1176
A. Z. M. S. Chowdhury, Y. Shibata, M. Morita, K. Kaya and K. Hiratani
Vol. 38
chloro product 5, 2.92 g (68%), mp 140-142°. This compound,
obtained solid was recrystallized from ethanol to give 7 as pale
without further purification and analysis, was used in the next step.
red crystals, 0.27 g (61%).
3
-(2-Ethoxycarbonylmethyl)-2-pentylamino-4(3H)-pteridinone
Method B.
(
6a).
A solution of the methylthio derivative 4 (0.56 g, 2 mmol) and
99% of hydrazine hydrate (5 ml) in absolute ethanol (8 ml) was
stirred and heated under reflux for 8 hours. The solvent was evapo-
rated under reduced pressure. The solid was washed with water and
recrystallized from isopropanol to give pale red crystals, 0.22 g
A solution of the chloro product 5 (0.54 g, 2 mmol) and pentyl-
amine (0.26 g, 3 mmol) in triethylamine (5 ml) was refluxed for 8
hours. The solvent was evaporated in vacuo. The obtained solid
was recrystallized from ethyl acetate to give 6a as white crystals,
0
1
1
1
1
.34 g (53%), mp 213-215°; H nmr (deuteriochloroform): δ
.10 (t, J = 7.0 Hz, 3H, Me), 1.20 (t, J = 7.1 Hz, 3H, Me), 1.30-
.70 (m, 6H, -CH -CH -CH -), 3.30 (m, 2H, N-CH ), 4.25-4.28
(51%), mp 294-296 °; H nmr (deuteriochloroform): δH 4.45 (s,
H
2H, 3-H), 5.30 (s, 2H, NH ) 8.68 (d, J = 2.4 Hz, 1H, 7-H), 8.87 (d,
2
13
J = 2.4 Hz, 1H, 8-H); C nmr (dimethyl-d sulfoxide): δ 46.40 (t,
2
2
2
2
6
C
(
8
q, J = 7.1 Hz, 2H, OCH ), 4.84 (s, 2H, CH ), 6.00 (s, 1H, NH),
C-3), 128.90 (s, C-5a), 142.75 (d, C-7), 147.98 (s, C-9a), 150.84 (d,
C-8), 154.75 (s, C-10a), 162.90 (s, C=O), 166.35 (s, C=O).
Anal. Calcd. for C H N O : C, 44.04; H, 2.77; N, 38.51.
2
2
1
3
.59 (d, J = 2.4 Hz, 1H, 6-H), 8.74 (d, J = 2.4 Hz, 1H, 7-H);
C
nmr (deuteriochloroform): δC 13.63 (q, Me), 13.79 (q, Me),
2
4
8
6 6 2
2.12 (t, CH ), 28.80 (t, CH ), 28.91 (t, CH ), 39.56 (t, N-CH ),
Found: C, 44.13; H, 2.89; N, 38.37.
2
2
2
2
6.94 (t, CH ), 61.80 (t, OCH ), 128.70 (s, C-4a), 142.80 (d,
2
2
2,3-Dihydro-5H-thiazolo[2,3-b]pteridin-5-one (8).
C-6), 147.65 (s, C-8a), 149.95 (d, C-7), 160.40 (s, C-2), 162.44
(
s, C=O), 165.95 (s, C=O).
A solution of methyl 2-aminopyrazine-3-carboxylate (1, 0.61
Anal. Calcd. for C H N O : C, 56.41; H, 6.62; N, 21.92.
g, 4 mmol) and 2-(methylthio)-2-thiazoline (0.66 g, 5 mmol) in
dry acetic acid (6 ml) was heated to 100° for 10 hours. After cool-
ing to room temperature, crushed ice (100 g) was added and the
mixture stirred for 1 hour. The separated product was collected
and recrystallized from methanol to give 8 as yellow crystals,
1
5 21 5 3
Found: C, 56.60; H, 6.80; N, 21.75.
3
-(2-Ethoxycarbonylmethyl)-2-(1-pyrrolidinyl)-4(3H)-pteridi-
none (6b).
A solution of the chloro product 5 (0.54 g, 1 mmol) and pyrroli-
dine (0.98 g, 3 mmol) in triethylamine (5 ml) was refluxed for 6
hours. The solvent was evaporated in vacuo. The obtained solid
0
.43 g, (53%), mp 292-293° (decomposed) (Lit. [14,15] >300°);
1
H nmr (deuteriochloroform): δH 3.50 (t, J = 7.8 Hz, 2H, 2-H),
4
.50 (t, J = 7.8 Hz, 2H, 3-H), 8.77 (d, J = 1.9 Hz, 1H, 7-H), 8.88
was recrystallized from ethanol to give 6b as white crystals, 0.35 g
13
(d, J = 1.9 Hz, 1H, 8-H); C nmr (deuteriochloroform): δ 26.72
C
1
(
57%), mp 225-227°; H nmr (deuteriochloroform): δ 1.22 (t, J =
H
(t, C-2), 48.10 (t, C-3), 132.55 (s, C-5a), 138.08 (d, C-7), 147.16
(s, C-9a), 147.90 (d, C-8), 150.01 (s, C-10a), 162.45 (s, C=O).
7
.1 Hz, 3H, Me), 1.75-1.95 (m, 4H, -CH -CH -), 3.34-3.51 (m,
2 2
4
H, -H C-N-CH -), 4.30 (q, J = 7.1 Hz, 2H, CH O), 4.76 (s, 2H,
2
2
2
Anal. Calcd. for C H N OS: C, 46.59; H, 2.93; N, 27.16.
8 6 4
CH ), 8.65 (d, J = 2.4 Hz, 1H, 6-H), 8.79 (d, J = 2.4 Hz, 1H, 7-H);
2
Found: C, 46.68; H, 3.06; N, 27.31.
13
C nmr (dimethyl-d sulfoxide): δ 14.20 (q, Me), 25.40 (t, -CH -
6
C
2
3
,4-Dihydro-2H,6H-[1,3]thiazino[2,3-b]pteridin-6-one (9).
CH -), 47.20 (t, CH ), 50.50 (t, -H C-N-CH -), 61.88 (t, OCH ),
2
2
2
2
2
1
1
28.65 (s, C-4a), 142.48 (d, C-6), 147.52 (s, C-8a), 150.20 (d, C-7),
60.25 (s, C-2), 162.14 (s, C=O), 165.89 (s, C=O).
The title compound was prepared in the same manner as 8
from methyl 2-aminopyrazine-3-carboxylate (1, 0.61 g, 4 mmol)
and 5,6-dihydro-2-(methylthio)-4H-1,3-thiazine (0.73 g, 5
mmol), reaction time 5 hours and recrystallized from ethanol to
Anal. Calcd. for C H N O : C, 55.44; H, 5.64; N, 23.08.
1
4 17 5 3
Found: C, 55.60; H, 5.49; N, 23.26.
-(2-Ethoxycarbonylmethyl)-2-(4-morpholinyl)-4(3H)-pteridi-
none (6c).
The title compound was prepared in the same manner as 6a
from chloro product 5 (0.54 g, 2 mmol) and morpholine (0.26 g,
afford 9 as colourless crystals, 0.37 g (42%), mp 283-285° (Lit.
3
1
[
3
8
14] 285-287°); H nmr (deuteriochloroform): δ 2.30 (m, 2H,
H
-H), 3.20 (t, J = 7.5 Hz, 2H, 2-H), 4.20 (t, J = 6.5 Hz, 2H, 4-H),
13
.77 (d, J = 2.1 Hz, 1H, 8-H), 8.81 (d, J = 2.1 Hz, 1H, 9-H);
C
nmr (deuteriochloroform): δC 22.95 (t, C-3), 27.86 (s, C-2),
0.95 (t, C-4), 132.20 (s, C-6a), 138.41 (d, C-8), 147.32 (C-9),
47.85 (s, C-10a), 153.52 (s, C-11a), 161.85 (s, C=O).
3
mmol), reaction time 8 hours and recrystallized from ethanol to
4
1
1
give 6c as white crystals, 0.36 g (56%), mp 163-165°; H nmr
(deuteriochloroform): δH 1.25 (t, J = 7.1 Hz, 3H, Me), 3.15 (m,
Anal. Calcd. for C H N OS: C, 49.07; H, 3.65; N, 25.43.
9
8 4
4
H, -H C-N-CH -), 3.80 (m, 4H, -H C-O-CH -), 4.30 (q, 2H,
2
2
2
2
Found: C, 49.27; H, 3.77; N, 25.14.
CH O), 4.65 (s, 2H, CH ), 8.58 (d, J = 2.4 Hz, 1H, 6-H), 8.76 (d,
J = 2.4 Hz, 1H, 7-H); C nmr (deuteriochloroform): δ 14.04 (q,
2
2
1
3
2,3-Dihydroimidazo[2,1-b]pteridin-5(1H)-one (10).
C
Me), 26.65 (t, C-8), 50.47 (t, -H C-N-CH -), 61.60 (t, OCH ),
2
2
2
A solution of methyl 2-aminopyrazine-3-carboxylate 1, (0.61 g, 4
mmol) and 2-(methylthio)-2-imidazoline (0.69 g, 6 mmol) in hexa-
methylphosphoric triamide (HMPTA, 5 ml) was heated to 150° for
6
1
6.20 (t, -H C-O-CH -), 128.15 (s, C-4a), 142.35 (d, C-6),
47.48 (s, C-8a), 150.13 (d, C-7), 160.01 (s, C-2), 162.09 (s,
2 2
C=O), 165.46 (s, C=O).
3
hours. After cooling to room temperature, crushed ice (70 g) was
Anal. Calcd for C H N O : C, 52.66; H, 5.36; N, 21.93.
1
4
17
5
4
added and the mixture stirred for 1 hour. The separated product was
Found: C, 52.53; H, 5.27; N, 21.76.
collected and crystallized from ethyl acetate to give 10 as pale red
1
crystals, 0.40 g (53%), mp 295-297° (decomposed); H nmr (deu-
1-Aminoimidazo[2,1-b]pteridin-2,5(1H,3H)-dione (7).
teriochloroform): δH 3.70 (t, J = 6.7 Hz, 2H, 2-H), 4.09 (t, J = 6.7
Hz, 2H, 3-H), 8.62 (d, J = 1.9 Hz, 1H, 7-H), 8.86 (d, J = 1.9 Hz, 1H,
Method A.
13
A solution of the chloro product 5 (0.54 g, 2 mmol) and 99% of
hydrazine hydrate (0.10 g, 3 mmol) in triethylamine (5 ml) was
refluxed for 5 hours. The solvent was evaporated in vacuo. The
8-H), 9.65 (s, 1H, NH); C nmr (deuteriochloroform): δ 40.69 (t,
C
C-2), 45.13 (t, C-3), 128.80 (s, C-5a), 141.84 (d, C-7), 146.80 (s,
C-9a), 148.94 (C-8), 153.72 (d, C-10a), 165.07 (s, C=O).