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L. Petersen et al.
PAPER
1H NMR (300 MHz, DMSO-d6): = 3.98 (s, 2H, CH2Ph), 7.28
7.37 (m, 5H, Harom), 11.44 (br s, 1H, NH), 11.47 (br s, 1H, NH).
column chromatography (CH2Cl2) to give 6 as a white solid; yield
1.19 g (42%); mp 148 150 °C; Rf = 0.73 (5% EtOH/CH2Cl2).
13C NMR (75 MHz, DMSO-d6): = 41.64 (CH2Ph), 73.44 (C-5),
127.04, 128.42, 128.70, 135.45 (Carom), 151.00 (C-2), 155.57 (C-6),
161.94 (C-4).
1H NMR (300 MHz, CDCl3): = 1.19 (t, 3H, J = 7.1 Hz,
OCH2CH3), 2.43 (s, 3H, CH3Ar), 3.63 (q, 2H, J = 7.1 Hz, OCH2),
5.19 (s, 2H, CH2Ph), 5.29, (s, 2H, NCH2), 5.43 (dd, 1H, J = 1.7,
11.8 Hz, Hvinyl), 6.02 (dd, 1H, J = 1.7, 17.5 Hz, Hvinyl), 6.48 (dd, 1H,
J = 11.8, 17.5 Hz, Hvinyl), 7.19 7.87 (m, 9H, Harom).
13C NMR (75 MHz, CDCl3): = 14.89 (CH2CH3), 21.77 (CH3Ar),
33.85 (CH2Ph), 65.43 (OCH2), 73.11 (NCH2), 112.79 (C-5), 121.50
(Carom), 126.69 (Cvinyl), 127.50 (Carom), 127.58 (Cvinyl), 128.99,
129.48, 130.03, 130.64, 135.06, 146.55 (Carom), 150.42 (C-2),
150.60 (C-4), 161.26 (C-6), 168.43 (CO).
6-Benzyl-1-ethoxymethyl-5-iodo-1H-pyrimidine-2,4-dione (4)
BSA (0.71 g, 3.5 mmol) was dissolved in dry CHCl3 (20 mL) and
6-benzyl-5-iodo-1H-pyrimidine-2,4-dione (3, 0.33 g, 1 mmol) was
added. After 10 min, chloromethylethyl ether [0.15 g (95%),
1.5 mmol] and CsI (0.26 g, 1 mmol) were added. The solution was
stirred at r.t. under N2 for 3 h and then quenched with sat. NaHCO3
(20 mL). The aqueous phase was extracted with CH2Cl2 (2 20
mL). The organic phase was dried (MgSO4) and evaporated under
reduced pressure. The product was purified by silica gel column
chromatography (50% EtOAc/PE) to give 4 as white crystals; yield
0.32 g (82%); mp 174 176 °C; Rf = 0.62 (10% EtOH/CH2Cl2).
EIMS: m/z = 404 (M+).
Anal. Calcd for C24H24N2O4•0.5H2O (413.5): C, 69.72; H, 5.73; N,
6.78. Found: C, 69.82; H, 5.96; N, 6.71.
1H NMR (300 MHz, CDCl3): = 1.19 (t, 3H, J = 7.0 Hz, CH3), 3.62
(q, 2H, J = 7.1 Hz, OCH2), 4.56 (s, 2H, CH2Ph), 5.22 (s, 2H, NCH2),
7.17 7.39 (m, 5H, Harom), 9.59 (br s, 1H, NH).
13C NMR (75 MHz, CDCl3): = 14.97 (CH3), 41.99 (CH2Ph), 65.33
(OCH2), 73.98 (NCH2), 79.23 (C-5), 127.43, 127.59, 129.31,
133.51 (Carom), 151.55 (C-2), 155.99 (C-4), 160.14 (C-6).
6-Benzyl-1-ethoxymethyl-5-vinyl-1H-pyrimidine-2,4-dione (7)
6-Benzyl-1-ethoxymethyl-3-(4-methylbenzoyl)-5-vinyl-1H-pyrim-
idine-2,4-dione (6, 1.11 g, 2.74 mmol) was dissolved in a sat. solu-
tion of NH3 in MeOH (50 mL) and stirred at r.t. for 3 days. Then the
solution was acidified (pH = 3) with 4 M HCl. After cooling, the
precipitate was filtered from the solution, washed with H2O, and
dried in vacuo to give 7 as white crystals; yield 0.659 g (84%); mp
133 136 °C; Rf = 0.30 (5% EtOH/CH2Cl2).
EIMS: m/z = 386 (M+).
Anal. Calcd for C14H15IN2O3 (386.2): C, 43.54; H, 3.92; N, 7.25.
Found: C, 43.96; H, 3.97; N, 7.05.
1H NMR (300 MHz, CDCl3): = 1.19 (t, 3H, J = 7.1 Hz,
OCH2CH3), 3.63 (q, 2H, J = 7.1 Hz, OCH2), 4.29 (s, 2H, CH2Ph),
5.18 (s, 2H, NCH2), 5.43 (dd, 1H, J = 2.0, 11.7 Hz, Hvinyl), 5.99 (dd,
1H, J = 1.6, 17.4 Hz, Hvinyl), 6.47 (dd, 1H, J = 11.8, 17.4 Hz, Hvinyl),
7.13 7.38 (m, 5H, Harom), 9.64 (br s, 1H, NH).
6-Benzyl-1-ethoxymethyl-5-iodo-3-(4-methylbenzoyl)-1H-pyri-
midine-2,4-dione (5)
13C NMR (75 MHz, CDCl3): = 14.89 (CH2CH3), 33.77 (CH2Ph),
65.10 (OCH2), 72.82 (NCH2), 113.03 (C-5), 121.12, 127.05 (Cvinyl),
127.42, 127.46, 129.36, 135.30 (Carom), 150.73 (C-2), 151.52 (C-4),
162.45 (C-6).
6-Benzyl-1-ethoxymethyl-5-iodo-1H-pyrimidine-2,4-dione
(4,
5.02 g, 13 mmol) was dissolved in dry pyridine (150 mL) containing
N-ethyl-N,N-diisopropylamine (3.36 g, 26 mmol). The solution was
cooled to 0 °C and p-toluoyl chloride (4.02 g, 26 mmol) was added.
The solution was allowed to warm to r.t. and then stirred for 2.5 h.
Then H2O (20 mL) was added and the solvent was evaporated under
reduced pressure. The residue was dissolved in CHCl3 (100 mL).
The organic phase was washed with H2O (2 100 mL), dried
(MgSO4), and evaporated under reduced pressure. The residue was
purified by silica gel column chromatography (CH2Cl2) to give 5 as
white foam; yield 4.38 g (67%); mp 162 163 °C (EtOH/H2O);
Rf = 0.22 (CH2Cl2).
1H NMR (300 MHz, CDCl3): = 1.20 (t, 3H, J = 7.0 Hz,
OCH2CH3), 2.43 (s, 3H, CH3Ar), 3.62 (q, 2H, J = 7.0 Hz, OCH2),
4.62 (s, 2H, CH2Ph), 5.23 (s, 2H, NCH2), 7.23 7.83 (m, 9H, Harom).
13C NMR (75 MHz, CDCl3): = 14.86 (OCH2CH3), 21.79 (CH3Ar),
42.06 (CH2Ph), 65.60 (OCH2), 74.26 (NCH2), 78.96 (C-5), 127.57,
127.82, 128.41, 129.52, 130.07, 130.71, 133.48, 146.81 (Carom),
150.69 (C-2), 155.94 (C-4), 158.93 (C-6), 167.42 (COAr).
EIMS: m/z = 286 (M+).
Anal. Calcd for C16H18N2O3•0.25H2O (290.8): C, 66.08; H, 6.14; N,
9.49. Found: C, 66.09; H, 6.33; N, 9.50.
6-Benzyl-5-hydroxymethyl-1H-pyrimidine-2,4-dione (8)
6-Benzyl-1H-pyrimidine-2,4-dione (2, 2.02 g, 10 mmol) was dis-
solved in 1.25 M hot aq NaOH (22 mL). A 37% solution of formal-
dehyde in 10% MeOH/H2O (2.43 g, 30 mmol) was added and the
solution stirred at r.t. for 2 days. The solution was filtered and the
filtrate was washed with Et2O. The solid compound was dissolved
in hot H2O (50 mL) and the solution was acidified with 4 M HCl
(3 mL). After cooling, the mixture was filtered, the solid compound
was washed with H2O, and dried in vacuo to give 8 as a light-brown
solid; yield: 1.83 g (79%); mp 194 195 °C; Rf = 0.50 (20% EtOH/
CH2Cl2).
EIMS: m/z = 504 (M+).
1H NMR (300 MHz, DMSO-d6): = 3.85 (s, 2H, CH2Ph), 4.26 (s,
2H, CH2OH), 4.80 (s, 1H, OH), 7.23 7.36 (m, 5H, Harom), 10.85 (br
s, 1H, NH), 11.10 (br s, 1H, NH).
Anal. Calcd for C22H21IN2O4 (504.3): C, 52.40; H, 4.20, N, 5.55.
Found: C, 52.77; H, 3.98; N, 5.45.
13C NMR (75 MHz, DMSO-d6): = 35.09 (CH2Ph), 53.44
(CH2OH), 110.417 (C-5), 127.24, 128.95, 129.01, 136.98 (Carom),
151.51 (C-2), 152.94 (C-6), 164.99 (C-4).
6-Benzyl-1-ethoxymethyl-3-(4-methylbenzoyl)-5-vinyl-1H-py-
rimidine-2,4-dione (6)
6-Benzyl-1-ethoxymethyl-5-iodo-3-(4-methylbenzoyl)-1H-pyrimi-
dine-2,4-dione (5, 3.53 g, 7 mmol) and tetrakis(triphenylphos-
phine)palladium(0) (0.474 g, 0.4 mmol) were dissolved in HMPA
(70 mL) under Ar. Tetravinyltin (1.59 g, 7 mmol) was added while
stirring. The mixture was heated to 75 °C and stirred at this temper-
ature for two days. Then H2O (200 mL) was added, and the mixture
was extracted with Et2O (6 150 mL). The combined organic phas-
es were washed with H2O (4 50 mL), dried (MgSO4), and evapo-
rated under reduced pressure. The residue was purified by silica gel
EIMS: m/z = 232 (M+).
Anal. Calcd for C12H12N2O3 (232.2): C, 62.06; H, 5.21; N, 12.06.
Found: C, 61.91; H, 5.13; N, 11.95.
6-Benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbalde-
hyde (9) from 8
6-Benzyl-5-hydroxymethyl-1H-pyrimidine-2,4-dione (8, 0.232 g,
1 mmol) was dissolved in CH3CN/H2O (1:1, 15 mL). The solution
Synthesis 2001, No. 4, 559–564 ISSN 0039-7881 © Thieme Stuttgart · New York