1
632
S. Tumkevicius, M. Dailide, A. Kaminskas
Vol 43
cooling to room temperature the reaction mixture was poured into
water (ca. 200 ml), the precipitate was collected by filtration, well
washed with water, methanol (5 ml), dried and recrystallised from
2,4-Diamino-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic
acid (8b).
A mixture of compound 6b (1.0 g, 4.5 mmol), methanol (20
ml), water (10 ml) and sodium hydroxide (0,44 g, 11 mmol) was
refluxed while stirring for 1 hour. Then the reaction mixture was
concentrated under reduced pressure to 1/3 of the initial volume
and acidified with dilute hydrochloric acid to pH 2. The
precipitate was collected by filtration, washed with water and
recrystallised from dimethylsulfoxide to give 0.88 g (94%) of
1
3
,4-dioxane to give 1.29 g (68 %) of 6a, mp 249-252°; ir (nujol):
-1 1
395, 3333, 3226, 3150 (NH ), 1691 (CO) cm ; H nmr
2
(
dimethylsulfoxide-d ): ꢀ 1.30 (t, J = 7.2 Hz, 3H, CH ), 4.28 (q, J
6
3
=
7.2 Hz, 2H, CH ), 6.51 (br. s, 2H, NH ), 7.35 (br. s, 2H, NH ),
2 2 2
13
8
1
.21 (s, 1H, C5-H). C nmr (dimethylsulfoxide-d ): ꢀ 15.0, 61.4,
09.8, 119.6, 128.0, 160.7, 162.9, 163.2, 172.7.
6
Anal. Calcd. for C H N O S: C, 45.37; H, 4.23; N, 23.51.
-1
-1
-1
9
10
4
2
8
3
b, mp >300° (dec.); ir (nujol): 3421 cm , 3318 cm , 3202 cm ,
-1 -1 1
Found: C, 45.58; H, 4.03; N, 23.62.
Method B.
130 cm (NH , OH); 1683 cm (CO); H-nmr (deuterated
2
trifluoroacetic acid): ꢀ 3,73 (3H, s, NCH ); 7,62 (1H, s, C5-H).
3
Anal. Calcd. for C H N O : C, 46.38; H, 4.38. Found: C,
8
9
5
2
To a solution of compound 5 (0.20 g, 1.16 mmol) in dry
dimethylformamide (5 ml) in sequence as following molecular
sieves 4 Å (0.2 g), ethyl mercaptoacetate (0.15 g, 1.3 mmol) and
anhydrous potassium carbonate (0.80 g, 5.8 mmol) were added.
The reaction mixture was stirred at 60° for 2 hours, cooled to
room temperature and poured into water (ca. 50 ml). The
precipitate was collected by filtration, washed with water (3 x 3
ml), methanol (1 ml), dried and recrystallised from 1,4-dioxane
to give 0.20 g (72 %) of 6a, whose properties were identical to
those of the product obtained in Method A.
4
6.63; H, 4.41.
N-(4-Methoxyphenyl)amide of 2,4-Diaminothieno[2,3-d]pyrim-
idine-6-carboxylic acid (9).
To a stirred suspension of compound 8a [18] (0.68 g, 3.2
mmol) in dry dimethylformamide (30 ml) N,N'-dicyclohexyl-
carbodiimide (1.0 g, 4.8 mmol), 1H-1,2,3-benzotriazol-1-ol
(0.65 g, 4.8 mmol) and 4-methoxyaniline (0.6 g, 4.8 mmol) were
added. The flask was capped with rubber septum, flushed with
argon gas and stirred at room temperature for 60 hours. Water
(
1
0.5 ml) was added and the mixture was stirred for an additional
hour. The precipitate was filtered off, washed with dimethyl-
Methyl 2,4-Diamino-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-
6
-carboxylate (6b).
formamide (1 ml) and the filtrate was poured into water (ca. 300
ml). The precipitate was collected by filtration, recrystallised
from a mixture of dimethylformamide and water, and dried in a
drying oven at ca. 105 °C to give 0.76 g (75 %) of 9, mp > 300°
To a mixture of compound 5 (1.0 g, 5.8 mmol), hydrochloride
of methyl N-methylglycinate (0.98 g, 7.0 mmol) and methanol
15 ml) triethylamine (1.30 g, 12.8 mmol) was added dropwise.
(
The reaction mixture was refluxed for 18 hours. Then an
additional amount of triethylamine (1.17 g, 11.6 mmol) was
added and the reaction mixture was refluxed for additional 18
hours. After cooling to room temperature the precipitate was
collected by filtration. Filtrate was concentrated to 1/3 of the
initial volume and poured into water. The precipitate was
collected by filtration, combined with that earlier obtained,
washed with water and recrystallised from methanol to give 0.76
g (59%) of 6b, mp > 260° (dec.); ir (nujol): 3421, 3324, 3117
(
dec.); ir (nujol): 3461, 3313, 3186 (2NH , NH), 1624 (CO)
2
-1
1
cm ; H nmr (dimethylsulfoxide-d ): ꢀ 3.77 (s, 3H, C4'-OCH ),
6
6
3
.38 (br. s, 2H, NH ), 6.94 (d, J = 9.2 Hz, 2H, C3',5'-H), 7.18
2
(br. s, 2H, NH ), 7.64 (d, J = 9.2 Hz, C2',C6'-H), 8.05 (s, 1H,
2
1
3
C5-H), 10.11 (br. s, 1H, CONH); C nmr (dimethylsulfoxide-
d ): ꢀ 55.9, 109.7, 114.5, 122.4, 124.0, 126.6, 132.8, 156.2,
160.6, 161.2, 162.7, 171.5; ms (m/z, % I): 315 (M , 7), 200 (48),
1
6
+
56 (16), 154 (36), 150 (100), 134 (15), 123 (18), 122 (31), 119
(58), 105 (26), 92 (36), 91 (68).
-1
1
(
NH ), 1712 (CO) cm ; H nmr (dimethylsulfoxide-d ): ꢀ 3.75
Anal. Calcd. for C H N O S: C, 53.32; H, 4.15; N, 22.21.
2
6
14 13
5
2
(
2
3
s, 3H, NCH ), 3.78 (s, 3H, OCH ), 6.05 (s, 2H, NH ), 6.99 (s,
Found: C, 53.10; H, 4.35; N, 22.42.
3
3
2
1
3
H, NH ), 7.32 (s, 1H, C5-H); C nmr (dimethylsulfoxide-d ): ꢀ
2
6
N-(3,4,5-Trimethoxyphenyl)amide of 2,4-Diaminothieno[2,3-d]-
pyrimidine-6-carboxylic acid (10).
1.4, 51.8, 96.8, 110.5, 120.5, 155.7, 156.0, 162.1, 162.9.
Anal. Calcd. for C H N O : C, 48.87; H, 5.01; N, 31.66.
9
11
5
2
Found: C, 49.01; H, 4.99; N, 31.96.
This compound was prepared analogously to
9 from
compound 8a (0.30 g, 1.4 mmol). The reaction time 24 hours.
Yield 0.26 g (49%), mp > 300° (dec.) (from a mixture of
dimethylformamide and water); ir (nujol): 3454, 3324, 3181
Ethyl N-(2,4-Diamino-5-formylpyrimidin-6-yl)glycinate (7).
To a mixture of compound 5 (1.0 g, 5.8 mmol), hydrochloride
of ethyl glycinate (0.98 g, 7 mmol) in ethanol (15 ml) triethyl-
amine (1.3 g; 12.8 mmol) was added dropwise. The reaction
mixture was refluxed while stirring for 40 hours. After cooling
to room temperature the precipitate was collected by filtration,
washed with water and recrystallised from methanol to give 0.60
g (43%) of 7, mp > 200° (dec.); ir (nujol): 3418, 3319, 3143
-1
1
(NH , NH), 1628 (CO) cm ; H nmr (dimethylsulfoxide-d ): ꢀ
2
6
3.66 (s, 3H, C4'-OCH ), 3.78 (s, 6H, C3',5'-OCH ), 6.40 (br. s,
3
3
2H, NH ), 7.17 (s, 2H, C2',6'-H) 7.20 (br. s, 2H, NH ,), 8.06 (s,
2
2
1
3
1H, C5-H), 10.14 (br. s, 1H, CONH); C nmr (dimethyl-
sulfoxide-d ): ꢀ 56.4, 60.8, 98.4, 109.7, 124.2, 126.5, 134.2,
6
135.9, 153.3, 160.6, 161.4, 162.7, 171.6.
-1
1
(
NH , NH), 1731, 1691 (CO) cm ; H nmr (dimethylsulfoxide-
Anal. Calcd. for C H N O S: C, 51.19; H, 4.56; N, 18.66.
2
16 17
5
4
d ): ꢀ 1.22 (t, J = 7.0 Hz, 3H, CH ), 4.13 (q, J = 7.0 Hz, 2H,
Found: C, 51.22; H, 4.68; N, 18.91.
6
3
OCH2), 4.18 (d, J = 6.3 Hz, 2H, NCH ), 6.56 (br. s, 2H, NH ),
2
2
N-(4-{[(2,4-diaminothieno[2,3-d]pyrimidin-6-yl)carbonyl]amino}-
benzoyl)-L-glutamic acid (11).
6
.97 (br. s, 2H, NH ), 9.44 (br. s, 1H, NH), 9.80 (s, 1H, CHO);
C nmr (dimethylsulfoxide-d ): ꢀ 19.6, 47.1, 65.9, 96.0, 168.7,
2
1
3
6
1
69.2, 171.7, 175.7, 189.0.
To a stirred suspension of compound 8a (0.285 g, 1.36 mmol)
in dry dimethylformamide (12 ml) N,N'-dicyclohexylcarbo-
diimide (0.56 g, 2.7 mmol), 1H-1,2,3-benzotriazol-1-ol (0.27 g,
Anal. Calcd. for C H N O : C, 45.19; H, 5.48; N, 29.27.
9
13
5
3
Found: C, 45.50; H, 5.21; N, 29.43.