Synthesis of pyrrolo[2,3-d]pyrimidines with 3-amino-2-hydroxypropyl substituents

Article abstract of DOI:10.1007/s10593-012-1019-x

A novel route has been found for the synthesis of pyrimido[5',4':4,5] pyrrolo[2,1-c][1,4]oxazines. They are promising reagents for the preparation of pyrrolo[2,3-d]pyrimidine-6-carboxylic acid amides which contain a 3-amino-2-hydroxypropyl substituent in

Full text of DOI:10.1007/s10593-012-1019-x

Chemistry of Heterocyclic Compounds, Vol. 48, No. 3, June, 2012 (Russian Original Vol. 48, No. 3, March, 2012)
SYNTHESIS OF PYRROLO[2,3-d]PYRIMIDINES WITH
3-AMINO-2-HYDROXYPROPYL SUBSTITUENTS
L. V. Muzychka1, E. V. Verves1, I. O. Yaremchuk1, and O. B. Smolii1*
A novel route has been found for the synthesis of pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazines. They
are promising reagents for the preparation of pyrrolo[2,3-d]pyrimidine-6-carboxylic acid amides which
contain a 3-amino-2-hydroxypropyl substituent in position 7 of the heterocyclic ring.
Keywords: pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazines, pyrrolo[2,3-d]pyrimidines, bromolacto-
nization.
Interest in pyrrolo[2,3-d]pyrimidine (7-deazapurine) derivatives increased markedly with the discovery
of the nucleoside antibiotics tubercidin, toyocamycin, and sangivamycin [1-3]. The structural similarity of these
compounds to purine nucleosides is an important stimulus in the search for pyrrolo[2,3-d]pyrimidine series
antiviral preparations. In the course of the last 20 years, the attention of many researchers has been concentrated
on the -D-ribofuranosyl fragment modification and its exchange for carbocyclic or acyclic substituents [4-17].
The mechanism of action of all of the synthesized substances is based on the inhibition of viral DNA
polymerases. A key role in this process is assigned to the hydroxyl group of a cyclic carbohydrate or acyclic
alkyl residue situated near the pyrrole ring nitrogen atom. In this connection the search for methods of synthesis
of novel compounds of this class is certainly a current question. In this work, we propose a method for
preparing pyrrolo[2,3-d]pyrimidines which contain a 3-amino-2-hydroxypropyl substituent at position 7 of the
heterocycle.
It is known that the introduction of vicinal aminoalcohol groups in various heterocyclic systems often
uses a general approach based on the aminolysis of glycidyl derivatives which are obtained from
epichlorohydrin and the corresponding heterocyclic bases [18-20]. We have studied the reaction of methyl
1,3-dimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (1) with 1-chloro-2,3-epoxy-
propane under the conditions reported in the studies [21-26].
Unfortunately, a positive result in that study was not obtained, but it was found that the alkylation of
compound 1 by allyl bromide in DMF in the presence of potassium carbonate gives the methyl 1,3-dimethyl-
2,4-dioxo-7-(2-propenyl)-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidine-6-carboxylate (2) in 45% yield. It
was interesting that the oxidation of the double bond of the 2-propenyl fragment was accompanied by
lactonization to give the pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazine 3 rather than the product 4 expected from
literature data [23, 27, 28]. Undoubtedly, an intramolecular cyclization had become possible due to the
_______
*To whom correspondence should be addressed, e-mail: Smolii@bpci.kiev.ua.
1Institute of Bioorganic and Petroleum Chemistry, Ukraine National Academy of Sciences, 1 Murmanska St.,
Kyiv 02660, Ukraine.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 512-519, March, 2012. Original
article submitted January 28, 2011.
0009-3122/12/4803-0481©2012 Springer Science+Business Media, Inc.
481

O
Me
O
O
N
N
N
O
O
Me
O
Me
O
O Me
O
3
Me
O
H2C
O Me
O
N
HO
OsO4, KClO3
Br
N
O
N
K2CO3
DMF
N
N
N
Me
O
H
O Me
O
Me
N
Me
1
N
CH2
N
2
Me
O
4
favorable positions of the allyl residue and the methoxycarbonyl groups. Hence it was desirable to study a
bromolactonization reaction. This study showed that bromination of the pyrrolo[2,3-d]pyrimidine 2 in
chloroform is accompanied by the formation of a mixture of compounds 5 and 6 which could be separated by
crystallization.
O
O
Me
O
Me
O
O Me
O
N
N
N
N
O
..
N
N
O
Me
Me
+
Br
Br
5
Br2
O
2
O
O Me
O
Me
O
N
Me
O
O Me
O
N
N
N
N
N
Me
+
Me
Br
Br
Br
_
Br
6
The main reaction product is the pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazine 5 obtained in 53% yield.
It should be noted that the only representative of this tricyclic system had been reported by us recently [29]. A
characteristic feature of the structure of compound 5 is the presence in the oxazine lactone fragment of two
electrophilic centers (bromomethyl and carbonyl groups). In this connection it was important to study the
reaction of this product with different nucleophilic reagents. Thus, treatment of compound 5 with thiophenols
and secondary amines gives the products of substitution of the bromine atom in the bromomethyl group for the
nitrogen- and sulfur-containing substituents in compounds 7a,b and 8a,b respectively.
It should also be noted that even prolonged heating of reagent 5 with an excess of the secondary amines
does not lead to opening of the lactone ring whereas treatment of compounds 5, 7, 8 with an excess of primary
aliphatic amines causes cleavage of the oxazine fragment and gives the products 9-11. The composition and
structure of the synthesized compounds were confirmed by elemental analysis and by mass spectrometric, IR,
1
1H and 13C NMR spectroscopic data. Hence the H NMR spectra of the pyrimido[5',4',:4,5]pyrrolo[2,1-c][1,4]-
oxazines 3, 5, 7 show signals for the CH2 group protons as two, one-proton double doublets in the range
482

O
O
Me
O
Me
O
O
O
N
N
R1R2NH
ArSH
5
N
N
N
O
N
O
Me
Me
NR1R2
SAr
7a,b
8a,b
RNH2
MeNH2
O
MeNH2
O
O
H
H
Me
O
Me
O
Me
O
N Me
NHR
O
N Me
N
N
N
N
O
N
N
O
N
N
N
Me
Me
Me
OH
NR1R2
OH
OH
SAr
NHR
9а,b
10a,b
11a,b
7, 9 a NR1R2 =morpholin-4-yl, b NR1R2 = piperidin-1-yl;
8, 11 a Ar = 4-MeC6H4, b Ar = 4-ClC6H4; 10 a R= Me, b R= Pr
TABLE 1. Physicochemical Characteristics of the Synthesized
Compounds 1-3, 5-11
Found, %
——————
Com-
pound
Empirical
formula
Mp*, °С
Yield, %
Calculated, %
С
Н
N
S (Br)
—
C10H11N3O4
50.66
50.63
4.63
4.67
17.80
17.71
298-301
(decomp.)
1
60
45
46
53
15
68
65
75
72
75
64
65
61
91
88
C13H15N3O4
C12H13N3O5
C12H12BrN3O4
C13H15Br2N3O4
C16H20N4O5
C17H22N4O4
C19H19N3O4S
C18H16ClN3O4S
C17H25N5O5
C18H27N5O4
C14H21N5O4
C18H29N5O4
C20H24N4O4S
C19H21ClN4O4S
56.28
56.31
51.65
51.61
42.15
42.13
35.61
35.72
55.12
55.17
59.05
58.95
59.28
59.21
53.33
53.27
53.78
53.82
57.32
57.28
52.05
52.00
57.00
56.98
57.72
57.68
52.28
52.23
5.54
5.45
4.72
4.69
3.50
3.54
3.37
3.46
5.70
5.79
6.37
6.40
5.01
4.97
4.02
3.97
6.59
6.64
7.11
7.21
6.57
6.55
7.73
7.70
5.87
5.81
4.77
4.84
15.10
15.15
14.99
15.05
12.24
12.28
9.57
9.61
16.01
16.08
16.10
16.17
10.99
10.90
10.40
10.35
18.38
18.46
18.48
18.55
21.61
21.66
18.51
18.46
13.52
13.45
12.91
12.82
—
—
169-170
257-259
267-270
218-220
258-261
194-195
160-162
228-230
243-245
223-225
216-218
171-172
202-204
224-226
2
3
23.28
23.35
36.49
36.56
5
6
—
7a
7b
8a
8b
9a
9b
10a
10b
11a
11b
—
8.30
8.32
7.83
7.90
—
—
—
—
7.66
7.70
7.39
7.34
______
*Recrystallization solvents: DMF (compound 1), ethanol (compound 2),
mixture of DMF and ethanol (compounds 3, 5-11).
483

13
4.37-4.96 ppm. A specific feature of the C NMR spectra of compounds 3, 5, 7 is the presence of a signal for
the C-8 carbon atom at 74.7-77.9 ppm. A comparison of spectroscopic properties of the compounds 3, 5, 7 with
the closely structurally related heterocycles synthesized before also pointed to the formation of the 1,4-oxazine
fragment [30]. The presence of the hydroxyl groups in compounds 9-11 which were formed upon opening of the
oxazine ring, was confirmed from the IR and 1H NMR spectra.
Thus a study of the reaction of the substrates with primary aliphatic amines has shown promise for the
use of these compounds in the preparation of pyrrolo[2,3-d]pyrimidines which contain 3-amino-
2-hydroxypropyl substituents in position 7 of the heterocycle.
TABLE 2. 1H NMR Spectra of the Synthesized Compounds 1-3, 5-11
Com-
pound
Chemical shifts, δ, ppm (J, Hz)
3.22 (3H, s, NCH3); 3.49 (3H, s, ОCH3); 3.82 (3H, s, NCH3); 7.07 (1Н, s, Н-7);
12.52 (1H, s, NH)
1
2
3.21 (3H, s, NCH3); 3.64 (3H, s, ОCH3); 3.74 (3H, s, NCH3); 4.70 (1H, d, J = 17.5, CH);
5.16 (1H, d, J = 10.5, CH); 5.33 (2H, s, CH2); 6.08 (1H, dd, J = 10.5, J = 17.5, CH);
7.22 (1Н, s, Н-7)
3.25 (3H, s, NCH3); 3.70-3.72 (5H, m, NCH3, CH2); 4.41 (1H, dd, J = 10.0, J = 13.0) and
4.83 (1H, dd, J = 13.0, J = 3.0, NCH2); 4.69-4.72 (1H, m, CH); 5.29 (1H, t, J = 6.0, ОH);
7.28 (1Н, s, Н-7)
3
5
3.25 (3H, s, NCH3); 3.68 (3H, s, NCH3); 3.84 (1H, dd, J = 11.5, J = 5.5) and
3.92 (1H, dd, J = 11.5, J = 3.5, CH2Br); 4.39 (1H, dd, J = 12.5, J = 10.0) and
4.96 (1H, dd, J = 12.5, J = 2.0, NCH2); 4.98-5.09 (1H, m, CH); 7.31 (1Н, s, Н-7)
3.25 (3H, s, NCH3); 3.74 (3H, s, ОCH3); 3.81 (3H, s, NCH3); 3.99 (2H, d, J = 5.5, CH2Br);
4.69-4.72 (1H, m, CHBr); 5.21-5.25 (2H, m, NCH2); 7.30 (1Н, s, Н-7)
6
2.49 (4H, br. s, 2CH2); 2.69 (2H, d, J = 5.1, CH2); 3.23 (3H, s, NCH3);
3.58 (4H, br. s, 2CH2); 3.70 (3H, s, NCH3); 4.37 (1H, dd, J = 13.0, J = 9.8) and
4.81 (1H, dd, J = 13.0, J = 3.1, NCH2); 4.88-4.92 (1Н, m, СН); 7.27 (1Н, s, Н-7)
7a
1.37-1.39 (2H, m, CH2); 1.48-1.52 (4H, m, 2CH2); 2.44-2.49 (4H, m, 2CH2);
2.62-2.66 (2H, m, CH2); 3.25 (3H, s, NCH3); 3.71 (3H, s, NCH3);
4.37 (1H, dd, J = 13.0, J = 10.0) and 4.78 (1H, dd, J = 13.0, J = 2.6, NCH2);
4.87-4.89 (1Н, m, СН); 7.27 (1Н, s, Н-7)
7b
2.28 (3H, s, CH3); 3.25 (3H, s, NCH3); 3.41-3.44 (2H, m, SCH2); 3.59 (3H, s, NCH3);
4.40-4.43 (1H, m) and 4.84-4.86 (1H, m, CH2); 4.87-4.89 (1H, m, CH);
7.15 (2H, d, J = 8.0, H Ar); 7.29 (1Н, s, Н-7); 7.35 (2H, d, J = 8.0, H Ar)
8a
8b
9a
3.24 (3H, s, NCH3); 3.48-3.51 (2H, m, SCH2); 3.64 (3H, s, NCH3); 4.42-4.45 (1H, m) and
4.88-4.90 (1H, m, CH2); 4.90-4.92 (1H, m, CH); 7.28 (1Н, s, Н-7);
7.38 (2H, d, J = 8.8, H Ar); 7.46 (2H, d, J = 8.8, H Ar)
2.23 (2H, br. s, CH2); 2.34 (4H, br. s, 2CH2); 2.69 (3H, d, J = 4.5, NНCH3);
3.22 (3H, s, NCH3); 3.52 (4H, br. s, 2CH2); 3.74 (3H, s, NCH3); 3.76-3.77 (1H, m, СН);
4.49-4.51 (1H, m, CHН); 4.98-5.02 (2H, m, CНH, ОН); 7.08 (1Н, s, Н-7);
8.21 (1H, br. s, NH)
1.33-1.36 (2H, m, CH2); 1.44-1.47 (4H, m, 2CH2); 2.19-2.21 (2H, m, CH2);
2.34-2.38 (4H, m, 2CH2); 2.71 (3H, d, J = 5.0, NНCH3); 3.23 (3H, s, NCH3);
3.74-3.76 (4H, m, NCH3, СН); 4.51-4.53 (1H, m, CН2) and 4.91-4.93 (2H, m, CН2, ОН);
7.07 (1Н, s, Н-7); 8.25 (1H, br. s, NH)
9b
1.54 (1H, br. s, NH); 2.24 (3H, s, NCH3); 2.38-2.41 (2H, m, CH2);
2.69 (3H, d, J = 4.5, NНCH3); 3.21 (3H, s, NCH3); 3.64-3.67 (1Н, m, СН);
3.73 (3H, s, NCH3); 4.55-4.57 (1Н, m) and 4.86-4.89 (1Н, m, СН2);
5.01 (1Н, br. s, OН); 7.09 (1Н, s, Н-7); 8.24 (1Н, br. s, СОNН)
10a
10b
11a
11b
0.83-0.88 (6H, m, 2CH3); 1.37-1.39 (2H, m, CH2); 1.49-1.52 (2H, m, CH2);
2.42-2.45 (4H, m, 2CH2); 3.10-3.20 (2H, m, CH2); 3.24 (3H, s, NCH3);
3.65-3.68 (1Н, m, СН); 3.76 (3H, s, NCH3); 4.56-4.59 (1Н, m) and
4.89-4.92 (1Н, m, СН2); 5.05 (1Н, br. s, OН); 7.15 (1Н, s, Н-7); 8.31 (1Н, br. s, NН)
2.27 (3H, s, CH3); 2.71 (3H, d, J = 4.5, NНCH3); 2.94-2.99 (2H, m, SCH2);
3.22 (3H, s, NCH3); 3.72-3.74 (4H, m, NCH3, СН); 4.58-4.60 (1Н, m) and
5.07-5.09 (1Н, m, СН2); 5.45 (1Н, d, J = 5.5, OН); 7.10 (2Н, d, J = 8.0, H Ar);
7.12 (1Н, s, Н-7); 7.22 (2H, d, J = 8.0, H Ar); 8.27 (1Н, br. s, NН)
2.71 (3H, d, J = 4.0, NНCH3); 2.94-3.07 (2H, m, SCH2); 3.23 (3H, s, NCH3);
3.73-3.75 (4H, m, NCH3, СН); 4.60-4.62 (1Н, m) and 5.04-5.08 (1Н, m, СН2);
5.52 (1Н, d, J = 5.5, OН); 7.13 (1Н, s, Н-7); 7.35 (4Н, br. s, H Ar); 8.26 (1Н, br. s, NН)
484

EXPERIMENTAL
1
IR spectra were recorded on a Bruker Vertex 70 FTIR instrument using KBr pellets. H and 13C NMR
spectra were recorded on Varian VXR-300 (300 MHz) (compound 7a), Varian Mercury-400 (400 MHz)
(compounds 7b, 8b), and Bruker Avance 500 instruments (500 MHz and 125 MHz, respectively) (compounds
1-6, 8a, 9-11) using DMSO-d6 with TMS as internal standard. Chromato-mass spectra were recorded on an
Agilent 1100 LC/MSD VL spectrometer using APCI (atmospheric pressure positive chemical ionization).
Monitoring of the reaction progress and purity of the compounds obtained was performed by TLC on Silufol
UV-254 plates and revealed using UV light.
The starting methyl 1,3-dimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidine-6-carb-
oxylate (1) was prepared using the method [31].
Methyl 1,3-Dimethyl-2,4-dioxo-7-(prop-2-en-1-yl)-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidine-
6-carboxylate (2). Allyl bromide (15 mmol) was added with stirring to a suspension of compound 1 (2.37 g,
10 mmol) and K2CO3 (2.8 g, 20.2 mmol) in DMF (50 ml). The mixture was heated for 6 h at 75ºC, cooled, and
diluted with water (50 ml). The product was extracted with chloroform (325 ml), solvent evaporated in vacuo,
and the residue was recrystallized.
8-Hydroxymethyl-1,3-dimethyl-8,9-dihydro-2H-pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazine-
2,4,6(1H,3H)-trione (3). A mixture of the pyrrolo[2,3-d]pyrimidine 2 (0.5 g, 11.8 mmol), KClO3 (0.3 g), and
OsO4 (10 mg, 0.04 mmol) in 1:1 aqueous MeOH (20 ml) was refluxed for 12 h. The precipitate formed was
filtered off and purified by crystallization. IR spectrum, , cm-1: 1559 (C=O), 1656 (C=O), 1697 (C=O), 3404
(OH). 13C NMR spectrum, , ppm: 158.6 (6-C=O); 158.3 (2-C=O); 151.7 (4-C=O); 139.6 (C-10a); 117.8
(C-5a); 113.2 (C-5); 102.4 (C-4a); 77.9 (C-8); 60.9 (C-9); 45.0 (CH2OH); 32.1 (NCH3); 28.5 (NCH3).
Bromination of the Pyrrolo[2,3-d]pyrimidine 2. Bromine (1.86 ml, 36.0 mmol) in chloroform (5 ml)
was added dropwise with stirring to a suspension of the pyrrolo[2,3-d]pyrimidine 2 (5.0 g, 18.0 mmol) in
chloroform (25 ml). The mixture was heated at 50ºC until became homogeneous. The mixture was cooled and
the oily residue was separated by decantation, diluted with EtOH (20 ml), and held for 10 min at 70-80ºC. The
precipitate formed was filtered off and purified by crystallization (compound 5 ). The solvent after decantation
was evaporated in vacuo and the residue obtained was refluxed for 5 min in EtOH (20 ml). The precipitate
formed was filtered off and purified by crystallization (compound 6).
8-Bromomethyl-1,3-dimethyl-8,9-dihydro-2H-pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazino-
13
2,4,6(1H,3H)-trione (5). IR spectrum, , cm-1: 1557 (C=O), 1660 (C=O), 1690 (C=O). C NMR spectrum, ,
ppm: 158.9 (2-C=O); 158.3 (6-C=O); 151.6 (4-C=O); 139.8 (C-10a); 117.4 (C-5a); 113.7 (C-5); 102.3 (C-4a);
75.5 (C-8); 46.4 (C-9); 32.2 (CH2Br); 32.1 (NCH3); 28.5 (NCH3). Mass spectrum, m/z: 344/342 (81Br/79Br)
[M+H]+ (100).
Methyl 7-(2,3-Dibromopropyl)-1,3-dimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimi-
dine-6-carboxylate (6). 13C NMR spectrum, , ppm: 161.0 (O–C=O); 158.3 (2-C=O); 152.3 (4-C=O); 143.5
(C-8); 121.9 (C-6); 115.5 (C-5); 101.6 (C-9); 53.1 (CHBr); 52.3 (OCH3); 50.7 (NCH2); 35.9 (CH2Br); 33.8
(NCH3); 28.6 (NCH3).
1,3-Dimethyl-8-(morpholin-4-ylmethyl)-8,9-dihydro-2H-pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxa-
zino-2,4,6(1H,3H)-trione (7a). A mixture of compound 5 (0.34 g, 1 mmol) and morpholine (0.26 g, 3 mmol)
was heated for 5 h at 110-120ºC, cooled, and diluted with EtOH (10 ml). The mixture was left for 3-4 h at room
temperature and the precipitate formed was filtered off and purified by crystallization. IR spectrum, , cm-1:
1685 (C=O); 1689 (C=O); 1726 (C=O). 13C NMR spectrum, , ppm: 157.9 (6-C=O); 157.8 (2-C=O); 151.2
(4-C=O); 139.5 (C-10a); 117.3 (C-5a); 112.7 (C-5); 101.9 (C-4a); 74.7 (C-8); 58.6 (C-9); 45.7 (C-11); 31.6
(NCH3); 28.0 (NCH3); 66.1 (O(CH2)2); 53.7 (N(CH2)2). Mass spectrum, m/z: 349 [M+H]+ (100).
1,3-Dimethyl-8-(piperidin-1-ylmethyl)-8,9-dihydro-2H-pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxa-
zino-2,4,6(1H,3H)-trione (7b) was prepared similarly. 13C NMR spectrum, , ppm: 158.5 (6-C=O); 158.3
(2-C=O); 151.7 (4-C=O); 139.6 (C-10a); 117.9 (C-5a); 113.2 (C-5); 102.4 (C-4a); 75.5 (C-8); 59.5 (C-9);
485

55.1 (N(CH2)2); 46.3 (C-11); 39.6 (NCH3); 32.2 (NCH3); 28.5 ((CH2)2); 26.1 (CH2). Mass spectrum, m/z: 347
[M+H]+ (100).
8-[(Arylsulfanyl)methyl]-1,3-dimethyl-8,9-dihydro-2H-pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxa-
zino-2,4,6(1H,3H)-triones 8a,b (General Method). A mixture of compound 5 (0.34 g, 1.0 mmol), the
corresponding thiophenol (1.1 mmol), and Et3N (1.1 mmol) in MeCN (10 ml) was refluxed for 2 h. The mixture
was left for 3-4 h at room temperature and the precipitate formed was filtered off and purified by
recrystallization.
1,3-Dimethyl-8-[(4-methylphenylsulfanyl)methyl]-8,9-dihydro-2H-pyrimido[5',4':4,5]pyrrolo[2,1-c]-
[1,4]oxazino-2,4,6(1H,3H)-trione (8a). IR spectrum, , cm-1: 1664 (C=O), 1695 (C=O), 1722 (C=O).
Reaction of the Pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazines 5, 7a,b, 8a,b with Methylamine
(General Method). A mixture of one of the pyrimido[5',4':4,5][pyrrolo[2,1-c][1,4]oxazines 5, 7a,b, 8a,b
(0.8 mmol) and MeNH2 (4.0 mmol) in MeOH (10 ml) was refluxed for 3 h, and the precipitate formed was
filtered off and purified by crystallization.
7-[Hydroxy-3-(morpholin-4-yl)propyl]-N,1,3-trimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo-
[2,3-d]pyrimidine-6-carboxamide (9a). IR spectrum, , cm-1: 1551 (C=O), 1653 (C=O), 1687 (C=O), 3301
(NH), 3406 (OH). Mass spectrum, m/z: 380 [M+H]+ (100).
7-[2-Hydroxy-3-(methylamino)propyl]-N,1,3-trimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo-
[2,3-d]pyrimidine-6-carboxamide (10a). IR spectrum, , cm-1: 1645 (br., C=O), 1705 (C=O), 2929-3101
(NH), 3294 (NH), 3395 (OH).
7-{2-Hydroxy-3-[(4-methylphenyl)sulfanyl]propyl}-N,1,3-trimethyl-2,4-dioxo-2,3,4,7-tetrahydro-
1H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (11a). IR spectrum, , cm-1: 1650 (br., C=O), 1703 (C=O), 3393
(NH), 3453 (OH).
7-{-3-[(4-Chlorophenyl)sulfanyl-2-hydroxy]propyl}-N,1,3-trimethyl-2,4-dioxo-2,3,4,7-tetrahydro-
1H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (11b). IR spectrum, , cm-1: 1649 (br., C=O), 1702 (C=O), 3392
(NH), 3442 (OH).
7-[2-Hydroxy-3-(propylamino)propyl]-N,1,3-trimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo-
[2,3-d]pyrimidine-6-carboxamide (10b). A mixture of compound 5 (0.34 g, 1 mmol) and propylamine
(5 mmol) was refluxed for 5 h and the precipitate formed was filtered off and purified by crystallization. IR
spectrum, , cm-1: 1651 (br., C=O), 1698 (C=O), 2960-3100 (NH), 3310 (NH); 3396 (OH).
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