Study on the reaction of methyl N-methyl-N-(6-substituted-5-nitropyrimidin- 4-yl)glycinates with sodium alkoxides

Article abstract of DOI:10.1002/jhet.5570430205

Methyl N-methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates (4a-n), obtained from 6-substituted-4-chloro-5-nitropyrimidines and sarcosine methyl ester (methyl 2-(methylamino)acetate), in the reaction with sodium alkoxides underwent transformations t

Full text of DOI:10.1002/jhet.5570430205

Mar-Apr 2006
267
Study on the Reaction of Methyl N-Methyl-N-(6-substituted-5-
nitropyrimidin-4-yl)glycinates with Sodium Alkoxides
Inga Susvilo, Algirdas Brukstus and Sigitas Tumkevicius*
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24,
LT-03225 Vilnius, Lithuania
Received May 6, 2005
Methyl N-methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates (4a-n), obtained from 6-substituted-
4-chloro-5-nitropyrimidines and sarcosine methyl ester (methyl 2-(methylamino)acetate), in the reaction
with sodium alkoxides underwent transformations to give different products. N-methyl-N-(5-
nitropyrimidin-4-yl)glycinates (4a,i,j) bearing amino and arylamino groups in the position 6 of the
pyrimidine ring gave corresponding 6-substituted-4-methylamino-5-nitrosopyrimidines (5a,i,j). In the
reaction of N-(6-alkylamino-5-nitropyrimidin-4-yl)-N-methylglycinates (4b,f-h) with sodium alkoxides the
corresponding 6-alkylamino-4-methylamino-5-nitrosopyrimidines (5b,f-h) and 5-hydroxy-8-methyl-5,8-
dihydropteridine-6,7-diones (6b,f-h) were formed. The main products of the reaction of N-(6-
dialkylamino-5-nitropyrimidin-4-yl)-N-methylglycinates (4c-e,k,l), after work-up, were the corresponding
6-dialkylamino-9-methylpurin-8-ones (7c-e,k,l) and 8-alkoxy-6-dialkylamino-9-methylpurines (9c,l,
10c,l). Methyl N-methyl-N-{[6-(2-methoxy-oxoethyl)thio]-5-nitropyrimidin-4-yl}glycinate (4n) under the
same conditions gave methyl 7-methylaminothiazolo[5,4-d]pyrimidine-2-carboxylate (13). Mechanisms of
the observed transformations are discussed.
J. Heterocyclic Chem., 43, 267 (2006).
Introduction.
6-substituted 4-chloro-5-nitropyrimidines (1, 3a-e)
[10-13] were used as starting materials. Substitution
of one chlorine atom in 1 with sarcosine methyl ester
was achieved at 5° to give 2 in 91 % yield.
6-Substituted 4-chloro-5-nitropyrimidines (3a-e)
reacted with sarcosine methyl ester at reflux
temperature of methanol to give the corresponding
Nitropyrimidines due to versatility of the nitro group are
often used for the synthesis of various types of heterocyclic
compounds [1-4]. However transformations of 5-nitro-
pyrimidines under basic non-reductive conditions are still
studied insufficiently. Literature survey on these reactions
reveals only few reports on the cyclisation reactions of 5-
nitropyrimidines, bearing an active methyleneamino group
in position 4 of the pyrimidine ring. For example, 5-nitro-4-
phenacylaminopyrimidines in aqueous sodium hydroxide
solution were shown to undergo a cyclocondensation
reaction with the formation of 9H-purine-7-oxides [5-8].
Recently in our preliminary report [9] it has been shown
that methyl N-methyl-N-(6-substituted-5-nitropyrimidin-4-
yl)glycinates on treatment with sodium alkoxides undergo
transformations into 6-substituted 4-methylamino-5-
nitrosopyrimidines 5 or 9-methylpurin-8-ones 7. Now we
report on more detail and extensive study on these
transformations.
Results and Discussion.
For the synthesis of methyl N-methyl-N-(5-
nitropyrimidin-4-yl)glycinates (4a-n) readily available

268
I. Susvilo, A. Brukstus and S. Tumkevicius
Vol 43
N-methyl-N-(pyrimidin-4-yl)glycinates 4a-e. Analogously,
reaction of methyl N-methyl-N-(6-chloro-5-nitropyrim-
idin-4-yl)glycinate (2) with selected amines or sodium
salts of methyl mercaptoacetate or thiophenol, prepared in
situ, furnished compounds 4f-n (Scheme 1).
The reactions of the title compounds 4a-n with sodium
alkoxides in alcohols (methanol, ethanol, propanol) reveal
a variety of behavior depending on the nature of
substituent in position 6 of the pyrimidine ring. (Figure 1,
Table 1). It should be noted that all reactions were carried
out under the same reaction conditions: room temperature
and an equivalent amount of the appropriate sodium
alkoxide was used.
Compounds 4a,i,j bearing primary amino or arylamino
groups in position 6 of the pyrimidine ring in the reaction
with alkoxides afforded the corresponding 6-substituted-
4-methylamino-5-nitrosopyrimidines (5a,i,j) as the only
products. However reaction of 6-alkylamino derivatives
4b,f-h with sodium alkoxides gave a mixture of 5-
nitrosopyrimidines 5b,f-h and sodium salts of 8-methyl-5-
hydroxypteridine-6,7-diones 6b,f-h in yields higher for
the latter compounds (Table 1). Similar behavior also
showed 6-phenylthio derivative 4m. Its reaction with
sodium methoxide gave the corresponding 8-methyl-5-
hydroxypteridine-6,7-dione 6m as the main product
Table 1
Products from the reactions of methyl N-methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates (4a-n) with sodium alkoxides.
Comp.
R
Base
Yields (%) [a]
5
6
-
7
-
Others
-
4a
4a
4a
4b
4c
NH2
NH2
NH2
MeNH
Me2N
NaOMe
NaOEt
NaOPr
NaOMe
NaOMe
60
55
49
15
-
52
-
-
-
25 [b]
8c (25%),
9c (31%)
8c (27%),
10c (3%)
-
4c
Me2N
NaOEt
-
-
27 [b]
4c
4d
4e
4e
4e
4f
4g
4g
4g
4h
4i
4i
4i
4j
4j
4j
4k
4l
4l
4l
Me2N
(CH2)4N
(CH2)6N
(CH2)6N
(CH2)6N
PrNH
PhCH2NH
PhCH2NH
PhCH2NH
Ph(CH2)2NH
PhNH
NaOPr
NaOMe
NaOMe
NaOEt
NaOPr
NaOMe
NaOMe
NaOEt
NaOPr
NaOMe
NaOMe
NaOEt
NaOPr
NaOMe
NaOEt
NaOPr
NaOMe
NaOMe
NaOEt
NaOPr
NaOMe
NaOPr
NaOMe
NaOEt
NaOPr
-
-
-
-
-
-
80
33 [b]
52
8d (33%)
-
55
50
-
8
48
48
45
30
54
-
-
-
30
24
20
32
65
58
49
85
79
60
-
-
-
-
-
-
PhNH
PhNH
3-CF3-C6H4NH
3-CF3-C6H4NH
3-CF3-C6H4NH
MeNCH2CO2Me
PhNMe
-
-
-
-
-
64
55
42
28
-
-
9l (31%)
10l (4%)
-
PhNMe
PhNMe
PhS
PhS
SCH2CO2Me
SCH2CO2Me
SCH2CO2Me
4m
4m
4n
4n
4n
-
-
-
44
30
-
traces 11m (3%), 12 (5%)
-
-
-
13 (78%)
13 (40%)
13 (35%)
[a] Yields after isolation of products; [b] obtained after acidification of salts 8c,d.

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Methyl N-Methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates
269
(Table 1). However, traces of purin-8-one 7m, 6-
phenylthio-9-methyl-9H-purine 7-oxide (11m) and 6-
methoxy-4-methylamino-5-nitrosopyrimidine (12) (Table
1, Figure 2) were isolated from the reaction mixture using
dry column vacuum chromatography [14]. Compound 12
is possibly formed from nitrosopyrimidine 5m during
nucleophilic substitution reaction of the phenylthio group
with sodium methoxide. The reaction of 4m with sodium
propoxide gave only 5-hydroxy-8-methyl-4-phenylthio-
5,8-dihydropteridine-6,7-dione (6m) as well as unreacted
4m. Structure of 4-methylamino-5-nitrosopyrimidines 5
was unambiguously proved using single crystal X-ray
diffraction analysis [9] and NMR spectroscopy. It should
be mentioned that 6-amino-, 6-alkylamino and 6-
arylamino-4-methylamino-5-nitrosopyrimidines (5a,b,g-j)
in solutions exist as a mixture of two conformers [9] and
could be in an equilibrium with their aci-forms I
stabilised by the primary or secondary amino groups in
position 6 of the pyrimidine ring (Scheme 3). This allows
to form the pyrimido[4,5-e][2,1,4]oxadiazine intermediate
II. When R is H or aryl, O-Hb bond becomes more polar
due to stronger hydrogen bond between Ha and oxygen of
the nitro group and ring opening of the oxadiazine II
occurs preferably by an attack of a base on Hb (route i) to
form intermediate III leading to the nitroso derivatives 5
after elimination of OHCCO2Me. When R is alkyl an
acidity of Hb should be lower than in previous case.
Therefore ring opening of oxadiazine II is realised by
competitive abstraction of either Hb (route i) or Hc (route
ii) and formation of a mixture of nitrosopyrimidines 5 and
pteridine-5,8-diones 6 is observed.
On the other hand, formation of nitrosopyrimidines
5 by a competitive mechanism via methyl purine-6-
carboxylate 7-oxides IV (route iii) must be also
considered. Isolation of purine 7-oxide 11m in the
reaction of 4m with sodium methoxide and data of the
analogous reactions of methyl N-(6-dialkylamino-5-
nitropyrimidin-4-yl)-N-methylglycinates (4c-e,k,l) (see
below) confirm that Dieckmann’s type cyclocondensation
of methyl N-(5-nitropyrimidin-4-yl)-N-methylglycinates 4
can occur in some cases. Then addition of hydroxide to
IV causes the imidazole ring opening to give intermediate
III. The preference for a hydroxide ion to attack C8 of
purine IV is probably determined by the increased
reactivity of C8 towards nucleophiles due to the
interaction of substituent in position 6 of the purine with
the oxygen of the 7-oxide group.
1
two sets of signals are observed in their H NMR spectra
(see Experimental).
Reaction of compound 4n bearing SCH2CO2Me
substituent in position 6 of the pyrimidine ring reacted
with sodium alkoxides to give methyl 7-methylaminothi-
azolo[5,4-d]pyrimidine-2-carboxylate (13) as the only
reaction product (Scheme 2). The reaction outcome could
be explained by the formation of nitroso derivative 5n and
subsequent intramolecular cyclisation reaction between
the nitroso and SCH2 groups to form thiazolo[5,4-d]-
pyrimidine 13.
Neither 5-nitrosopyrimidines 5 nor 5-hydroxy-8-methyl-
5,8-dihydropteridine-6,7-diones 6 formed in the reaction
of methyl N-(6-dialkylamino-5-nitropyrimidin-4-yl)-N-
methylglycinates (4c-e,k,l) with sodium alkoxides. 6-
Dimethylamino derivative 4c in the reaction with sodium
Results obtained for the reactions of methyl N-[6-
amino-, 6-alkylamino-, 6-arylamino-, or 6-(substituted
thio)-5-nitropyrimidin-4-yl]-N-methylglycinates (4a,b,f-
j,m,n) with sodium alkoxides could be rationalised by a
following mechanism. According to the data obtained in
the investigation of transformations of o-nitrophenyl-
glycine esters [15-17] nitro compounds in basic media
methoxide or ethoxide gave a mixture of two products –
sodium salt of purine-8-carboxylic acid 7-oxide 8c and the
corresponding 8-alkoxy-6-dimethylamino-9-methylpurines
(9c or 10c) (Figure 1, Table 1). It is noteworthy, that in the
reaction of 4c with sodium propoxide, as well as of 4e and
4k with other sodium alkoxides purinones 7c, 7e and 7k
were formed as the only reaction products. Reaction of

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I. Susvilo, A. Brukstus and S. Tumkevicius
Vol 43
compound 4l with sodium methoxide or ethoxide led to a
mixture of purin-8-one 7l and 8-alkoxypurines 9l, 10l,
respectively. Compound 4d with sodium methoxide gave
sodium salt of purine-8-carboxylic acid 7-oxide 8d as the
sole product. In order to obtain carboxylic acids 14 sodium
salts 8c,d were acidified with hydrochloric acid. However,
compounds 8c,d underwent spontaneous decarboxylation
and products formed appeared to be purin-8-ones 7c,d but
not expected purin-7-oxides 11c,d. Structure of 7c,
obtained after acidification of salt 8c, was confirmed by X-
ray analysis. The crystallografic data of 7c indicated that
this compound was obtained as hydrochloride: protonation
occurred at N1 atom of the purine system (Figure 3).
Nevertheless, acidification of 8d at 0° allowed to obtain
the corresponding carboxylic acid 14d. However, due its
instability, it was impossible to characterise 14d and to
record its nmr spectra. Already during dissolving 14d in
dimethylsulfoxide-d6 spontaneous decarboxylation was
observed and the 1H-nmr spectrum of the sample
contained signals of purine 7-oxide 11d (d 1.99 (t, J = 4.8
Hz, 4H, (CH2)2), 3.61 (t, J = 4.8 Hz, 4H, N(CH2)2), 3.66
(s, 3H, NMe), 8.14 (s, 1H, C2-H), 8.63 (s, 1H, C8-H)) and
1
purin-8-one 7d (see Experimental) in a ratio 7:3. The H-
nmr spectrum recorded after sample’s heating contained
only the signals of compound 7d. Purinone 7d was also
obtained by heating of crude carboxylic acid 14d in
anhydrous xylene.
Formation of purine-8-carboxylic acid 7-oxides and
their conversion into purin-8-ones indicates that
Dieckmann’s type cyclocondensation of 6-dialkylamino
derivatives occurs in the first step of rearrangement
(Scheme 4). Due to steric hindrance of 6-dialkylamino
groups realisation of aci-forms I of 4c-e,k,l fails. Nitro
group turns out of a plane of the pyrimidine ring and it
makes Dieckmann’s reaction to become more favorable.
Then attack of the hydroxide ion takes place at the ester
carbonyl of IV to form purine 7-oxides 11c-e,k,l,m.
Finally, purine 7-oxides 11 undergo rearrangement to give
Figure 3. Ortep drawing of compound 7c.

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Methyl N-Methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates
271
purine-8-ones 7c-e or corresponding 8-alkoxypurines 9c,l,
10c,l.
In summary, the present investigation provides novel
results on chemistry of 5-nitropyrimidines. It was found
that alkoxide-induced transformations of the title com-
pounds give products, whose formation is sometimes
difficult to predict. Nevertheless, the data obtained allow
to conclude that main products of the reaction of N-
methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates
(4a,i,j) bearing amino or arylamino groups in the position
6 are 6-substituted-4-methylamino-5-nitrosopyrimidines
5a,i,j. Reaction of N-(6-alkylamino-5-nitropyrimidin-4-
Taking into account that formation of 9-methylpurin-8-
ones 7 proceeds in protic and anhydrous conditions
rearrangement of purine 7-oxides 11 into purin-8-ones 7
possibly occurs by competitive mechanisms of an
abnormal addition-elimination process of water (AEa)
(intermediate 15) or bimolecular intermediate 16, similar
to that proposed for conversion of benzimidazole
N-oxides [18].

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Vol 43
Methyl N-Methyl-N-(6-methylamino-5-nitropyrimidin-4-yl)-
glycinate (4b).
yl)-N-methylglycinates (4b,f-h) leads to a mixture of the
corresponding
6-alkylamino-4-methylamino-5-nitroso-
pyrimidines (5b,f-h) and 4-alkylamino-5-hydroxy-8-
methyl-5,8-dihydropteridine-6,7-diones (6b,f-h). The
main products of interaction of N-(6-dialkylamino-5-
nitropyrimidin-4-yl)-N-methylglycinates (4c-e,k,l) with
sodium alkoxides in the appropriate alcohols, after work-
up, were found to be the corresponding 6-dialkylamino-9-
methylpurin-8-ones (7c-e,k,l) and 8-alkoxy-6-dialkyl-
amino-9-methylpurines (9c,l, 10c,l).
This compound was obtained as a yellow solid, mp 82-82.5°
(from methanol); yield 51%; ir (KBr): 3351 (NH), 1746 (CO)
1
cm-1; H nmr (acetone-d6): ꢀ 2.91 (s, 3H, NMe), 3.13 (d, J = 4.8
Hz, 3H, NHMe), 3.74 (s, 3H, OMe), 4.45 (s, 2H, NCH2), 8.05 (s,
1H, C2-H), 8.31 (br.s, 1H, NH).
Anal. Calcd. for C9H13N5O4: C, 42.35; H, 5.13; N, 27.44.
Found: C, 42.18; H, 4.99; N, 27.35.
Methyl N-Methyl-N-(6-dimethylamino-5-nitropyrimidin-4-yl)-
glycinate (4c).
This compound was obtained as a yellow solid, mp 63-64°
(from 2-propanol); yield 98%; ir (KBr): 1748 (CO) cm-1; 1H nmr
(deuteriochloroform): ꢀ 3.23 (s, 3H, NMe), 3.24 (s, 6H, NMe2),
3.80 (s, 3H, OMe), 4.37 (s, 2H, NCH2), 7.91 (s, 1H, C2-H).
Anal. Calcd. for C10H15N5O4: C, 44.61; H, 5.62; N, 26.01.
Found: C, 44.69; H, 5.86; N, 26.20.
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. IR spectra were run in Nujol mulls or in KBr discs
on a Perkin-Elmer FT spectrophotometer Spectrum BX II. H
1
nmr spectra were recorded with a Varian Unity spectrometer
(300 MHz) using tetramethylsilane as internal standard. Mass
spectra were performed using direct insertion probe on a Kratos
MS-30 spectrometer (70 eV). Elemental analyses (C, N, H)
results were found to be in good agreement (±0.4%) with the
calculated values. All reactions and purity of the synthesised
compounds were monitored by TLC using Silica gel 60 F254
aluminium plates (Merck). Visualization was accomplished by
UV light.
Methyl N-Methyl-N-(6-pyrrolidino-5-nitropyrimidin-4-yl)-
glycinate (4d).
This compound was obtained as a yellow solid, mp 86-87°
(from 2-propanol); yield 65%; ir (KBr): 1748 (CO) cm-1; 1H nmr
(acetone-d6): ꢀ 1.98-2.03 (m, 4H, (CH2)2), 3.16 (s, 3H, NMe),
3.54-3.59 (m, 4H, N(CH2)2), 3.73 (s, 3H, OMe), 4.40 (s, 2H,
NCH2), 7.94 (s, 1H, C2-H).
Anal. Calcd. for C12H17N5O4: C, 48.81; H, 5.80; N, 23.72.
Found: C, 48.98; H, 5.76; N, 23.85.
Methyl N-(6-chloro-5-nitropyrimidin-4-yl)-N-methylglycinate
(2).
Methyl N-[6-(Azepan-1-yl)-5-nitropyrimidin-4-yl]-N-methyl-
glycinate (4e).
To a cooled to 5 °C suspension of compound 1 [10] (5 g, 26
mmol) and sarcosine methyl ester hydrochloride [19] (3.6 g, 26
mmol) in chloroform (15 ml) a solution of triethylamine (5.2 g,
52 mmol) in chloroform (10 ml) was added dropwise. The
reaction mixture was stirred at 5° for 30 min. Then the solution
was washed with water, organic layer dried with Na2SO4 and
evaporated under reduced pressure to dryness. The residue was
recrystallised to give 6.2 g (91%) of compound 2, mp 45-46°
(from hexane); ir (nujol): 1762 (CO) cm-1; 1H nmr
(deuteriochloroform): ꢀ 3.07 (s, 3H, NMe), 3.78 (s, 3H, OMe),
4.38 (s, 2H, NCH2), 8.37 (s, 1H, C2-H).
This compound was obtained as a yellow solid, mp 97-98°
(from 2-propanol); yield 57%; ir (KBr): 1749 (CO) cm-1; 1H nmr
(deuteriochloroform): ꢀ 1.39-1.89 (m, 8H, (CH2)4), 3.27 (s, 3H,
NMe), 3.49-3.67 (m, 4H, N(CH2)2), 3.80 (s, 3H, OMe), 4.36 (s,
2H, NCH2), 7.91 (s, 1H, C2-H).
Anal. Calcd. for C14H21N5O4: C, 52.00; H, 6.55; N, 21.66.
Found: C, 51.95; H, 6.70; N, 21.82.
General Procedure for the Synthesis of Methyl N-Methyl-N-(6-
substituted-5-nitropyrimidin-4-yl)glycinates (4f-n).
Anal. Calcd. for C8H9ClN4O4: C, 36.87; H, 3.48; N, 21.50.
Found: C, 36.98; H, 3.46; N, 21.39.
To a solution of compound 2 (2 g, 7.66 mmol) in methanol
(20 ml) a solution of the corresponding amine (15.32 mmol) or
sodium salt of methyl mercaptoacetate, prepared from sodium
(0.176 g, 7.66 mmol), anhydrous methanol (3 ml) and methyl
mercaptoacetate (0.81 g, 7.66 mmol), or sodium salt of
thiophenol, prepared from sodium (0.176 g, 7.66 mmol),
anhydrous methanol (3 ml) and thiophenol (0.84 g, 7.66 mmol),
was added. The reaction mixture was refluxed for 15 min. After
cooling to room temperature the precipitate was collected by
filtration, washed with water and recrystallised to give
compounds 4f-n.
General Procedure for the Synthesis of Methyl N-(6-Substituted-
5-nitropyrimidin-4-yl)-N-methylglycinates (4a-e).
A solution of compounds 3a-e (10 mmol), sarcosine methyl
ester hydrochloride (1.4 g, 10 mmol), triethylamine (2.02 g, 20
mmol) in methanol (20 ml) was refluxed for 30 min. The solvent
was evaporated under reduced pressure to dryness, the residue was
washed with water and recrystallised to give compounds 4a-e.
Methyl N-(6-Amino-5-nitropyrimidin-4-yl)-N-methylglycinate
(4a).
Methyl N-Methyl-N-(6-propylamino-5-nitropyrimidin-4-yl)-
glycinate (4f).
This compound was obtained as a yellow solid, mp 143-145°
(from methanol); yield 66%; ir (nujol): 3462, 3431 (NH2), 1754
This compound was obtained as a yellow solid, mp 85-86°
(from hexane); yield 95%; ir (KBr): 3398 (NH), 1752 (CO) cm-1;
1H nmr (acetone-d6): ꢀ 0.99 (t, J = 7.5 Hz, 3H, Me), 1.66-1.75
(m, J = 7.5 Hz, 2H, CH2), 2.98 (s, 3H, NMe), 3.61 (q, J = 7.5
Hz, 2H, NHCH2), 3.74 (s, 3H, OMe), 4.45 (s, 2H, NCH2), 8.03
(s, 1H, C2-H), 8.31 (br.s, 1H, NH).
1
(CO) cm-1; H nmr (deuteriochloroform): ꢀ 2.97 (s, 3H, NMe),
3.78 (s, 3H, OMe), 4.34 (s, 2H, NCH2), 7.00 (br.s, 2H, NH2),
7.97 (s, 1H, C2-H).
Anal. Calcd. for C8H11N5O4: C, 39.84; H, 4.60; N, 29.04.
Found: C, 40.00; H, 4.65; N, 29.11.

Mar-Apr 2006
Methyl N-Methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates
273
Anal. Calcd. for C11H17N5O4: C, 46.64; H, 6.05; N, 24.72.
Found: C, 46.58; H, 5.99; N, 24.65.
Anal. Calcd. for C15H17N5O4: C, 54.38; H, 5.17; N, 21.14.
Found: C, 54.44; H, 4.99; N, 21.09.
Methyl N-(6-Benzylamino-5-nitropyrimidin-4-yl)-N-methyl-
glycinate (4g).
Methyl N-Methyl-N-(5-nitro-6-phenylthiopyrimidin-4-yl)-
glycinate (4m).
This compound was obtained as a yellow solid, mp 102-
102.5° (from 2-propanol); yield 67%; ir (Nujol): 3332 (NH),
1744 (CO) cm-1; 1H nmr (acetone-d6): ꢀ 2.98 (s, 3H, NMe), 3.73
(s, 3H, OMe), 4.44 (s, 2H, NCH2), 4.88 (d, J = 6 Hz, 2H,
NHCH2), 7.28 – 7.44 (m, 5H, ArH), 8.03 (s, 1H, C2-H), 8.71
(br.s, 1H, NH).
This compound was obtained as a yellow solid, mp 105-107°
(from 2-propanol); yield 66%; ir (KBr): 1746 (CO) cm-1; 1H nmr
(deuteriochloroform): ꢀ 3.03 (s, 3H, NMe), 3.80 (s, 3H, OMe),
4.40 (s, 2H, NCH2), 7.46 – 7.90 (m, 5H, ArH), 8.19 (s, 1H, C2-
H),
Anal. Calcd. for C14H14N4O4S: C, 50.29; H, 4.22; N, 16.76.
Found: C, 50.17; H, 4.35; N, 16.63.
Anal. Calcd. for C15H17N5O4: C, 54.38; H, 5.17; N, 21.14.
Found: C, 54.58; H, 5.23; N, 21.07.
Methyl N-{6-[(2-Methoxy-2-oxoethyl)thio]-5-nitropyrimidin-4-
yl}-N-methylglycinate (4n).
Methyl N-Methyl-N-{6-[(2-phenylethyl)amino]-5-nitropyrim-
idin-4-yl}glycinate (4h).
This compound was obtained as a yellow solid, mp 129-130°
(from methanol); yield 71%; ir (KBr): 1754, 1735 (CO) cm-1;
1H nmr (acetone-d6): ꢀ 3.03 (s, 3H, NMe), 3.71 (s, 3H, OMe),
3.74 (s, 3H, OMe), 4.06 (s, 2H, SCH2), 4.54 (s, 2H, NCH2), 8.35
(s, 1H, C2-H).
This compound was obtained as a yellow solid, mp 100-101°
(from ethanol); yield 94%; ir (KBr): 3379 (NH), 1749 (CO)
1
cm-1; H nmr (dichloromethane-d2): ꢀ 2.96 (s, 3H, NMe), 2.99
(t, J = 7.2 Hz, 2H, CH2), 3.79 (s, 3H, OMe), 3.88 (q, J = 7.2 Hz,
2H, NHCH2), 4.36 (s, 2H, NCH2), 7.29 – 7.46 (m, 5H, ArH),
8.08 (s, 1H, C2-H), 8.23 (br.s, 1H, NH).
Anal. Calcd. for C11H14N4O6S: C, 40.00; H, 4.27; N, 16.96.
Found: C, 40.32; H, 4.39; N, 16.75.
Anal. Calcd. for C16H19N5O4: C, 55.64; H, 5.55; N, 20.28.
Found: C, 55.77; H, 5.43; N, 20.04.
General Procedure for the Synthesis of Compounds 5-13.
To a suspension of the corresponding compound 4a-n (5
mmol) in an alcohol (methanol, ethanol, propanol) (5 ml) a
solution of the sodium alkoxide, prepared from sodium (0.115 g,
5 mmol) and appropriate alcohol (3 ml), was added dropwise
under stirring. The reaction mixture was stirred at room
temperature for 2 h.
Methyl N-(6-Anilino-5-nitropyrimidin-4-yl)-N-methylglycinate
(4i).
This compound was obtained as a yellow solid, mp 118-120°
(from 2-propanol); yield 82%; ir (nujol): 3334 (NH), 1751 (CO)
1
cm-1; H nmr (acetone-d6): ꢀ 3.03 (s, 3H, NMe), 3.76 (s, 3H,
OMe), 4.52 (s, 2H, NCH2), 7.22 – 7.77 (m, 5H, ArH), 8.11 (s,
1H, C2-H), 10.61 (br.s, 1H, NH).
Isolation Procedure for Compounds 5a,i,j, 7c,e,k, 13.
Anal. Calcd. for C14H15N5O4: C, 52.99; H, 4.76; N, 22.07.
Found: C, 53.08; H, 4.65; N, 22.03.
After the reaction had completed the precipitate that formed
was collected by filtration, washed with small amount of alcohol
and recrystallised to give compounds 5a,i,j, 7c,e,k, 13. Mp's,
spectral and analytical data of compounds 5a,i and 7e are given
in ref. [9].
Methyl N-Methyl-N-(5-nitro-6-{[3-(trifluoromethyl)phenyl]-
amino} pyrimidin-4-yl)glycinate (4j).
This compound was obtained as a yellow solid, mp 115-116°
(from 2-propanol); yield 77%; ir (nujol): 3299 (NH), 1743 (CO)
cm-1; 1H nmr (deuteriochloroform): ꢀ 3.01 (s, 3H, NMe), 3.80 (s,
3H, OMe), 4.41 (s, 2H, NCH2), 7.42 – 8.03 (m, 4H, ArH), 8.15
(s, 1H, C2-H), 10.02 (br.s, 1H, NH).
N4-Methyl-5-nitroso-N6-[3-(trifluoromethyl)phenyl]pyrimidine-
4,6-diamine (5j).
This compound was obtained as green needles, mp 151-152°
(from methanol); yield 85% (using sodium methoxide in
methanol); 72% (using sodium ethoxide in ethanol); 60% (using
sodium propoxide in propanol); ir (KBr): 3344, 3249 (NH) cm-1;
1H nmr (deuteriochloroform): ꢀ 3.12, 3.30 (2d, J = 5,1 Hz, 3H,
NHMe), 7.45-7.97 (m, 4H, ArH), 8.12, 11.38 (2q, J = 5.1Hz,
1H, NHMe), 8.31, 8.38 (2s, 1H, C2-H), 9.95, 13.38 (br.s., 1H,
NH); ms: m/z 297 (M+).
Anal. Calcd. for C15H14F3N5O4: C, 46.76; H, 3.66; N, 18.18.
Found: C, 46.65; H, 3.62; N, 18.20.
4,6-Bis[N-methyl-N-(2-methoxy-2-oxoethyl)amino]-5-nitro-
pyrimidine (4k).
This compound was obtained as a yellow solid, mp 90-92°
1
(from 2-propanol); yield 62%; ir (nujol): 1750 (CO) cm-1; H
Anal. Calcd. for C12H10F3N5O: C, 48.49; H, 3.39; N, 23.56.
Found: C, 48.67; H, 3.21; N, 23.59.
nmr (deuteriochloroform): ꢀ 3.20 (s, 6H, 2NMe), 3.79 (s, 6H,
2OMe), 4.34 (s, 4H, 2NCH2), 7.91 (s, 1H, C2-H).
Anal. Calcd. for C12H17N5O6: C, 44.04; H, 5.24; N, 21.40.
Found: C, 44.56; H, 5.34; N, 21.74.
9-Methyl-6-dimethylamino-7,9-dihydro-8H-purin-8-one (7c).
This compound was obtained as a colorless solid, mp 232-
234° (from 2-propanol); yield 80% (using sodium propoxide in
propanol); ir (KBr): 3175 (NH), 1710 (CO) cm-1; 1H nmr
(dimethylsulfoxide-d6): ꢀ 3.16 (s, 6H, N(Me)2), 3.30 (s, 3H,
NMe), 7.98 (s, 1H, C2-H), 10.73 (br.s., 1H, NH); 13C nmr
(dimethylsulfoxide-d6): ꢀ 25.1, 37.9, 103.9, 147.1, 148.4, 149.6,
152.8.
Methyl N-Methyl-N-{6-[methyl(phenyl)amino]-5-nitropyrimi-
din-4-yl}glycinate (4l).
This compound was obtained as a yellow solid, mp 104-105°
1
(from 2-propanol); yield 87%; ir (KBr): 1752 (CO) cm-1; H
nmr (acetone-d6): ꢀ 2.95 (s, 3H, NMe), 3.03 (s, 3H, NMe), 3.73
(s, 3H, OMe), 4.38 (s, 2H, NCH2), 7.22 – 7.40 (m, 5H, ArH),
8.18 (s, 1H, C2-H).
Anal. Calcd. for C8H11N5O: C, 49.73; H, 5.74; N, 36.25.
Found: C, 50.01; H, 5.68; N, 36.19.

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Vol 43
Crystal Data of Compound 7c.
Anal. Calcd. for C8H13N5O: C, 49.22; H, 6.71; N, 35.87.
Found: C, 49.17; H, 6.55; N, 36.00.
C8H12ClN5O, M = 229.671, monoclinic, space group P21/c, a
= 17.0490(3), b = 8.8346(7), c = 20.2167(7) Å, ꢀ = 94.657(2)°;
V = 3035.0(3) Å3, Z = 12, Dc = 1.508 g·cm–3, μ = 0.359 mm–1,
F(000) = 1440. Total number of reflection measured 20174,
unique 6643; 3967 observed reflections with I > 2ꢁ(I) were used
for refinement. Final R1 = 0.0968, wR2 = 0.2262.
X-ray diffraction data were collected on a Nonius Kappa
CCD diffractometer at the temperature 293 K using graphite-
monochromated MoKꢀ radiation (ꢂ = 0.71073 Å). Structure 7c
was solved by direct methods with SIR97 program [20] and
refined by full-matrix least squares techniques with anisotropic
non-hydrogen atoms. Hydrogen atoms were refined in the riding
model. The refinement calculations were carried out with the
help of SHELX97 program [21]. ORTEP [22] view of the
molecule is shown in Figure 2. Full crystallographic data for
structure 7c have been deposited at the Cambridge
Crystallographic Data Center (CCDC number 283166).
N4-Benzyl-N6-methyl-5-nitrosopyrimidine-4,6-diamine (5g).
This compound was obtained as a green solid, mp 130-132°
(from octane); yield 30% (using sodium methoxide in
methanol); 24% (using sodium ethoxide in ethanol); 20% (using
sodium propoxide in propanol); ir (KBr): 3287, 3333 (NH) cm-1;
1H nmr (deuteriochloroform): ꢁ 3.07, 3.25 (2d, J = 5.4 Hz, 3H,
NHMe), 4.76, 4.90 (2d, J = 6 Hz, 2H, NHCH2), 7.31-7.40 (m,
5H, ArH), 8.04, 8.26 (2br.s., 1H, NH), 8.25 (s, 1H, C2-H),
11.46, 11.75 (2 br.s., 1H, NH); 13C nmr (deuteriochloroform): ꢁ
26.0, 27.6, 43.2, 44.6, 127.3, 127.4, 128.4, 139.2, 136.1, 136.6,
145.7, 146.8, 162.8, 163.4, 164.8, 164.9.
Anal. Calcd. for C12H13N5O: C, 59.25; H, 5.39; N, 28.79.
Found: C, 59.45; H, 5.41; N, 28.56.
N4-Methyl-N6-(2-phenylethyl)-5-nitrosopyrimidine-4,6-diamine
(5h).
This compound was obtained as a green solid, mp 129-130°
(from hexane); yield 32% (using sodium methoxide in
methanol); ir (KBr): 3278, 3271 (NH) cm-1; 1H nmr
(dichloromethane-d2): ꢁ 2.95, 2.96 (2t, J = 6 Hz, PhCH2), 3.06,
3.24 (2d, J = 5.4 Hz, 3H, NHMe), 3.83, 3.99 (2d, J = 6 Hz, 2H,
NHCH2), 7.27-7.40 (m, 5H, ArH), 8.15, 8.20 (2br.s., 1H, NH),
8.20, 8.21 (2s, 1H, C2-H), 11.45, 11.53 (2 br.s., 1H, NH); 13C
nmr (dichloromethane-d2): ꢁ 26.5, 28.0, 35.5, 35.8, 41.4, 42.5,
126.8, 126.9, 128.8, 128.9, 129.01, 138.8, 138.9, 140.0, 146.6,
147.5, 163.6, 164.1, 165.2, 165.93.
Methyl N-Methyl-N-(9-methyl-8-oxo-8,9-dihydro-7H-purin-6-yl)-
glycinate (7k).
This compound was obtained as a colorless solid, mp 191-
192° (from 2-propanol); yield 64% (using sodium methoxide in
methanol); ir (KBr): 3161 (NH), 1730 (CO) cm-1; 1H nmr
(deuteriochloroform): ꢁ 3.43 (s, 6H, 2NMe), 3.76 (s, 3H, OMe),
4.41 (s, 2H, NCH2), 8.22 (s, 1H, C2-H), 10.49 (br.s., 1H, NH);
ms: m/z 251 (M+).
Anal. Calcd. for C10H13N5O3: C, 47.81; H, 5.22; N, 27.87.
Found: C, 48.00; H, 5.28; N, 27.78.
Anal. Calcd. for C13H15N5O: C, 60.69; H, 5.88; N, 27.22.
Found: C, 60.53; H, 5.83; N, 27.53.
Methyl 7-Methylaminothiazolo[5,4-d]pyrimidine-2-carboxylate (13).
5-Hydroxy-8-methyl-4-methylamino-5,8-dihydropteridine-6,7-
dione (6b).
This compound was obtained as a colorless needles, mp 231-
232° (from dimethylformamide); yield 78% (using sodium
methoxide in methanol); 40% (using sodium ethoxide in
ethanol); 35% (using sodium propoxide in propanol); ir (KBr):
This compound was obtained as a colorless solid, mp 218-
219° (dec) (from 2-propanol); yield 52% (using sodium
methoxide in methanol); ir (KBr): 3484 (OH), 3247 (NH), 1689
(CO) cm-1; 1H nmr (dimethylsulfoxide-d6): ꢁ 2.96 (s, 3H,
NHMe), 3.50 (s, 3H, NMe), 7.82 (br.s., 1H, NH), 8.24 (s, 1H,
C2-H); 13C nmr (dimethylsulfoxide-d6): ꢁ 28.4, 28.8, 106.0,
140.5, 150.2, 150.9, 151.7, 156.0.
1
3410 (NH), 1723 (CO) cm-1; H nmr (dimethylsulfoxide-d6): ꢁ
2.97 (d, J = 4.5 Hz, 3H, NHMe), 3.96 (s, 3H, OMe), 8.46 (s, 1H,
C2-H), 8.67 (q, J = 4.5 Hz, 1H, NH); 13C nmr (deuterio-
chloroform): ꢁ 27.7, 54.0, 132.3, 153.5, 157.1, 160.5, 163.5,
174.7; ms: m/z 224 (M+).
Anal. Calcd. for C8H8N4O2S: C, 42.85; H, 3.60; N, 24.99; S
14.3. Found: C, 42.88; H, 3.65; N, 25.02; S 14.00
Anal. Calcd. for C8H9N5O3: C, 43.05; H, 4.06; N, 31.38.
Found: C, 43.21; H, 4.02; N, 31.49.
Isolation Procedure for Compounds 5b,f-h, 6b,f-h.
5-Hydroxy-8-methyl-4-propylamino-5,8-dihydropteridine-6,7-
dione (6f).
After the reaction had completed the precipitate formed was
collected by filtratoin, dissolved in water and acidified with
concentrated hydrochloric acid to give compounds 6b,f-h. The
alcoholic mother liquor was concentrated under reduced
pressure to dryness, the solid obtained was recrystallised to give
compounds 5b,f-h. Mp, spectral and analytical data of
compound 5b are given in ref. [9].
This compound was obtained as a colorless solid, mp 110-
112° (dec) (from 2-propanol); yield 48% (using sodium
methoxide in methanol); ir (KBr): 3386 (OH), 3155 (NH), 1683
1
(CO) cm-1; H nmr (dimethylsulfoxide-d6): ꢁ 0.94 (t, J = 7 Hz,
3H, Me), 1.60 (m, J = 7 Hz, 2H, CH2), 3.43 (q, J = 7 Hz, 2H,
NHCH2), 3.49 (s, 3H, NMe), 7.82 (t, J = 7 Hz, 1H, NH), 8.21 (s,
1H, C2-H); 13C nmr (dimethylsulfoxide-d6): ꢁ 11.3, 21.9, 28.7,
42.4, 105.6, 140.7, 150.2, 150.6, 151.8, 155.9.
N4-Methyl-N6-propyl-5-nitrosopyrimidine-4,6-diamine (5f).
Anal. Calcd. for C10H13N5O3: C, 47.81; H, 5.22; N, 27.87.
Found: C, 47.60; H, 5.62; N, 27.56.
This compound was obtained as a green solid, mp 54-55°
(from hexane); yield 8% (using sodium methoxide in methanol);
ir (KBr): 3349 (NH) cm-1; 1H nmr (acetone-d6): ꢁ 0.97, 1.03 (2t,
J = 8Hz, 3H, Me), 1.67, 1.79 (2m, J = 8 Hz, 2H, CH2), 3.05,
3.23 (2d, J = 5 Hz, 3H, NHMe), 3.54, 3.72 (2q, J = 8 Hz, 2H,
NHCH2), 8.14 (s, 1H, C2-H), 8.89 (br.s., 1H, NH), 11.39, 11.59
(2 br.s., 1H, NH).
4-Benzylamino-5-hydroxy-8-methyl-5,8-dihydropteridine-6,7-
dione (6g).
This compound was obtained as a colorless solid, mp 181-
182° (dec) (2-propanol); yield 48% (using sodium methoxide in

Mar-Apr 2006
Methyl N-Methyl-N-(6-substituted-5-nitropyrimidin-4-yl)glycinates
275
methanol); 45% (using sodium ethoxide in ethanol); 30% (using
sodium propoxide in propanol); ir (KBr): 3379 (OH), 3204
(NH), 1687 (CO) cm-1; 1H nmr (dimethylsulfoxide-d6): ꢀ 3.44 (s,
3H, NMe), 4.63 (d, J = 5.7 Hz, 2H, NHCH2), 7.17 – 7.33 (m,
5H, ArH), 7.95 (t, J = 5.7 Hz, 1H, NH), 8.04 (s, 1H, C2-H); 13C
nmr (dimethylsulfoxide-d6): ꢀ 30.3, 47.4, 106.4, 127.0, 128.8,
129.7, 131.5, 141.9, 144.2, 144.6, 145.5, 156.7.
d6): ꢀ 1.42 (t, J = 7.2 Hz, 3H, Me), 3.38 (s, 6H, NMe2), 3.39 (s,
3H, NMe), 4.51 (q, J = 7.2 Hz, 2H, OCH2), 8.12 (s, 1H, C2-H).
Anal. Calcd. for C10H15N5O: C, 54.28; H, 6.83; N, 31.65.
Found: C, 54.09; H, 6.55; N, 31.75.
Isolation Procedure for Compounds 7d, 8d, 14d.
After the reaction had completed the precipitate formed was
collected by filtration, recrystallised to give sodium salt 8d,
which was dissolved in water. The resulting aqueous solution
was cooled to 0° and acidified with concentrated hydrochloric
acid to pH 3-4 to give compound 14d. Acidification of aqueous
solution at room temperature gave compound 7d, which was
collected by filtration and recrystallised.
Anal. Calcd. for C14H13N5O3: C, 56.18; H, 4.38; N, 23.40.
Found: C, 56.55; H, 4.22; N, 23.46.
5-Hydroxy-8-methyl-4-[(2-phenylethyl)amino]-5,8-dihydropteridine-
6,7-dione (6h).
This compound was obtained as a colorless solid, mp 142-
143° (dec) (from 2-propanol); yield 54% (using sodium
methoxide in methanol); ir (KBr): 3382 (OH), 3227 (NH), 1691
9-Methyl-6-pyrrolidino-7,9-dihydro-8H-purin-8-one (7d).
1
(CO) cm-1; H nmr (dimethylsulfoxide-d6): ꢀ 2.86 (t, J = 7.2 Hz,
Method A. This compound was obtained as a colorless solid,
mp > 250° (from 2-propanol); yield 33%; ir (KBr): 3159 (NH),
1700 (CO) cm-1; 1H nmr (deuteriochloroform): ꢀ 1.71 (t, J = 4.8
Hz, 4H, (CH2)2), 3.46 (s, 3H, NMe), 3.80 (t, J = 4.8 Hz, 4H,
N(CH2)2), 8.27 (s, 1H, C2-H), 10.70 (br.s., 1H, NH); 13C nmr
(dimethylsulfoxide-d6): ꢀ 24.7, 25.4, 46.9, 103.4, 145.3, 147.9,
150.5, 153.1.
CH2), 3.50 (s, 3H, NMe), 3.61 (q, J = 7.2 Hz, 2H, NHCH2), 7.15
– 7.28 (m, 5H, ArH), 8.00 (t, J = 7.2 Hz, 1H, NH), 8.08 (s, 1H,
C2-H); 13C nmr (dimethylsulfoxide-d6): ꢀ 28.0, 35.1, 41.8,
108.3, 126.0, 128.3, 128.6, 139.5, 141.6, 151.4, 151.5, 153.7,
156.0.
Anal. Calcd. for C15H15N5O3: C, 57.50; H, 4.83; N, 22.35.
Found: C, 57.55; H, 5.00; N, 22.44.
Anal. Calcd. for C10H13N5O: C, 54.78; H, 5.98; N, 31.94.
Found: C, 54.61; H, 5.78; N, 31.89.
Isolation Procedure for Compounds 7c, 8c, 9c, 10c.
Method B. A solution of compound 14d (0.1g, 0.38 mmol) in
anhydrous xylene (3 ml) was refluxed for 20 min. After cooling
to room temperature the precipitate was collected by filtration
and recrystallised to give 0.075 g (90%) of compound 7d, whose
properties are identical to those of the product obtained in
method A.
After the reaction had completed the precipitate formed was
collected by filtration, recrystallised to give sodium salt 8c,
which was dissolved in water. The resulting aqueous solution
was cooled to 0° and acidified with concentrated hydrochloric
acid to pH 3-4 to give compound 7c. The alcoholic mother
liquor was concentrated under reduced pressure to dryness, the
solid was purified using dry column vacuum chromatography
[14] (Merck silica gel 60 μm, eluent - toluene: ethylacetate 8:1)
to give compounds 9c or 10c.
9-Methyl-6-pyrrolidino-9H-purine-8-carboxylic Acid 7-Oxide,
Sodium Salt (8d).
This compound was obtained as a colorless solid, mp > 300°
(from methanol); yield 33% (using sodium methoxide in
Mp, spectral and analytical data of compound 7c are identical
to those of 7c isolated from the reaction of 4c with sodium
propoxide.
1
methanol); ir (KBr): 1690 (CO) cm-1; H nmr (dimethylsulfoxide-
d6): ꢀ 1.90 (m, 4H, (CH2)2), 3.35 (m, 4H, N(CH2)2), 3.50 (s, 3H,
NMe), 8.25 (s, 1H, C2-H).
6-Dimethylamino-9-methyl-9H-purine-8-carboxylic Acid 7-Oxide,
Sodium Salt (8c).
9-Methyl-6-pyrrolidino-9H-purine-8-carboxylic Acid 7-Oxide
(14d).
This compound was obtained as a colorless solid, mp > 300°
(from methanol); yield 25% (using sodium methoxide in
methanol), 27 % (using sodium ethoxide in ethanol) ir (KBr):
This compound was obtained as a colorless solid, mp 100-
101° (dec); yield 30% (using sodium methoxide in methanol); ir
(KBr): 3394 (OH), 3255 (NH), 1675 (CO) cm-1; due to its
unstability it was impossible to obtain reliable nmr spectra and
elemental analysis data.
1
1692 (CO) cm-1; H nmr (D2O): ꢀ 3.20 (s, 6H, NMe2), 3.61 (s,
3H, NMe), 7.87 (s, 1H, C2-H); 13C nmr (D2O): d 30.5, 41.1,
110.3, 136.4, 144.3, 153.0, 153.3, 159.5.
8-Methoxy-N,N,9-trimethyl-9H-purin-6-amine (9c).
Isolation Procedure for Compounds 7l, 9l, 10l.
This compound was obtained as a yellowish solid, mp 100-
100.5° (Rf = 0.51, 50% ethyl acetate in benzene (v/v)); yield
31% (using sodium methoxide in methanol); H nmr (acetone-
d6): ꢀ 3.44 (s, 6H, NMe2), 3.51 (s, 3H, NMe), 4.15 (s, 3H, OMe),
8.13 (s, 1H, C2-H); 13C nmr (acetone-d6): ꢀ 28.1, 39.1, 58.0,
117.5, 152.1, 152.6, 154.6, 155.7.
Anal. Calcd. for C9H13N5O: C, 52.16; H, 6.32; N, 33.79.
Found: C, 52.07; H, 6.15; N, 33.95.
After the reaction had completed the solution was
concentrated under reduced pressure. The residue was purified
by dry column vacuum chromatography [14] (Merck silica gel
40 μm, elution with 0-100% ethyl acetate in benzene (v/v) with
10% increment in ethyl acetate concentration for each fraction
collected) to give compounds 9l or 10l and 7l (order of elution).
Mp, spectral and elemental analysis data of compound 7l are
given in ref. [9].
1
8-Ethoxy-N,N,9-trimethyl-9H-purin-6-amine (10c).
8-Methoxy-N,9-dimethyl-N-phenyl-9H-purin-6-amine (9l).
This compound was obtained as a yellowish solid, mp 99-
100° (Rf = 0.70, 50% ethyl acetate in benzene (v/v)); yield 3%
(using sodium ethoxide in ethanol); H nmr (dimethylsulfoxide-
This compound was obtained as a yellow solid, mp 49-50° (Rf
= 0.42, 50% ethyl acetate in benzene (v/v)); yield 31% (using
sodium methoxide in methanol); H nmr (acetone-d6): ꢀ 3.52 (s,
1
1

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Vol 43
3H, NMe), 3.83 (s, 3H, NMe), 4.00 (s, 3H, OMe), 7.25 – 7.41
(m, 5H, ArH), 8.16 (s, 1H, C2-H); 13C nmr (acetone-d6): ꢀ 26.6,
39.2, 56.4, 116.9, 125.6, 126.8, 128.7, 146.5, 150.2, 151.9,
152.2, 154.8.
Anal. Calcd. for C14H15N5O: C, 62.44; H, 5.61; N, 26.01.
Found: C, 62.27; H, 5.46; N, 25.98.
6-Methoxy-N-methyl-5-nitrosopyrimidin-4-amine (12).
This compound was obtained as a blue solid, mp 151-152° (Rf
= 0.87, 50% ethyl acetate in benzene (v/v)); yield 5% (using
sodium methoxide in methanol); ir (KBr) 3299 (NH) cm-1; H
nmr (acetone-d6): ꢀ 3.10 (d, J = 5 Hz, 3H, NHMe), 4.28 (s, 3H,
OMe), 8.44 (s, 1H, C2-H), 11.00 (q, J = 5 Hz, 1H, NH).
Anal. Calcd. for C6H8N4O2: C, 42.86; H, 4.80; N, 33.32.
Found: C, 43.01; H, 4.85; N, 33.55.
1
8-Ethoxy-N,9-dimethyl-N-phenyl-9H-purin-6-amine (10l).
This compound was obtained as a yellow solid, mp 40-42° (Rf
= 0.48, 50% ethyl acetate in benzene (v/v)); yield 4% (using
Acknowledgements.
1
sodium ethoxide in ethanol); H nmr (acetone-d6): ꢀ 1.24 (t, J =
We are grateful to M. Kreneviciene and A. Karosiene for
recording nmr and ir spectra, to E. Kersuliene and M. Gavrilova
for the elemental analyses, and to Dr. S. Belyakov (Institute of
Organic Synthesis, Ryga, Latvia) for the X-ray measurements.
The work was supported by Lithuanian Science and Study
Foundation (Grant No. T-05292)
6 Hz, 3H, Me), 2.85 (s, 3H, NMe), 3.46 (s, 3H, NMe), 4.20 (q, J
= 6 Hz, 2H, OCH2), 7.12 – 7.44 (m, 5H, ArH), 8.13 (s, 1H,
C2-H).
Anal. Calcd. for C15H17N5O: C, 63.59; H, 6.05; N, 24.72.
Found: C, 63.48; H, 6.42; N, 24.70.
Isolation Procedure for Compounds 6m, 7m, 11m, 12.
REFERENCES AND NOTES
After the reaction had completed the precipitate that formed
was collected by filtration, dissolved in water and acidified with
concentrated hydrochloric acid to give compound 6m. The
mother liquor was concentrated under reduced pressure to
dryness, the residue was purified using dry column vacuum
chromatography [14] (Merck silica gel 40 μm, elution with 0-
100% ethyl acetate in benzene (v/v) with 2% increment in ethyl
acetate concentration for each fraction collected) to give
compounds 11m, 12 and 7m (order of elution).
[1] M. Otmar, M. Masojidkova and A. Holy, Tetrahedron, 53,
391 (1997).
[2] M. Otmar, M. Masojidkova, I. Votruba and A. Holy, Bioorg.
Med. Chem., 12, 3187 (2004)
[3] L. G. J. Hammarstrom, D. B. Smith, F. X. Talamas, S. D.
Labadie and N. E. Krauss, Tetrahedron Lett., 43, 8071 (2002).
[4] L. G. J. Hammarstrom, M. E. Meyer, D. B. Smith and F. X.
Talamas, Tetrahedron Lett., 44, 8361 (2003).
[5] F. Nohara, M. Nishii, K. Ogawa, K. Isono, M. Ubukata, T.
Fujii and T. Saito, Tetrahedron Lett., 28, 1287 (1987).
[6] K. Ogawa, M. Nishii, J. Inagaki, F. Nohara, T. Saito, T. Itaya
and T. Fujii, Chem. Pharm. Bull., 40, 343 (1992).
[7] K. Ogawa, T. Itaya and T. Fujii, Heterocycles, 38, 1225
(1994).
[8] T. Fujii, T. Itaya and K. Ogawa, Heterocycles, 44, 573
(1997).
[9] I. Susvilo, A. Brukstus and S. Tumkevicius, Tetrahedron
Lett., 46, 1841 (2005).
5-Hydroxy-8-methyl-4-phenylthio-5,8-dihydropteridine-
6,7-dione (6m).
This compound was obtained as a colorless solid, mp 220-
222° (dec) (from 2-propanol); yield 44% (using sodium
methoxide in methanol), 30% (using sodium propoxide in
propanol); ir (KBr): 3065 (OH), 1702 (CO) cm-1; 1H nmr
(dimethylsulfoxide-d6): ꢀ 3.51 (s, 3H, NMe), 7.49 (s, 5H, ArH),
8.38 (s, 1H, C2-H); 13C nmr (dimethylsulfoxide-d6): ꢀ 28.8,
118.7, 129.2, 129.3, 129.4, 135.8, 142.4, 150.4, 150.7, 153.6,
155.7.
[10] W. R. Boon, G. M. Jones and G. R. Ramage, J. Chem. Soc.,
96 (1951).
Anal. Calcd. for C13H10N4O3S: C, 51.65; H, 3.33; N, 18.53.
Found: C, 51.62; H, 3.30; N, 18.42.
[11] J. Clark, M. Curphey and I. W. Southon, J. Chem. Soc.,
Perkin Trans. I, 1611 (1974).
[12] F. L. Rose, J. Chem. Soc., 4116 (1954).
[13] R. K. Robins and H. H. Lin, J. Am. Chem. Soc., 79, 490
(1957).
[14] D. S. Pedersen and Ch. Rosenbohm, Synthesis, 2431 (2001).
[15] P. A. Collins Cafiero, C. S. French, M. D. McFarlane, R. K.
Mackie and D. M. Smith, J. Chem. Soc., Perkin Trans. I, 1375 (1997).
[16] P. A. Collins, M. D. McFarlane, R. K. Mackie and D. M.
Smith, Tetrahedron, 48, 7887 (1992).
9-Methyl-6-phenylthio-7,9-dihydro-8H-purin-8-one (7m).
This compound was obtained as a colorless solid, mp > 250°
(Rf = 0.38, 50% ethyl acetate in benzene (v/v)); yield < 1%; ir
(KBr): 1715 (CO) cm-1; 1H nmr (acetone-d6): ꢀ 3.39 (s, 3H,
NMe), 7.45 – 7.56 (m, 5H, ArH), 8.38 (s, 1H, C2-H), 10.37
(br.s., 1H, NH).
Anal. Calcd. for C12H10N4OS: C, 55.80; H, 3.90; N, 21.69.
Found: C, 55.60; H, 3.78; N, 21.79.
[17] M. D. McFarlane, D. M. Smith, G. Ferguson and B. Kaitner,
J. Chem. Soc., Perkin Trans. II, 893 (1989).
[18] P. N. Preston, D. M. Smith and G. Gettennant, eds,
Benzimidazoles and congeneric tricyclic compounds, Wiley
Interscience, NY, 1981, pp 313-316.
[19] R. Arshady, E. Atherton, D. L. Clive and R. C. Sheppard, J.
Chem. Soc., Perkin Trans. I, 529 (1981).
[20] A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C.
Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori and R.
Spagna, J. Appl. Crystallogr. 32, 115 (1999).
[21] G. M. Sheldrick, SHELXL97, Program for the Refinement of
Crystal Structures, University of Göttingen, Germany, (1997).
[22] C. K. Johnson, ORTEP-II, Report ORNL-5138. Oak Ridge
National Laboratory, Oak Ridge, TN, USA, (1976).
9-Methyl-6-phenylthio-9H-purine 7-Oxide (11m).
This compound was obtained as a yellow needles, mp 200-
201° ((Rf = 0.95, 50% ethyl acetate in benzene (v/v)); yield 3%
(using sodium methoxide in methanol); 1H nmr (dimethyl-
sulfoxide-d6): ꢀ 3.56 (s, 3H, NMe), 7.52 – 7.61 (m, 5H, ArH),
8.34 (s, 1H, C2-H), 8.70 (s, 1H, C8-H), 13C nmr (dimethyl-
sulfoxide-d6): ꢀ 27.2, 121.9, 126.7, 129.4, 129.8, 135.8, 150.8,
156.4, 156.6, 169.2
Anal. Calcd. for C12H10N4OS: C, 55.80; H, 3.90; N, 21.69.
Found: C, 55.55; H, 3.81; N, 21.47.