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M. Ban et al./Bioorg. Med. Chem. 6 (1998) 1057±1067
Dibenzyl 6-piperidinopyrimidine 2,4-dioxamate hemi-
hydrate (2e). From 2,4-diamino-6-piperidinopyrimidine
(5.8 g) and benzyl oxalyl chloride (12.5 g): 9.2 g; mp 155±
159 ꢀC. 1H NMR (DMSO-d6) d: 10.96 (1H, s), 10.30
(1H, s), 7.46±7.15 (10H, m), 6.92 (1H, s), 5.28 (2H, s),
5.21 (2H, s), 3.60±3.35 (4H, m), 1.68±1.30 (6H, m).
2,4-Bis(2-furoylamino)-6-piperidinopyrimidine mono-
hydrate (2j). From 2,4-diamino-6-piperidinopyrimidine
(5.4 g) and 2-furoyl chloride (6.0 mL): 4.1 g; mp 148±
150 ꢀC. H NMR (CDCl3) d: 9.33 (1H, s), 8.47 (1H, s),
1
7.50±7.21 (5H, m), 6.51±6.40 (2H, m), 3.72±3.46 (4H,
m), 1.75±1.42 (6H, m). Anal. calcd for C19H19
.
Anal. calcd for C27H27N5O6 1/2H2O: C, 61.59; H, 5.36;
N, 13.30, found: C, 61.79; H, 5.22; N, 13.32.
.
N5O4 H2O: C, 57.14; H, 5.30; N, 17.54, found: C, 57.41;
H, 5.33; N, 17.58.
Dimethyl 6-pyrrolidinopyrimidine 2,4-dioxamate (5c).
From 2,4-diamino-6-pyrrolidinopyrimidine (5.4 g) and
methyl oxalyl chloride (5.8 mL): 7.2 g; mp 161±162 ꢀC.
1H NMR (DMSO-d6) d: 10.86 (1H, s), 10.10 (1H, s),
6.18 (1H, s), 3.82 (3H, s), 3.78 (3H, s), 3.52±3.10 (4H,
m), 2.10±1.70 (4H, m). Anal. calcd for C14H17
2,4-Bis(3,4-dimethoxycinnamoylamino)-6-piperidinopyr-
imidine (2k). The mixture of 3,4-dimethoxycinnamic
acid (10.1 g) and thionyl chloride (8.0 mL) was stirred at
55 ꢀC for 30 min. Thereafter thionyl chloride was dis-
tilled o under reduced pressure. The solution of 2,4-
diamino-6-piperidinopyrimidine (4.3 g) in pyridine
(200 mL) was added to the resulting crystals. The mixture
was stirred at room temperature overnight. Thereafter,
to the solution was added triethylamine (6.8 mL), and
pyridine was distilled o under reduced pressure. The
resulting crystals were ®ltered and washed water, and
recrystallized from dioxane/ethanol to give 2k; mp 237±
240 ꢀC. 1H NMR (DMSO-d6) d: 10.17 (1H, s), 9.77 (1H,
s), 7.67±6.85 (11H, m), 3.80 (12H, s), 3.57 (4H, s), 1.60
(6H, s). Calcd for C31H35O6: C, 64.91; H, 6.15; N, 12.21,
found: C, 64.90; H, 6.14; N, 12.15.
.
N5O7 H2O: C, 47.86; H, 4.88; N, 19.93, found: C, 47.82;
H, 4.76; N, 19.90.
Dimethyl 6-homopiperidinopyrimidine 2,4-dioxamate (6c).
From 2,4-diamino-6-homopiperidinopyrimidine (6.2 g)
and methyl oxalyl chloride (5.8mL): 7.3 g mp 130±135 ꢀC.
1H NMR (DMSO-d6) d: 10.84 (1H, s), 10.13 (1H, s), 6.82
(1H, s), 3.80 (3H, s), 3.75 (3H,s), 3.65±3.25 (4H, m), 1.85±
1.50 (8H, m). Anal. calcd for C16H21N5O6: C, 50.66; H,
5.58; N, 18.46, found: C, 50.78; H, 5.49; N, 18.41.
2,4-Bis(formylamino)-6-piperidinopyrimidine (2g). The
mixture of acetic anhydride (11.4 mL) and formic acid
(4.5 mL) was stirred at 60 ꢀC for 2 h. After cooling, 2,4-
diaminopyrimidine (5.8 g) was added to the solution at
room temperature. The mixture was stirred at room
temperature for 2 h. The resulting crystals were ®ltered
and washed with water. After drying, the solids were
recrystallized from ethyl acetate to give 3.9 g of 2g; mp
247 ꢀC (Dec.). 1H NMR (DMSO-d6) d: 10.30 (1H, s),
10.17 (1H, s), 9.35 (1H, s), 9.20 (1H, s), 5.82 (1H, s),
3.65±3.30 (4H, m), 1.78±1.25 (6H, m). Anal. calcd for
C11H15N5O2: C, 53.00; H, 6.07; N, 28.10, found: C,
52.97; H, 6.04; N, 28.36.
2,4-Bis(ethylsuccinylamino)-6-piperidinopyrimidine (2l).
From 2,4-diamino-6-methoxypyrimidine (5.8 g) and
ethyl succinyl chloride (9.0 mL): 8.9 g; mp 198±199 ꢀC.
1H NMR (DMSO-d6) d: 10.15 (1H, s), 9.64 (1H, s), 7.08
(1H, s), 4.04 (4H, q, J=7 Hz), 3.75±3.35 (4H, m), 3.10±
2.30 (8H, m), 1.80±1.30 (6H, m), 1.18 (6H, t, J=7 Hz).
Calcd for C21H31N5O6: C, 56.11; H, 6.95; N, 15.58,
found: C, 56.17; H, 7.00; N, 15.38.
2,4-Bis(methoxyacetylamino)-6-morpholinopyrimidine (3i).
From 2,4-diamino-6-morpholinopyrimidine (5.0 g) and
methoxyacetyl chloride (5.0 mL): 7.5 g; mp 189±191 ꢀC.
ꢀ
1H NMR (DMSO-d6) : 8.73 (1H, s), 8.48 (1H, s), 7.22
(1H, s), 4.05 (2H, S), 3.97 (2H, s), 3.68 (8H, m), 3.47
(3H, s), 3.45 (3H, s). Anal. calcd for C14H21N5O5: C,
49.55; H, 6.24; N, 20.64, found: C, 49.62; H, 6.20; N,
20.66.
2,4-Bis(acetylamino)-6-piperidinopyrimidine (2h). From
2,4-diamino-6-piperidinopyrimidine (5.8 g) and acetyl
chloride (4.5 mL): 5.7 g; mp 280 ꢀC (Dec.). 1H NMR
(DMSO-d6) d: 10.05 (1H, s), 9.50 (1H, s), 7.10 (1H, s),
3.60±3.20 (4H, m), 2.22 (3H, s), 2.08 (3H, s), 1.70±1.35
(6H, m). Anal. calcd for C13H19N5O2: C, 56.30; H, 6.91;
N, 25.25, found: C, 56.47; H, 6.89; N, 25.23.
2,4-Bis(methoxyacetylamino)-6-methoxypyrimidine (4i).
From 2,4-diamino-6-methoxypyrimidine (3.8 g) and
methoxyacetyl chloride (6.0 mL): 3.8 g; mp 168±169 ꢀC.
1H NMR (DMSO-d6) d: 10.02 (2H, s), 7.05 (1H, s), 4.26
(2H, s), 4.06 (2H, s), 3.87 (3H, s), 3.34 (6H, s). Anal.
calcd for C11H16N4O5: C, 46.48; H, 5.67; N, 19.71,
found: C, 46.69, H, 5.72; N, 19.98.
2,4-Bis(methoxyacetylamino)-6-piperidinopyrimidine (2i).
From 2,4-diamino-6-piperidinopyrimidine (5.0 g) and
methoxyacetyl chloride (5.0 mL) 2.7 g; mp 159±160 ꢀC.
2H NMR (DMSO-d6) d: 9.55 (1H, s), 9.48 (1H, s), 7.05
(1H, s), 4.20 (2H, s), 4.05 (2H, s), 3.53 (4H, s), 3.35 (3H,
s), 3.32 (3H, s), 1.60 (6H, s). Anal. calcd for C15H23N5O4:
C, 53.40; H, 6.87; N, 20.76, found: C, 53.46; H, 6.72; N,
20.81.
2,4-Bis(methoxyacetylamino)-6-chloropyrimidine (1i).
From 2,4-diamino-6-chloropirimidine (5.8 g) and
methoxyacetyl chloride (8.0): 3.2 g; mp 142±144 ꢀC
(Dec.). 1H NMR (DMSO-d6) d: 10.62 (1H, s), 10.42