
68.8; H, 5.7; N, 11.4. C14H14N2O2, 0.1 H2O requires C, 68.9; H,
5.8; N, 11.5%); mp 233–236 ЊC; Rf 0.20 (5% EtOH–CH2Cl2);
δH(DMSO-d6) 1.18, 1.20 (3 H, 2 × d, J 6.4, CHCH3), 1.36 (1 H,
td, J 5.3 and 13.3, CHaH(cis)), 2.01–2.08 (2 H, m, CH2(trans)),
2.80 (1 H, td, J 9.2 and 13.3, CHHb(cis)), 2.98, 3.12 (1 H, 2 ×
sextet, J 6.4, CHCH3), 4.11–4.19 (1 H, m, PhCH), 7.08–7.37
(5 H, m, Ar), 10.82, 10.90 (2 H, 2 × br s, NH); δC(DMSO-d6)
19.7, 20.6 (CH3), 34.0, 34.2 (CHCH3), 41.8 (CHCH2), 47.8,
48.3 (PhCH), 114.4, 115.0 (C4a), 126.6, 126.8, 127.3, 127.6,
128.5, 128.6, 141.8, 142.4 (Ar), 152.4, 152.5, 155.4, 156.2, 162.0,
162.1 (C2, C4 and C7a); m/z (MALDI-peak matching)
265.0948 (MNaϩ). C14H14N2O2Na requires 265.0948.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 9 0 8 – 2 9 1 8
2915