Side-chain transformations of 6- and 7-substituted 1,3-dimethyllumazines (=1,3-dimethylpteridine-2,4(1H,3H)-diones)

Article abstract of DOI:10.1002/hlca.200790118

A series of side chain reactions starting from the 6- and 7-styryl-substituted 1,3-dimethyllumazines 1 and 21 as well as from the 6- and 7-[2-(methoxycarbonyl)ethenyl]-substituted 1,3-dimethyllumazine 2 and 22 were performed first by addition of Br_2<

Full text of DOI:10.1002/hlca.200790118

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Helvetica Chimica Acta – Vol. 90 (2007)
Pteridines
Part CXVII1)
Side-Chain Transformations of 6- and 7-Substituted 1,3-Dimethyllumazines
(¼1,3-Dimethylpteridine-2,4(1H,3H)-diones)
by Kiyoshi Torigoe, Naohiro Kariya, Kazuyuki Soranaka, and Wolfgang Pfleiderer*
Fachbereich Chemie, Universität Konstanz, Postfach 5560, D-78457 Konstanz
A series of side chain reactions starting from the 6- and 7-styryl-substituted 1,3-dimethyllumazines 1
and 21 as well as from the 6- and 7-[2-(methoxycarbonyl)ethenyl]-substituted 1,3-dimethyllumazine 2
and 22 were performed first by addition of Br2 to the C¼C bond forming the 1’,2’-dibromo derivatives 3,
4, 24, and 26 in high yields (Schemes 1 and 3) (lumazine ¼ pteridine-2,4(1H,3H)-dione). Treatment of 3
with various nucleophiles gave rise to an unexpected tele-substitution in 7-position and elimination of the
Br-atoms generating 7-alkoxy- (see 5 and 6), 7-hydroxy- (see 7) and 7-amino-6-styryl-1,3-dimethyllu-
mazines (see 8 – 11) (Scheme 1). On the other hand, 4 underwent, with dilute DBU (1,8-diazabicy-
clo[5.4.0]undec-2-ene), a normal HBr elimination in the side chain leading to 18, whereas treatment with
MeONa afforded a more severe structural change to 19. Similarly, 24 and 26 reacted to 27, 32, and 33
under mild conditions, whereas in boiling NaOMe/MeOH, 24 gave 7-(2-dimethoxy-2-phenylethyl)-1,3-
dimethyllumazine (30) which was hydrolyzed to give 31 (Scheme 3). From the reactions of 4 and 24 with
DBU resulted the dark violet substance 20 and 25, respectively, in which DBU was added to the side
chain (Scheme 2). The styryl derivatives 1 and 21 could be converted, by a Sharpless dihydroxylation
reaction, into the corresponding stereoisomeric 6- and 7-(1,2-dihydroxy-2-phenylethyl)-1,3-dimethyllu-
mazines 34 – 37 (Scheme 4). The dihydroxy compounds 34 and 35 were also acetylated to 38 and 39
which, on catalytic reduction followed by formylation, yielded the diastereoisomer mixtures 40 and 41.
Deacetylation to 42 and 45 allowed the chromatographic separation of the diastereoisomers resulting in
the isolation of 43 and 44 as well as 46 and 47, respectively. Introduction of a 6- or 7-ethynyl side chains
proceeded well by a Sonogashira reaction with 6- (48) or 7-chloro-1,3-dimethyllumazine (55) yielding
49 – 51 and 56 – 58 (Scheme 5). The direction of H2O addition to the triple bond is depending on the
substituents since the 6- (49) and 7-(phenylethynyl)-1,3-dimethyllumazine (56) showed attack at the 2’-
position yielding 53 and 60, in contrast to the 6- (51) and 7-ethynyl-1,3-dimethyllumazine (58) favoring
attack at C(1’) and formation of 6- (52) and 7-acetyl-1,3-dimethyllumazine (59).
1. Introduction. – The synthesis of the pteridine molecular skeleton is mainly
achieved by two major approaches which starts either from a suitably substituted
pyrimidine derivative able to form on condensation the fused pyrazine ring or from an
appropriately substituted pyrazine derivative forming the pyrimidine ring on cycliza-
tion [2][3]. It is interesting to note that the most common modifications at the pteridine
molecular skeleton are dealing with nucleophilic displacement reactions of various
functional groups attached to the molecular skeleton, but very little chemistry has been
1
)
Part CXVI: [1].
ꢀ 2007 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 90 (2007)
1191
done in modifying side chains. Even since most naturally occurring pterins bear a C side
chain in 6-position, their introduction is usually achieved directly through the
condensation step during ring formation and not indirectly through subsequent chain
transformations (pterin ¼ 2-aminopteridin-4(1H)-one). In 1958, Tschesche and Glaser
[4] showed that the C(6) side chain in 6-acetonylisoxanthopterin (acetonyl ¼ 2-
oxopropyl) can be brominated and oxidized, respectively, to give the corresponding 1’-
hydroxy- and 1’-keto derivatives in reasonable yields. Goto and co-workers [5][6]
applied a similar approach in their urothion synthesis by converting the 6-[3’,4’-
bis(benzyloxy)-2’-oxobutyl] side chain into a fused thieno ring on treatment with P4S10.
Also Na2S2O4 treatment of d-erythro-neopterin [7] gave raise to a series of unexpected
6-substituted pterins indicating that the side chains bear a high potential for many
transformations. Some reactions have also been performed with biopterin to modify the
6-(1,2-dihydroxypropyl) side chain [8]. A rare case is also the addition reaction at the
side chain of 2,4-diamino-6-styrylpteridine 8-oxide leading to the corresponding 6-(1,2-
dihydroxy-2-phenylethyl) derivative of sofar unknown configuration [9]. Taylor and
co-workers [10– 12] undertook several efforts to build-up the complex side chain of
molybdopterin with only limited success. Recently, Suckling and co-workers [13][14]
performed various side chain reactions with 6-substituted pteridines which are
resembling our activities to some extent.
In this paper, we report about the reactivities of unsaturated side chains regarding
addition, elimination, and transformation reactions leading to a broad variety of new
lumazine derivatives (lumazine ¼ pteridine-2,4(1H,3H)-dione).
2. Results and Discussion. – As suitable starting materials for our investigations 6-
and 7-[(E)-styryl]-substituted 1,3-dimethyllumazines 1 and 21 as well as the 3-(1,3-
dimethyllumazin-6-yl)- and 3-(1,3-dimethyllumazin-7-yl)-substituted (2E)-prop-2-eno-
ic acid methyl esters 2 and 22 were considered which have been synthesized by an aldol-
type condensation and Wittig reactions [15]. Analogously, 7-acetyl-1,3-dimethylluma-
zine (59; see below) [16] reacted with triphenylphosphoranylidene)acetic acid methyl
ester to give the stereoisomers (2E)- and (2Z)-3-(1,3-dimethyllumazin-7-yl)but-2-enoic
acid methyl ester (23a and 23b, for formulas, see below) whose side chain structure was
assigned by the 1H-NMR chemical shifts of the MeC¼CHCOOMe moiety (downfield-
shifted signals in the (E)-isomer 23a as compared to the (Z)-isomer 23b, as predicted).
Bromine addition worked very well with 1 and 2 leading to the corresponding 6-
(erythro-1,2-dibromoethyl) derivatives 3 and 4 (Scheme 1). Anticipated elimination
reactions of 3 with various nucleophiles such as OHÀ ions, alkoxide ions, ammonia, and
primary and secondary amines proceeded, unexpectedly, by the formation of the 7-
substituted 1,3-dimethyl-6-styryllumazines 5 – 11. The most probable mechanism of
these interesting transformations involves the initial nucleophilic attack at C(7), as
exemplified by 12, leading to a tele-substitution of the Br-atom at C(1’) of the side chain
to give 13 which then tautomerizes to 14 and is followed by HBr elimination to give 5.
Treatment of 3 with dilute 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in dioxane
proceeded under HBr elimination giving rise to 6-[(1E)-2-bromo-2-phenylethenyl]-
1,3-dimethyllumazine (15), the structure of which was established by 2D-NMR (NOE
4
between Ho of Ph and HÀC(7), and J(HÀC(7), HÀC(1’)) observed). The assigned
configuration of 15 is in agreement with a trans-coplanar E2 mechanism. Treatment of 3

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Helvetica Chimica Acta – Vol. 90 (2007)
Scheme 1
with an excess of DBU at 508 was associated with the elimination of 2 mol of HBr
leading to the 1,3-dimethyl-6-(phenylethynyl)lumazine (49; see below) which can also
been obtained by a Sonogashira reaction between 6-chloro-1,3-dimethyllumazine (48;
see below) and phenylethyne, as already described in [17].
Another strange reaction was observed on treatment of 3 with sodium hydro-
gensulfide proceeding by formal reduction of both Br-atoms leading back to 1,3-
dimethyl-6-styryllumazine (1) (Scheme 1). We assume that the mechanism is again
initiated by a nucleophilic attack of the hydrogensulfide anion (HSÀ) at C(7) and
elimation of the Br-atom at C(1’) giving 16 as an intermediate which is then attacked at
the HSÀC(7) group with tele-substitution of the second Br-atom in the side chain.
Reaction of 3 with ethanethiol in the presence of DBU resulted in the formation of 6-
[2-(ethylthio)-2-phenylethyl)-1,3-dimethyllumazine (17) which followed most prob-
ably the preceeding mechanism to 1 with subsequent addition of ethanethiol.
Methylhydrazine was also able to convert 3 into 1.

Helvetica Chimica Acta – Vol. 90 (2007)
1193
Side-chain reactions with 2,3-dibromo-3-(1,3-dimethyllumazin-6-yl)propanoic acid
methyl ester (4) were more straightforward leading under mild treatment with diluted
DBU in dioxane to (2E)-2-bromo-3-(1,3-dimethyllumazin-6-yl)prop-2-enoic acid
methyl ester (18), and with MeONa to 2,2-dimethoxy-3-(1,3-dimethyllumazin-6-
yl)propanoic acid methyl ester 19 (Scheme 1). Treatment of either 4 or 18 with excess of
DBU resulted again in an unexpected reaction visualized by the appearance of a dark
violet solution from which purple crystals separated after several hours stirring at room
temperature. In these reactions, DBU was not only involved in the elimination process
but was also a reactant forming the complex molecule 20 (Scheme 2), the structure of
which was derived from its NMR and mass spectra as well as the elemental analysis. Its
long-wavelength UV/VIS spectrum is explained by the built-in merocyanine chromophor.
Scheme 2
Analogous investigations were performed starting from 1,3-dimethyl-7-[(E)-
styryl]lumazine (21) as well as from (2E)-3-(1,3-dimethyllumazin-7-yl)prop-2-enoic
acid methyl ester (22) [15] (Scheme 3). Bromination proceeded in high yields to 24 and
26. Heating of 24 to 908 in dioxane for 30min in the presence of DBU led again to a
violet precipitate 25, structurally related to 20 (Scheme 2). Reaction of 24 with NaOMe
in MeOH at room temperature led to 7-[(1E)-1-bromo-2-phenylethenyl]-1,3-dime-
thyllumazine (27), whereas heating under the same conditions gave 7-(2,2-dimethoxy-
2-phenylethyl)-1,3-dimethyllumazine (30), probably via the intermediates 28 and 29
(Scheme 3). Workup under acidic conditions was associated with hydrolysis of the
acetal function to the corresponding keto derivative which tautomerized right away to
the thermodynamically more stable vinylogous amide 31.

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Scheme 3
Mild treatment of 26 with NaOMe at room temperature resulted in the formation
of (2Z)-2-methoxy-3-(1,3-dimethyllumazin-7-yl)prop-2-enoic acid methyl ester (32),
and with triethylamine in MeOH, (2E)-3-bromo-3-(1,3-dimethyllumazin-7-yl)prop-2-
enoic acid methyl ester (33) was obtained (Scheme 3).
The styryllumazine derivatives 1 and 21 were also prone to a Sharpless
dihydroxylation reaction [18] applying the osmium-catalyzed asymmetric diol forma-
tion with AD-mix-a and AD-mix-b yielding 34 and 35 as well as 36 and 37, respectively,
according to Sharplessꢁs notation (Scheme 4). Acetylation of 34 and 35 led to the
diacetyl derivatives 38 and 39 which were catalytically reduced and formylated to give
the diastereoisomer mixtures of (6RS)-6-[(1S,2S)-bis(acetyloxy)-2-phenylethyl]-5-
formyl-5,6,7,8-tetrahydro-1,3-dimethyllumazine (40) and (6RS)-6-[(1R,2R-bis(acety-
loxy)-2-phenylethyl]-5-formyl-5,6,7,8-tetrahydro-1,3-dimethyllumazine (41). Deacety-
lation led to the diols 42 and 45 each of which could be separated into the two
corresponding pure diastereoisomers 43 and 44, and 46 and 47, respectively. The
absolute configurations of these isomers could not been assigned.
Another attractive approach for the introduction of C side chains in the lumazine
molecular skeleton is the very efficient Sonogashira reaction. The 6-chloro- (48) [19]
and 7-chloro-1,3-dimethyllumazine (55) [19] are valuable starting materials which react

Helvetica Chimica Acta – Vol. 90 (2007)
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Scheme 4
in the Pd-catalyzed reaction with phenylethyne and (trimethylsilyl)ethyne
(¼ethynyltrimethylsilane), respectively, in high yields to the corresponding 6- and 7-
substituted ethynyl derivatives 49 [17], 50 [20], 56, and 57 (Scheme 5), some of which
have recently also been described by two other groups. Desilylation of 50 and 57
proceeded well by fluoride treatment to give 6- (51) and 7-ethynyl-1,3-dimethylluma-
zine (58). Modification of the triple bond by Hg-catalyzed H2O addition was depending
on the nature of the side chain since the phenylethynyl derivatives showed nucleophilic
attack on the C(2’) atom to yield 53 and 60, respectively, whereas the ethynyl
derivatives 51 and 58 reacted at C(1’) to give 6-acetyl- (52) [21] and 7-acetyl-1,3-
dimethyllumazine (59) [21], respectively. The isomeric 6- and 7-(2-oxo-2-phenylethyl)
derivatives 53 and 60, respectively, exist, according to the 1H-NMR and UV spectra, as
!
tautomeric mixtures in which the equilibrium of 53 54 is in favor of the 6-(2-oxo-2-
phenylethyl) form 53, whereas 60 tautomerizes to the thermodynamically more stable
7,8-dihydro-1,3-dimethyl-7-(2-oxo-2-phenylethylidene)lumazine (31). Finally, 49 and
56 reacted smoothly with Br2 to form in high yield the 6- (61) and 7-[(1E)-1,2-dibromo-
2-phenylethenyl]-1,3-dimethyllumazine (62).

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Scheme 5
Experimental Part
General. TLC: precoated cellulose thin-layer sheets F 1440b LS 254 and silica gel thin-layer sheets F
1500 LS 254 from Schleicher & Schüll. Prep. TLC: silica gel 60 PF 254 from Merck. M.p.: Büchi
apparatus, model Dr. Tottoli; no corrections. The pKa measurements were performed by the
spectrophotometric method [16]. UV: Cary recording spectrometer, model 15; lmax (log e) in nm, sh ¼
shoulder. 1H-NMR: Bruker WM-250 spectrometer; d in ppm rel. to SiMe4, J in Hz. MS: in m/z.
1,3-Dimethyl-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (1) [15]. a) To a soln. of 6-(1,2-
dibromo-2-phenylethyl)-1,3-dimethylpteridine-2,4(1H,3H)-dione (3; 0.1 g, 0.22 mmol) in dioxane
(10ml) was added a soln. of NaSH (0.13 g) in H 2O (3 ml), and the mixture was stirred at r.t. for 24 h.
After evaporation, the residue was treated with H2O and the precipitate collected and dried in vacuo:
63 mg (97%) of 1. Pale yellow powder. M.p. 2388 ([15]: 237 – 2398).

Helvetica Chimica Acta – Vol. 90 (2007)
1197
b) To a soln. of 3 (0.1 g, 0.22 mmol) in dioxane (10 ml) was added methylhydrazine (1 ml) and H2O
(2.5 ml), and the mixture was stirred at r.t. for 17 h. After evaporation, H2O (5 ml) was added and the
precipitate collected, washed with a small amount of H2O, and dried in vacuo: 30mg (46%) of 1. Pale
yellow powder. M.p. 2398.
6-(1,2-Dibromo-2-phenylethyl)-1,3-dimethylpteridine-2,4(1H,3H)-dione (3). To a suspension of 1
(0.842 g, 2.86 mmol) in CHCl3 (20ml) was added 2 m Br2 in CHCl3 (2.5 ml, 5 mmol), and the mixture was
stirred at r.t. for 4 h. After evaporation, the residue was treated with MeOH and the precipitate collected
and dried in vacuo: 1.22 g (94%) of 3. Colorless powder. M.p. 1768. UV (MeOH): 245 (4.18), 260(sh,
4.10), 341 (3.83). 1H-NMR (CDCl3): 8.78 (s, HÀC(7)); 7.60– 7.50( m, 2 arom. H); 7.50– 7.40( m, 3 arom.
H); 5.88 (d, HÀC(1’)); 5.79 (d, HÀC(2’)); 3.76 (s, MeÀN(1)); 3.58 (s, MeÀN(3)). Anal. calc. for
C16H14Br2N4O2 (454.1): C 42.32, H 3.11, N 12.34; found: C 42.09, H 3.12, N 12.33.
2,3-Dibromo-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-6-yl)propanoic Acid Methyl Ester
(4). To a soln. of (2E)-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-6-yl)prop-2-enoic acid
methyl ester [15] (2; 0.7 g, 2.53 mmol) in CHCl3 (18 ml) was added a 2m Br2 in CHCl3 (1.5 ml, 3 mmol),
and the mixture was stirred at r.t. for 4 h. Then more Br2 soln. (0.5 ml, 1 mmol) was added and stirring
continued for additional 2 h. The mixture was evaporated, the residue treated with MeOH, and the
precipitate collected and dried in vacuo: 0.968 g (88%) of 4. Colorless powder. M.p. 163 – 1648. UV
(MeOH): 247 (4.16), 260(sh, 4.08), 339 (3.88). 1H-NMR (CDCl3): 8.67 (s, HÀC(7)); 5.62 (d, HÀC(1’));
5.33 (d, HÀC(2’)); 3.91 (s, MeO); 3.73 (s, MeÀN(1)); 3.55 (s, MeÀN(3)). Anal. calc. for C12H12Br2N4O4
(436.1): C 33.05, H 2.77, N 12.85; found: C 32.99, H 2.79, N 12.70.
7-Methoxy-1,3-dimethyl-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (5). To a suspension
of 3 (0.1 g, 0.22 mmol) in abs. MeOH (3 ml) was added DBU (0.1 ml, 0.67 mmol), and the mixture was
stirred for 1.5 h at r.t. The precipitate was collected, washed with MeOH, and dried in vacuo: 67 mg
(94%) of 5. Pale yellow powder. M.p. 271 – 2728. UV (MeOH): 232 (sh, 4.11), 306 (4.36), 375 (4.38).
1H-NMR ((D6)DMSO): 7.96 (d, J ¼ 16.2, 1 olef. H); 7.62 (m, 2 arom. H); 7.42 (d, J ¼ 16.2, 1 olef. H);
7.45 – 7.30( m, 3 arom. H); 4.18 (s, MeO); 3.69 (s, MeÀN(1)); 3.53 (s, MeÀN(3)). Anal. calc. for
C17H16N4O3 (324.3): C 62.96, H 4.97, N 17.28; found: C 62.65, H 4.99, N 17.51.
7-Ethoxy-1,3-dimethyl-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (6). To a suspension of
3 (0.1 g, 0.22 mmol) in abs. EtOH (3 ml) was added DBU (0.1 ml, 0.67 mmol) and stirred for 3 h at r.t.
The precipitate was collected, washed with EtOH, and dried in vacuo: 50mg (67%) of 6. Pale yellow
powder. M.p. 271 – 2728 (DMF). UV (MeOH): 232 (sh, 4.10), 307 (4.36), 376 (4.38). 1H-NMR
((D6)DMSO): 7.98 (d, J ¼ 16.1, 1 olef. H); 7.62 (m, 2 arom. H); 7.43 (d, J ¼ 16.1, 1 olef. H); 7.42 – 7.30( m, 3
arom. H); 4.61 (q, MeCH2O); 3.67 (s, MeÀN(1)); 3.53 (s, MeÀN(3)), 1.56 (t, MeCH2O). Anal. calc. for
C18H18N4O3 (338.4): C 63.89, H 5.36, N 16.56; found: C 63.98, H 5.44, N 16.57.
1,3-Dimethyl-7-hydroxy-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (7). a) Sodium salt
Na(7-H): To a suspension of 3 (0.1 g, 0.22 mmol) in EtOH (3 ml) was added 2.5n NaOH (0.5 ml,
1.3 mmol), and the mixture was stirred for 30min at r.t. The precipitate was collected and recrystallized
fron EtOH/H2O: 13 mg (17%) of Na(7-H). Pale orange crystals. M.p. > 3508. UV (MeOH): 222 (4.76),
264 (4.46), 303 (4.47), 383 (4.76), 412 (sh, 4.46). 1H-NMR ((D6)DMSO): 7.81 (d, J ¼ 16.2, 1 olef. H); 7.55
(m, 2 arom. H); 7.39 (d, J ¼ 16.2, 1 olef. H); 7.35 (m, 2 arom. H); 7.23 (m, 1 arom. H); 3.36 (s, MeÀN(1));
3.23 (s, MeÀN(3)). Anal. calc. for C16H13N4O3Na · H2O (350.3): C 54.86, H 4.31, N 15.99; found: C 54.93,
H 4.03, N 15.88.
b) OH Form 7: The crude sodium salt Na(7-H) was suspended in H2O (5 ml) and acidified with 1n
HCl to pH 1. The precipitate was collected and recrystallized from CHCl3/MeOH/hexane: 20mg (29%)
of 7. Yellow powder. M.p. 300 – 3068. 1H-NMR ((D6)DMSO): 7.69 (d, J ¼ 16.5, 1 olef. H); 7.67 (m, 2 arom.
H); 7.40( d, J ¼ 16.5, 1 olef. H); 7.44 – 7.29 (m, 3 arom. H); 3.49 (s, MeÀN(1)); 3.30( s, MeÀN(3)). Anal.
calc. for C16H14N4O3 (310.3): C 61.93, H 4.55, N 18.05; found: C 61.57, H 4.66, N 17.81.
7-Amino-1,3-dimethyl-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (8). To a soln. of
3
(0.1 g, 0.22 mmol) in dioxane (10 ml) was added conc. ammonia (10 ml), and the mixture was stirred at
r.t. for 15 h. The precipitate was collected, washed with H2O, and dried in vacuo: 19 mg (27%) of 8.
Bright yellow powder. M.p. 308 – 3108. UV (MeOH): 226 (4.53), 262 (4.17), 307 (4.30), 389 (4.41).
1H-NMR ((D6)DMSO): 7.83 (br. s, NH2); 7.73 (m, 2 arom. H); 7.57 (s, 2 olef. H); 7.44 – 7.37 (m, 2 arom.

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Helvetica Chimica Acta – Vol. 90 (2007)
H); 7.35 (m, 1 arom. H); 3.44 (s, MeÀN(1)); 3.27 (s, MeÀN(3)). Anal. calc. for C16H15N5O2 · 0.25 H2O
(313.8): C 61.24, H 4.98, N 22.32; found: C 61.26, H 4.83, N 21.82.
1,3-Dimethyl-7-(methylamino)-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (9). To a soln.
of 3 (0.1 g, 0.22 mmol) in dioxane (10 ml) was added 33% MeNH2/EtOH (5 ml), and the mixture was
stirred at r.t. for 20h. After concentration to 2 ml, the precipitate was collected, washed with H 2O, and
dried in vacuo: 9 mg (12%) of 9. Bright yellow powder. M.p. 2828. UV (MeOH): 234 (4.43), 264 (4.16),
310(4.26), 394 (4.34). 1H-NMR ((D6)DMSO): 7.56 (d, J ¼ 15.7, 1 olef. H); 7.40( m, 2 arom. H); 7.32 – 7.25
(m, 3 arom. H); 6.93 (d, J ¼ 15.7, 1 olef. H); 6.13 (br. q, MeNH); 3.55 (s, MeÀN(1)); 3.49 (s, MeÀN(3));
3.16 (d, MeNH). Anal. calc. for C17H17N5O2 · 0.25 H2O (327.9): C 62.28, H 5.38, N 21.36; found: C 62.31, H
5.25, N 21.06.
7-(Ethylamino)-1,3-dimethyl-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (10). To a soln.
of 3 (0.1 g, 0.22 mmol) in dioxane (10 ml) was added a 50% aq. EtNH2 soln. (5 ml), and the mixture was
stirred at r.t. for 20h. After concentration to 3 ml, H 2O (5 ml) was added and the precipitate collected
and recrystallized from CHCl3/hexane: 11 mg (15%) of 10. Bright yellow powder. M.p. 222 – 2248. UV
(MeOH): 235 (4.46), 264 (4.20), 311 (4.31), 395 (4.36). 1H-NMR ((D6)DMSO): 7.70( d, J ¼ 15.5, 1 olef.
H); 7.52 (m, 2 arom. H); 7.40– 7.30( m, 3 arom. H); 6.97 (d, J ¼ 15.5, 1 olef. H); 5.70(br. t, EtNH); 3.70–
3.58 (m, MeCH2N); 3.61 (s, MeÀN(1)); 3.50( s, MeÀN(3)); 1.37 (t, MeCH2N). Anal. calc. for
C18H19N5O2 · 0.25 H2O (341.9): C 63.24, H 5.75, N 20.48; found: C 63.47, H 5.74, N 20.22.
7-(Dimethylamino)-1,3-dimethyl-6-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione (11). To a
soln. of 3 (0.1 g, 0.22 mmol) in dioxane (10 ml) was added a 40% aq. Me2NH soln. (10ml), and the
mixture was stirred at r.t. for 19 h. After evaporation, the residue was treated with a small amount of H2O
and the precipitate collected and dried in vacuo: 30mg (40%) of 11. Bright yellow powder. M.p. 2118. UV
(MeOH): 240(4.55), 254 (sh, 4.52), 264 (sh, 4.51), 320(4.48), 397 (4.46). 1H-NMR (CDCl3): 7.67 (d, J ¼
16, 1 olef. H); 7.57 (m, 2 arom. H); 7.41 – 7.30( m, 3 arom. H); 7.16 (d, J ¼ 16, 1 olef. H); 3.64 (s,
MeÀN(1)); 3.51 (s, MeÀN(3)); 3.24 (s, Me2N). Anal. calc. for C18H19N5O2 (337.4): C 64.08, H 5.68, N
20.76; found: C 63.91, H 5.55, N 20.83.
6-[(1E)-2-Bromo-2-phenylethenyl]-1,3-dimethyl]pteridine-2,4(1H,3H)-dione (15). A soln. of
3
(0.22 g, 0.5 mmol) in dry dioxane (20 ml) was treated with DBU (0.4 g) by stirring at r.t. for 1 h. The
precipitate (DBU · HBr) was filtered off and the filtrate evaporated. The residue was separated by CC
(silica gel, AcOEt/hexane 1:2): less polar 15 (0.06 g, 30%; m.p. 143 – 1458) and more polar 49 (0.1 g, 68%;
m.p. 2278; see below). Data of 15: UV(MeOH): 203 (4.36), 244 (4.39), 296 (sh, 3.91), 357 (4.00).
1H-NMR (CDCl3): 8.33 (s, HÀC(7)); 7.55 (s, HÀC(1’)); 7.21 (m, 3 arom. H); 7.02 (m, 2 arom. H); 3.66 (s,
MeN(1)); 3.55 (s, MeÀN(3)). Anal. calc. for C16H13BrN4O2 (373.2): C 51.49, H 3.51, N 15.01; found: C
51.40, H 3.49, N 15.06.
6-[2-(Ethylthio)-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (17). To a suspension of 3
(0.1 g, 0.22 mmol) in ethanethiol (3 ml) was added DBU (0.1 ml, 0.67 mmol), and the mixture was stirred
at r.t. for 2 h. After evaporation, the residue was dissolved in CHCl3 (10ml), the soln. washed with H 2O
(5 ml), dried (Na2SO4), and concentrated, and the residue purified by CC (SiO2, toluene). The residue
of the product fractions was recrystallized from Et2O/MeOH/hexane: 64 mg (82%) of 17. Pale yellow
crystals. M.p. 114 – 1158. UV (MeOH): 239 (4.26), 337 (3.85). 1H-NMR (CDCl3): 8.25 (s, HÀC(7));
7.40– 7.20 ( m, 5 arom. H); 4.35 (t, HÀC(2’)); 3.66 (s, MeÀN(1)); 3.55 (s, MeÀN(3)); 3.47 (dd,
1 HÀC(1’)); 3.40( dd, 1 HÀC(1’)); 2.29 (q, MeCH2S); 1.08 (t, MeCH2S). Anal. calc. for C18H20N4O2S
(356.4): C 60.65, H 5.66, N 15.72; found: C 60.41, H 5.67, N 15.71.
(2E)-2-Bromo-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-6-yl)prop-2-enoic Acid Methyl
Ester (18). To a soln. of 4 (0.1 g, 0.23 mmol) in dioxane (20 ml) was added 0.67m DBU in dioxane
(0.92 ml, 0.62 mmol), and the mixture was stirred for 2 h at r.t. After dilution with AcOEt (150 ml), the
mixture was washed with H2O (3 Â 50ml), the org. phase dried (Na 2SO4) and concentrated, the residue
treated with MeOH, and the solid collected and dried in vacuo: 55 mg (68%) of 18. Pale orange powder.
M.p. 2048. UV(MeOH): (254 (4.08)), 285 (4.25), 360 (4.01). 1H-NMR (CDCl3): 8.55 (s, HÀC(7)); 7.26 (s,
1 olef. H); 4.02 (s, MeO); 3.70( s, MeÀN(1)); 3.52 (s, MeÀN(3)). Anal. calc. for C12H11BrN4O4 (355.1): C
40.58, H 3.12, N 15.78; found: C 40.85, H 3.26, N 15.49.
2,2-Dimethoxy-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-6-yl)propanoic Acid Methyl Es-
ter (19). In a soln. of Na (0.23 g, 10 mmol) in MeOH (10 ml), 4 (0.44 g, 1 mmol) was treated at r.t. for 2 h

Helvetica Chimica Acta – Vol. 90 (2007)
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with stirring. After neutralization with AcOH to pH 7 and evaporation, the residue was dissolved in H2O
(20ml) and extracted with CH 2Cl2 (2 Â 20ml), and the org. phase dried (Na 2SO4) and concentrated:
0.26 g (77%) of 19. Purification was achieved by prep. TLC (silica gel, 20 Â 20 Â 0.2 cm plate, Et2O). The
fastest moving band was eluted with CH2Cl2/MeOH 4 :1 (Rf 0.66) and the eluent evaporated: 98 mg
(29%) of pure 19. M.p. 1598. UV (MeOH): 203 (4.06), 238 (4.22), 333 (3.53). 1H-NMR (CDCl3): 8.99 (s,
HÀC(7)); 3.74 (s, COOMe); 3.54 (s, MeÀN(1)); 3.52 (s, MeÀN(3)); 3.82 (s, CH2); 3.23 (s, 2 MeO).
Anal. calc. for C14H18N4O6 (338.3): C 49.71, H 5.36, N 16.56; found: C 50.03, H 5.41, N 16.48.
4,5,6,7,8,9-Hexahydro-2-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-6-yl)-3H-2a,5a-diazaben-
zo[cd]azulene-1-carboxylic Acid Methyl Ester (20). To a soln. of 4 (0.105 g, 0.23 mmol) in abs. dioxane
(2 ml) was added DBU (0.1 ml, 0.67 mmol), and the mixture was stirred at r.t. for 2 h. After evaporation,
the residue was treated with MeOH and the precipitate collected, washed with MeOH, and dried in
vacuo: 33 mg (34%) of 20. Dark purple powder. M.p. 2238. UV (MeOH): 245 (4.31), 258 (sh, 4.20), 310
(sh, 4.16), 330(4.27), 373 (3.92), 415 (3.83), 473 (4.01), 496 (sh, 3.98), 536 (3.82). 1H-NMR (CDCl3):
6.58 (s, CH¼); 3.85 – 3.73 (m, 1 CH2); 3.70( s, MeO); 3.65 (s, MeÀN(1)); 3.60– 3.50( m, 1 CH2); 3.49 (s,
MeÀN(3)); 3.40( t, 1 CH2); 2.91 – 2.85 (m, 1 CH2); 2.40– 2.20 ( m, 1 CH2); 2.00 – 1.80 (m, 2 CH2). MS:
424. Anal. calc. for C21H24N6O4 · 0.5 H2O (433.5): C 58.18, H 5.81, N 19.39; found: C 58.43, H 5.71, N 19.18.
(2E)-3-(1,2,3,4-Tetrahydro-1,3-dimethyl-2,4-dioxopteridin-7-yl)prop-2-enoic Acid Methyl Ester (22)
1
[15]. H-NMR (CDCl3): 8.63 (s, HÀC(6)); 7.73 (d, J ¼ 12, HÀC(3’)); 7.15 (d, J ¼ 12, HÀC(2’)); 3.87 (s,
MeO); 3.74 (s, MeÀN(1)); 3.55 (s, MeÀN(3)). 1H-NMR ((D6)DMSO): 8.89 (s, HÀC(6)); 7.81 (d, J ¼ 12,
HÀC(3’)); 7.18 (d, J ¼ 12, HÀC(2’)); 3.79 (s, MeO); 3.57 (s, MeÀN(1)); 3.33 (s, MeÀN(3)).
(2E)-3-(1,2,3,4-Tetrahydro-1,3-dimethyl-2,4-dioxopteridin-7-yl)but-2-enoic Acid Methyl Ester (23a)
and (2Z)-3-(1,2,3,4-Tetrahydro-1,3-dimethyl-2,4-dioxopteridin-7-yl)but-2-enoic Acid Methyl Ester (23b).
To a soln. of 7-acetyl-1,3-dimethylpteridine-2,4-(1H,3H)-dione [21] (59; 1.17 g, 5 mmol) in dioxane
(50ml) was added (triphenylphosphoranylidene)acetic acid methyl ester (2.0g, 6 mmol), and the
mixture was stirred at r.t. for 3 days. After evaporation, and the residue was crystallized twice from
MeOH (60ml) to give 1.1 g (76%) of 23b as colorless needles. The combined filtrates were evaporated
and analyzed by TLC (AcOEt): two close spots. Separation of 150mg of crude material was achieved by
prep. TLC (silica gel, 20 Â 20cm plate, AcOEt). Elution of the faster moving band gave, after
evaporation, 50mg of 23a as a colorless crystal powder.
1
Data of 23a: M.p. 1948. UV (MeOH): 206 (4.26), 237 (4.14), 340 (3.95). H-NMR ((D6)DMSO):
9.00 (s, HÀC(6)); 7.00 (s, CHCO2Me); 3.75 (s, MeO); 3.57 (s, MeÀN(1)); 3.33 (s, MeÀN(3)); 2.59 (s,
MeC¼CH). 1H-NMR (CDCl3): 8.77 (s, HÀC(6)); 6.84 (s, CHCO2Me); 3.79 (s, MeO); 3.71 (s,
MeÀN(1)); 3.51 (s, MeÀN(3)); 2.64 (s, MeC¼CH). Anal. calc. for C13H14N4O4 (290.3): C 53.78, H 4.86,
N 19.30; found: C 53.98, H 4.87, N 19.12.
1
Data of 23b: M.p. 1858. UV (MeOH): 205 (4.38), 228 (4.39), 256 (sh, 4.15), 354 (4.12). H-NMR
((D6)DMSO): 8.58 (s, HÀC(6)); 6.38 (s, CHCO2Me); 3.54 (s, MeO); 3.50( s, MeÀN(1)); 3.32 (s,
MeÀN(3)); 2.27 (s, MeC¼CH). 1H-NMR (CDCl3): 8.48 (s, HÀC(6)); 6.19 (s, CHCO2Me); 3.69 (s,
MeO); 3.61 (s, MeÀN(1)); 3.54 (s, MeÀN(3)); 2.28 (s, MeC¼CH). Anal. calc. for C13H14N4O4 (290.3): C
53.78, H 4.86, N 19.30; found: C 53.68, H 4.82, N 18.90.
7-(1,2-Dibromo-2-phenylethyl)-1,3-dimethylpteridine-2,4(1H,3H)-dione (24). To a suspension of 1,3-
dimethyl-7-[(1E)-2-phenylethenyl]pteridine-2,4(1H,3H)-dione [15] (21; 0.6 g, 2.04 mmol) in CHCl3
(15 ml) was added 2m Br2 in CHCl3 (1.5 ml, 3 mmol), and the mixture was stirred at r.t. for 3 h. After
evaporation, the residue was treated with MeOH and the precipitate collected and dried in vacuo: 0.878 g
(95%) of 24. Colorless powder. M.p. 187 – 1888. UV (MeOH): 241 (4.25), 341 (4.06).1H-NMR (CDCl3):
8.68 (s, HÀC(6)); 7.60– 7.50 ( m, 2 arom. H); 7.50– 7.40 ( m, 3 arom. H); 5.75 (d, HÀC(1’)); 5.67 (d,
HÀC(2’)); 3.81 (s, MeÀN(1)); 3.57 (s, MeÀN(3)). Anal. calc. for C16H14Br2N4O2 (454.1): C 42.32, H 3.11,
N 12.34; found: C 42.11, H 3.12, N 12.41.
7-(4,5,6,7,8,9-Hexahydro-1-phenyl-3H-2a,5a-diazabenzo[cd]azulen-2-yl)-1,3-dimethylpteridine-
2,4(1H,3H)-dione (25). To a suspension of 24 (0.105 g, 0.23 mmol) in abs. dioxane (3 ml) was added
DBU (0.1 ml, 0.67 mmol), and the mixture was stirred at 908 for 30min. After evaporation, the residue
was treated with MeOH, the precipitate collected, washed with MeOH, and dried in vacuo: 24 mg (25%)
of 25. Dark green powder. M.p. 285 – 2878 (dec.). UV (MeOH): 237 (4.36), 321 (3.69), 370(3.56), 500
(4.48). 1H-NMR (CDCl3): 7.72 (s, CH¼); 7.45 – 7.30( m, 3 arom. H); 7.20– 7.10( m, 2 arom. H); 4.40( m,

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Helvetica Chimica Acta – Vol. 90 (2007)
1 CH2); 3.63 (s, MeÀN(1)); 3.47 (s, MeÀN(3)); 3.20– 3.10( m, 1 CH2); 2.40– 2.30( m, 1 CH2); 1.95 – 1.80
(m, 1 CH2); 1.65 – 1.50( m, 1 CH2). MS: 442. Anal. calc. for C25H26N6O2 (442.5): C 67.86, H 5.92, N 18.99;
found: C 67.40, H 5.89, N 18.85.
2,3-Dibromo-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-7-yl)propanoic Acid Methyl Ester
(26). To a suspension of 22 [15] (1.79 g, 6.5 mmol) in CHCl3 (70ml) was added Br 2 (0.7 ml, 14 mmol),
and the mixture was stirred at r.t. for 3 h. After evaporation, the residue was treated with MeOH and the
precipitate collected, washed with MeOH, dried (2.34 g), and purified by recrystallization from AcOEt/
hexane: 1.93 g (68%) of 26. Colorless crystals. M.p. 144 – 1458. UV (MeOH): 240(4.14), 343 (3.90).
1H-NMR (CDCl3): 8.56 (s, HÀC(6)); 5.58 (d, HÀC(2’)); 5.15 (d, HÀC(1’)); 3.94 (s, MeO); 3.74 (s,
MeÀN(1)); 3.56 (s, MeÀN(3)). Anal. calc. for C12H12Br2N4O4 (436.1): C 33.05, H 2.77, N 12.85; found: C
33.17, H 2.80, N 12.87.
7-[(1E)-1-Bromo-2-phenylethenyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (27). To a suspension 24
(0.1 g, 0.22 mmol) in abs. MeOH (2 ml) was added 2.2m MeONa in MeOH (0.5 ml, 1.1 mmol), and the
mixture was stirred at r.t. for 3 h. The precipitate was collected, washed with MeOH, and dried in vacuo:
58 mg (71%) of 27. Pale yellow powder. M.p. 245 – 2468 (from DMF). UV (MeOH): 243 (4.15), 372
(4.15). 1H-NMR (CDCl3): 9.11 (s, HÀC(6)); 8.34 (s, CH¼); 7.90– 7.80( m, 2 arom. H); 7.50– 7.40( m, 3
arom. H); 3.78 (s, MeÀN(1)); 3.57 (s, MeÀN(3)). Anal. calc. for C16H13BrN4O2 (373.2): C 51.49, H 3.51,
N 15.01; found: C 51.35, H 3.56, N 15.15.
7-(2,2-Dimethoxy-2-phenylethyl)-1,3-dimethylpteridine-2,4(1H,3H)-dione (30). To a suspension of
24 (0.1 g, 0.22 mmol) in abs. MeOH (2 ml) was added 2.2m MeONa in MeOH (0.5 ml, 1.1 mmol), and
then the mixture was refluxed for 30min. After cooling, the mixture was neutralized with dil. NH 4Cl soln.
and extracted with AcOEt, the extract washed with H2O, dried (Na2SO4), and concentrated. TLC
Analysis showed two substances 30 and 31 which were separated by prep. TLC (silica gel, AcOEt/acetone
7:3). The faster running band was eluted with CHCl3 and the eluent evaporated to give a syrup which
became crystalline on treatment with Et2O: 47 mg (60%) of 30. M.p. 134 – 1388. UV (MeOH): 202
(4.35), 236 (4.36), 335 (4.09), 348 (sh, 4.00). 1H-NMR (CDCl3): 8.90( s, HÀC(6)); 7.60– 7.40( m, 5 arom.
H); 3.70( s, MeÀN(1)); 3.66 (s, MeÀN(3)); 3.48 (s, CH2); 3.23 (s, 2 MeO). Anal. calc. for C18H20N4O4
(356.4): C 60.67, H 5.60, N 15.72; found: C 60.12, H 5.56, N 15.44.
7,8-Dihydro-1,3-dimethyl-7-(2-oxo-2-phenylethylidene)pteridine-2,4(1H,3H)-dione (31) and 1,3-Di-
methyl-7-(2-oxo-2-phenylethyl)pteridine-2,4(1H,3H)-dione (60). a) To a suspension of 24 (0.1 g,
0.22 mmol) in abs. MeOH (2 ml) was added 2.2m MeONa in MeOH (0.5 ml, 1.1 mmol), and the
mixture was refluxed for 30min. After cooling, the mixture was neutralized with dil. HCl soln. and then
concentrated to 1 ml, and the precipitate collected, washed with H2O, and dried in vacuo: 58 mg (85%) of
31. Yellow powder. M.p. 250– 251 8.
b) As described for 52, with 1,3-dimethyl-7-(phenylethynyl)pteridine-2,4(1H,3H)-dione (56; 0.292 g,
1 mmol), CF3COOH (15 ml), HgO (0.1 g), and H2O (1.5 ml). Purification by CC (SiO2, CHCl3/AcOEt
3 :1) gave 0.25 g (80%) of 31. Yellow powder. M.p. 250– 251 8. Recrystallization from MeOH gave yellow
1
needles. UV (MeOH): 203 (4.25), 237 (4.21), 313 (3.83), 411 (4.36), 428 (sh, 4.30). H-NMR (CDCl3):
13.65 (s, HÀN(8)); 8.38 (s, HÀC(6)); 7.91 – 7.48 (m, 5 arom. H); 6.35 (s, CHCOPh); 3.75 (s, MeÀN(1));
3.54 (s, MeÀN(3)). Anal. calc. for C16H14N4O3 (310.3): C 61.93, H 4.55, N 18.48; found: C 61.90, H 4.59, N
18.04.
(2Z)-2-Methoxy-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-7-yl)prop-2-enoic Acid Methyl
Ester (32). To a suspension of 26 (0.1 g 0.23 mmol) in abs. MeOH (4 ml) was added 2.2m MeONa (0.5 ml,
1.1 mmol), and the mixture was stirred at r.t. for 15 min. NH4Cl and H2O (10ml) were added. Then the
mixture was extracted with CHCl3 (2 Â 25 ml), the org. phase dried (Na2SO4), and concentrated, and the
resulting syrup crystallized from CHCl3/hexane: 20mg (28%) of 32. Colorless powder. M.p. 1928
1
(decomp.). UV (MeOH): 227 (4.22), 254 (sh, 3.92), 291 (sh, 3.68), 363 (4.31), 371 (sh, 4.30). H-NMR
(CDCl3): 8.37 (s, HÀC(6)); 5.92 (s, 1 olef. H); 3.90( s, MeOOC); 3.87 (s, MeOC¼CH); 3.61 (s,
MeÀN(1)); 3.52 (s, MeÀN(3)). MS: 306. Anal. calc. for C13H14N4O5 (306.3): C 50.98, H 4.61, N 18.29;
found: C 50.79, H 4.60, N 18.18.
(2E)-3-Bromo-3-(1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopteridin-7-yl)prop-2-enoic Acid Methyl
Ester (33). To a soln. of 26 (0.15 g, 0.34 mmol) in dioxane (8 ml) was added Et3N (0.1 ml, 0.72 mmol),
and the mixture was stirred for 8 h at r.t. After addition of AcOEt (25 ml), the org. phase was washed

Helvetica Chimica Acta – Vol. 90 (2007)
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with H2O (2 Â 15 ml), dried (Na2SO4), and concentrated, the residue treated with Et2O, and the solid
collected and dried in vacuo: 66 mg (55%) of 33. M.p. 141 – 1428. UV (MeOH): 206 (4.26), 226 (4.19),
353 (3.98). 1H-NMR (CDCl3): 8.61 (s, HÀC(6)); 6.86 (s, 1 olef. H); 3.69 (s, MeO); 3.65 (s, MeÀN(1));
3.56 (s, MeÀN(3)). Anal. calc. for C12H11BrN4O4 (355.2): C 40.58, H 3.12, N 15.78; found: C 40.78, H 3.17,
N 15.83.
6-[(1S,2S)-1,2-Dihydroxy-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (34). A mixture
of AD-mix-a (4.8 g) in H2O (18 ml), t-BuOH (36 ml) and methanesulfonamide (0.323 g, 3.4 mmol) was
cooled to 08, and then 1 (1.0g, 3.4 mmol) was added. The suspension was stirred at r.t. for 27 h, then
Na2SO3 (5.1 g) was added and the mixture stirred for another hour. The precipitate was collected, washed
with H2O, and then dried in a vacuum desiccator over P4O10 to give 0.89 g of a yellowish powder. The
reaction filtrate was extracted with CHCl3, the aq. layer again extracted with CHCl3 (2 Â 30ml), the
combined org. phase washed with 2n KOH, dried (Na2SO4), and concentrated, and the residue purified
by CC (SiO2, CHCl3, then CHCl3/MeOH 95 :5): 0.96 g (86%) of 34. Recrystallization from MeOH gave
yellowish crystals. TLC (CHCl3/MeOH 9 :1): Rf 0.47. M.p. 239 – 2408. [a]D ¼ þ40( c ¼ 0.8, DMF). UV
(MeOH): 204 (4.36), 240 (4.28), 249 (sh, 4.18), 336 (3.87), 347 (sh, 3.78). 1H-NMR ((D6)DMSO): 8.67 (s,
HÀC(7)); 7.36 – 7.20( m, 5 arom. H); 5.78 (d, J ¼ 5.8, OHÀC(1’)); 5.45 (d, J ¼ 5.1, OHÀC(2’)); 4.91 – 4.83
(m, HÀC(1’), HÀC(2’)); 3.53 (s, MeÀN(1)); 3.32 (s, MeÀN(3)). Anal. calc. for C16H16N4O4 (328.3): C
58.53, H 4.91, N 17.06; found: C 58.66, H 5.05, N 17.24.
6-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (35). As descri-
bed for 34, with AD-mix-b (4.8 g) and 1 (1.0g): 0.97 g (87%) of 35. Pale yellow crystals. TLC (CHCl3/
MeOH 9 :1). M.p. 240– 242 8. Rf 0.50. [a]D ¼ À38 (c ¼ 0.8, DMF). UV (MeOH): 205 (4.33), 240 (4.30),
250(sh, 4.15), 336 (3.88), 351 (sh, 3.72). 1H-NMR ((D6)DMSO): 8.65 (s, HÀC(7)); 7.35 – 7.19 (m, 5
arom. H); 5.76 (d, J ¼ 5.8, OHÀC(1’)); 5.43 (d, J ¼ 5.2, OHÀC(2’)); 4.90– 4.82 ( m, HÀC(1’), HÀC(2’));
3.52 (s, MeÀN(1)); 3.31 (s, MeÀN(3)). Anal. calc. for C16H16N4O4 (328.3): C 58.53, H 4.91, N 17.06;
found: C 57.84, H 4.95, N 16.83.
7-[(1S,2S)-1,2-Dihydroxy-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (36). To a mixture
of AD-mix-a (4.8 g) in H2O (18 ml) and t-BuOH (36 ml) was added methanesulfonamide (0.325 g,
3.4 mmol), followed by 21 (1.0g, 3.4 mmol). The suspension was stirred at r.t. for 24 h, then Na 2SO3
(5.1 g) was added and the mixture stirred for 2 h. After dilution with AcOEt (50ml), the aq. phase was
extracted with AcOEt (2 Â 25 ml), the combined org. phase dried (Na2SO4) and concentrated, and the
residue recrystallized from MeOH: 0.4 g (36%) of 36. Yellowish crystals. M.p. 1388 (shrinking), 145 –
1
1478. UV (MeOH): 204 (4.22), 237 (4.04), 333 (3.85). H-NMR ((D6)DMSO): 8.55 (s, HÀC(6)); 7.27
(m, 3 arom. H); 6.81 (m, 2 arom. H); 5.91 (d, OHÀC(1’)); 5.53 (d, OHÀC(2’)); 4.96 (m, HÀC(1’)); 4.80
(m, HÀC(2’)); 3.44 (s, MeÀN(1)); 3.30( s, MeÀN(3)). Anal. calc. for C16H16N4O4 (328.3): C 58.53, H
4.91, N 17.06; found: C 58.35, H 4.78, N 17.21.
7-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (37). As descri-
bed for 36, with AD-mix-b (4.8 g) and 21 (1.0g, 3.4 mmol): 0.65 g (58%) of 37. Yellowish crystals. M.p.
1
130– 135 8 (shrinking), 1458. UV (MeOH): 204 (4.21), 237 (4.05), 333 (3.87). H-NMR ((D6)DMSO):
8.56 (s, HÀC(6)); 7.27 (m, 5 arom. H); 5.91 (d, OHÀC(1’)); 5.53 (d, OHÀC(2’)); 4.93 (ꢂtꢁ, HÀC(1’)); 4.82
(ꢂtꢁ, HÀC(2’)); 3.46 (s, MeÀN(1)); 3.31 (s, MeÀN(3)). Anal. calc. for C16H16N4O4 · H2O (346.3): C 55.81,
H 5.27, N 16.27; found: C 56.06, H 5.10, N 16.08.
6-[(1S,2S)-1,2-Bis(acetyloxy)-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (38). To a sus-
pension of 34 (0.66 g, 2.0 mmol) in CH2Cl2 (15 ml) was added pyridine (1 ml) and then, after cooling with
ice, dropwise Ac2O (4 ml). The mixture was stirred at r.t. for 24 h, then evaporated to a yellowish syrup.
This residue was purified by CC (SiO2, AcOEt/hexane 1:1): 0.794 g (96%) of 38. Yellowish solid foam
which was recrystallized from AcOEt/hexane. Yellowish crystals. M.p. 131 – 1328. UV (MeOH): 242
(4.40), 256 (sh, 4.19), 332 (3.98). 1H-NMR (CDCl3): 8.46 (s, HÀC(7)); 7.37 – 7.27 (m, 5 arom. H); 6.39 (d,
HÀC(1’)); 6.29 (d, HÀC(2’)); 3.67 (s, MeÀN(1)); 3.54 (s, MeÀN(3)); 2.10( s, Ac); 2.08 (s, Ac). Anal.
calc. for C20H20N4O6 (412.4): C 58.25, H 4.89, N 13.59; found: C 58.18, H 4.91, N 13.61.
6-[(1R,2R)-1,2-Bis(acetyloxy)-2-phenylethyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (39). As de-
scribed for 38, with 35 (0.66 g, 2.0 mmol). CC gave 0.81 g (98%) of 39. Yellowish foam which was
recrystallized from AcOEt/hexane. Yellowish crystals. M.p. 131 – 1328. UV (MeOH): 242 (4.38), 256 (sh,
4.16), 332 (3.97). 1H-NMR (CDCl3): 8.45 (s, HÀC(7)); 7.37 – 7.27 (m, 5 arom. H); 6.39 (d, HÀC(1’)); 6.29

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Helvetica Chimica Acta – Vol. 90 (2007)
(d, HÀC(2’)); 3.67 (s, MeÀN(1)); 3.54 (s, MeÀN(3)); 2.10( s, Ac); 2.0 8 s(, Ac). Anal. calc. for
C20H20N4O6 (412.4): C 58.25, H 4.89, N 13.59; found: C 58.38, H 4.97, N 13.57.
(6RS)-6-[(1S,2S)-1,2-Bis(acetyloxy)-2-phenylethyl]-1,2,3,4,5,6,7,8-octahydro-1,3-dimethyl-2,4-dioxo-
pteridine-5-carboxaldehyde (40). A soln. of 38 (2.35 g, 5.3 mmol) in MeOH (30ml) was reduced under
H2 in the presence of PtO2 in a shaking apparatus. After 24 h, the catalyst was filtered off and the filtrate
evaporated to a syrup. Then a mixture of formic acid (20ml) and Ac 2O (20ml) was added and stirred for
2 h. After evaporation, the residue was purified by CC (SiO2, CHCl3, then CHCl3/MeOH 98 :2): 2.17 g
(92%) of 40. Yellowish solid. Recrystallization from AcOEt/hexane gave yellowish crystals. M.p. 1998.
1
UV (MeOH): 255 (sh, 2.99), 285 (4.20). H-NMR ((D6)DMSO): 8.53, 8.49 (2s, CHO); 7.60, 7.53 (2d,
HÀN(8)); 7.30– 7.10( m, 5 arom. H); 5.96, 5.56 (2d, HÀC(6)); 5.05 – 4.90 (m, HÀC(1’), HÀC(2’)); 3.50–
3.31 (m, CH2(7)); 3.34, 3.25 (2s, MeÀN(1)); 3.24 – 3.20( m, CH2(7)); 3.22, 3.11 (2s, MeÀN(3)); 2.20, 2.12
(2s, AcOÀC(1’)); 1.88, 1.68 (2s, AcOÀC(2’)). Anal. calc. for C21H24N4O7 · H2O (462.4): C 54.54, H 5.67, N
12.11; found: C 54.55, H 5.77, N 12.08.
(6RS)-6-[(1R,2R)-1,2-Bis(acetyloxy)-2-phenylethyl]-1,2,3,4,5,6,7,8-octahydro-1,3-dimethyl-2,4-dioxo-
pteridine-5-carboxaldehyde (41). As described for 40, with 39 (2.35 g, 5.3 mmol): 2.05 g (87%) of 41.
Yellowish solid. M.p. 1988. UV (MeOH): 205 (4.31), 252 (sh, 3.79), 284 (4.10). 1H-NMR ((D6)DMSO):
8.53, 8.49 (2s, CHO); 7.62, 7.53 (2d, HÀN(8)); 7.30– 7.11 ( m, 5 arom. H); 5.96, 5.56 (2d, HÀC(6)); 5.07 –
4.97 (m, HÀC(1’), HÀC(2’)); 3.50– 3.31 ( m, CH2(7)); 3.34, 3.25 (2s, MeÀN(1)); 3.24 – 3.18 (m, CH2(7));
3.22, 3.11 (2s, MeÀN(3)); 2.20, 2.12 (2s, AcOÀC(1’)); 1.88, 1.68 (2s, AcOÀC(2’)). Anal. calc. for
C21H24N4O7 · H2O (462.4): C 54.54, H 5.67, N 12.11; found: C 54.23, H 5.82, N 12.07.
(6RS)-6-[(1S,2S)-1,2-Dihydroxy-2-phenylethyl]-1,2,3,4,5,6,7,8-octahydro-1,3-dimethyl-2,4-dioxopter-
idine-5-carboxaldehyde (42). A soln. of 40 (0.2 g, 0.45 mmol) in abs. MeOH (30 ml) was treated with a
2.2m NaOMe in MeOH (0.5 ml) by stirring for 4 h. After neutralization by addition of Amberlite IR-120,
the mixture was filtered, the filtrate concentrated, and the residue purified by CC (SiO2, CHCl3/MeOH
98 :2, then CHCl3/MeOH 95 :5): 0.094 g (58%) of 42. Colorless solid which was recrystallized from
CHCl3/MeOH 95 :5. M.p. 145 – 1468 (dec.). UV (MeOH): 252 (sh, 3.94), 285 (4.17). 1H-NMR
((D6)DMSO): 8.60, 8.55 (s, CHO); 7.60, 7.50 (br. s, HÀN(8)); 7.36 – 7.10( m, 5 arom. H); 5.41, 5.25 (d,
OHÀC(1’)); 4.80, 4.73 (m, HÀC(6)); 4.70, 4.62 (d, HÀC(1’)); 4.45, 4.25 (d, OHÀC(2’)); 3.77, 3.70( dd,
1 HÀC(7)); 3.4 – 3.1 (m, 1 HÀC(7), HÀC(2’)); 3.31, 3.22 (s, MeÀN(1)); 3.14, 3.13 (s, MeÀN(3)). Anal.
calc. for C17H20N4O5 · H2O (378.4): C 53.96, H 5.86, N 14.81; found: C 54.22, H 5.79, N 14.85.
rel-(6S)-6-[(1S,2S)-1,2-Dihydroxy-2-phenylethyl]-1,2,3,4,5,6,7,8-octahydro-1,3-dimethyl-2,4-dioxo-
pteridine-5-carboxaldehyde (43) and rel-(6R)-6-[(1S,2S)-1,2-Dihydroxy-2-phenylethyl]-1,2,3,4,5,6,7,8-
octahydro-1,3-dimethyl-2,4-dioxopteridine-5-carboxaldehyde (44). The diastereoisomer mixture 42
(0.5 g) was separated by prep. TLC (silica gel, 0.1 g of 42 per 20 Â 20 Â 0.2 cm plate, developing twice
with AcOEt/MeOH 4 :1). The faster moving band was assigned to 43 and the slower moving band to 44.
Each band was extracted with CHCl3/MeOH, the extract concentrated, and the residue dried under high
vacuum.
Data of 43: Yield 0.18 g. M.p. 130 – 1358 (shrinking), 155 – 1608. Rf (AcOEt/MeOH 4 :1) 0.30. UV
(MeOH): 205 (4.29), 252 (sh, 3.75), 285 (4.09). 1H-NMR ((D6)DMSO): 8.52 (s, CHO); 7.61 (d,
HÀN(8)); 7.24 – 7.14 (m, 5 arom. H); 5.23 (d, OHÀC(1’)); 4.81 (dd, HÀC(6)); 4.71 (d, OHÀC(2’)); 4.48
(d, HÀC(1’)); 3.78 (dd, HÀC(2’)); 3.26 (s, MeÀN(1)); 3.21 (s, MeÀN(3)); 3.13 (m, CH2(7)). Anal. calc.
for C17H20N4O5 · 0.5 H2O (369.4): C 55.27, H 5.73, N 15.17; found: C 55.31, H 5.76, N 14.70.
Data of 44: Yield 0.15 g. M.p. 130 – 1358 (shrinking), 1858. Rf (AcOEt/MeOH 4 :1) 0.22. UV
(MeOH): 205 (4.31), 252 (sh, 3.80), 285 (4.09). 1H-NMR ((D6)DMSO): 8.61 (s, CHO); 7.49 (d,
HÀN(8)); 7.36 – 7.20( m, 5 arom. H); 5.41 (d, OHÀC(1’)); 4.74 (dd, HÀC(6)); 4.64 (dd, HÀC(1’)); 4.26
(d, OHÀC(2’)); 3.73 (dd, HÀC(2’)); 3.40( m, CH2(7)); 3.31 (s, MeÀN(1)); 3.15 (s, MeÀN(3)). Anal.
calc. for C17H20N4O5 · H2O (378.4): C 53.96, H 5.86, N 14.81; found: C 53.76, H 6.13, N 14.55.
(6RS)-6-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-1,2,3,4,5,6,7,8-octahydro-1,3-dimethyl-2,4-dioxo-
pteridine-5-carboxaldehyde (45). As described for 42, with 41: 0.1 g (58%) of 45. Colorless solid which
was recrystallized from CHCl3/MeOH 95 :5. M.p. 115 – 1358 (shrinking), 1508. UV (MeOH): UV
(MeOH): 205 (4.33), 252 (sh, 3.80), 284 (4.11). 1H-NMR ((D6)DMSO): 8.61, 8.52 (2s, CHO); 7.61, 7.50
(2d, HÀN(8)); 7.37 – 7.15 (m, 5 arom. H); 5.42, 5.21 (2d, OHÀC(1’)); 4.84 – 4.4.64 (m, HÀC(6),
OHÀC(2’)); 4.49, 4.26 (2d, HÀC(1’)); 3.81 – 3.68 (m, HÀC(2’)); 3.36, 3.31 (2s, MeÀN(1)); 3.26, 3.15 (2s,

Helvetica Chimica Acta – Vol. 90 (2007)
1203
MeÀN(3)); 3.35 – 3.15 (m, CH2(7)). Anal. calc. for C17H20N4O5 · H2O (378.4): C 53.96, H 5.86, N 14.81;
found: C 54.08, H 5.74, N 14.66.
rel-(6R)-6-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-1,2,3,4,5,6,7,8-octahydro-1,3-dimethyl-2,4-dioxo-
pteridine-5-carboxaldehyde (46) and rel-(6S)-6-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-1,2,3,4,5,6,7,8-
octahydro-1,3-dimethyl-2,4-dioxopteridine-5-carboxaldehyde (47). As described for 43/44, with the
diastereoisomer mixture 45 (0.5 g), assigning the faster moving band to 46 and the slower moving band to
47.
Data of 46: Yield 0.16 g. M.p. 115 – 1308 (shrinking), 1528. Rf (AcOEt/MeOH 4 :1) 0.30. UV
(MeOH): 205 (4.31), 252 (sh, 3.79), 284 (4.11). 1H-NMR ((D6)DMSO): 8.52 (s, CHO); 7.61 (d,
HÀN(8)); 7.27 – 7.15 (m, 5 arom. H); 5.21 (d, OHÀC(1’)); 4.83 (dd, HÀC(6)); 4.79 (d, OHÀC(2’)); 4.49
(d, HÀC(1’)); 3.78 (dd, HÀC(2’)); 3.36 (s, MeÀN(1)); 3.26 (s, MeÀN(3)); 3.25 – 3.15 (m, CH2(7)). Anal.
calc. for C17H20N4O5 · 0.5 H2O (369.4): C 55.27, H 5.73, N 15.17; found: C 55.16, H 5.64, N 14.53.
Data of 47: Yield 0.14 g. M.p. 130 – 1358 (shrinking), 1508. Rf (AcOEt/MeOH 4 :1) 0.22. UV
(MeOH): 205 (4.30), 252 (sh, 3.77), 284 (4.10). 1H-NMR ((D6)DMSO): 8.61 (s, CHO); 7.50( d,
HÀN(8)); 7.37 – 7.20( m, 5 arom. H); 5.41 (d, OHÀC(1’)); 4.74 (dd, HÀC(6)); 4.65 (d, HÀC(1’)); 4.26 (d,
OHÀC(2’)); 3.70( dd, HÀC(2’)); 3.40( m, CH2(7)); 3.36 (s, MeÀN(1)); 3.15 (s, MeÀN(3)). Anal. calc.
for C17H20N4O5 · H2O (378.4): C 53.96, H 5.86, N 14.81; found: C 53.81, H 6.24, N 14.54.
1,3-Dimethyl-6-(phenylethynyl)pteridine-2,4(1H,2H)-dione (49) [17]. a) To a soln. of 3 (0.1 g,
0.22 mmol) in dry dioxane (2 ml) was added DBU (0.1 ml, 0.67 mmol), and the mixture was stirred at 508
for 1 h. After evaporation, the residue was treated with MeOH and the precipitate collected, washed with
MeOH, and dried in vacuo: 36 mg (56%) of 49. Pale yellow powder. M.p. 2278 ([17]: 221 – 2238).
b) A mixture of 6-chloro-1,3-dimethylpteridine-2,4(1H,3H)-dione (48; 0.13 g, 0.57 mmol), CuI
(5 mg), [Pd(Ph3P)4] (10mg), and Et 3N (0.3 ml) in dioxane (5 ml) was treated with phenylethyne (0.1 ml,
0.95 mmol) at 1008 for 10min. After dilution with AcOEt (20ml), the mixture was extracted with H 2O
(3 Â 10ml), the org. phase dried (Na 2SO4) and concentrated, and the residue purified by CC (CHCl3):
0.107 g (64%) of crude 49. Recrystallization of the crystal powder from EtOH (25 ml)/H2O (1 ml) gave
0.079 g (47%) of 49. Yellowish crystals. M.p. 2278. UV (MeOH): 238 (sh, 4.02), 248 (sh, 4.10), 259 (sh,
4.13), 293 (4.45), 307 (sh, 4.41), 364 (4.16). 1H-NMR (CDCl3): 8.77 (s, HÀC(7)); 7.62 – 7.43 (m, 5 arom.
H); 3.74 (s, MeÀN(1)); 3.56 (s, MeÀN(3)). Anal. calc. for C16H12N4O2 (292.3): C 65.75, H 4.14, N 19.17;
found: C 65.95, H 4.27, N 18.98.
1,3-Dimethyl-6-[(trimethylsilyl)ethynyl]pteridine-2,4(1H,3H)-dione (50) [20]. To a mixture of 48
[19] (0.26 g, 1.14 mmol), CuI (10 mg), [Pd(Ph3P)4] (20mg), and Et 3N (0.6 ml) in dioxane (10 ml) was
added (trimethylsilyl)ethyne (0.25 ml, 1.7 mmol) and then heated to 1008 for 30min. After dilution with
AcOEt (40ml), the mixture was extracted with H 2O (3 Â 20ml), the org. layer dried (Na 2SO4) and
concentrated, and the residue purified by CC (SiO2, CHCl3): 0.3 g (96%) of crude 50. Recrystallization
from a small amount of EtOH (8 ml) yielded 0.25 g (76%) of 50. Colorless crystals. M.p. 129 – 1308 ([20]:
131 – 131.58). UV (MeOH): 260(sh, 4.24), 282 (4.34), 354 (4.05), 368 (sh, 3.93). 1H-NMR (CDCl3): 8.68
(s, HÀC(7)); 3.71 (s, MeÀN(1)); 3.54 (s, MeÀN(3)); 0.29 (s, Me3Si). Anal. calc. for C13H16N4O2Si
(288.4): C 54.14, H 5.59, N 19.43; found: C 54.08, H 5.60, N 19.45.
6-Ethynyl-1,3-dimethylpteridine-2,4(1H,3H)-dione (51). To a soln. of 50 (0.315 g, 1.09 mmol) in abs.
MeOH (25 ml) was added K2CO3 (0.165 g), and the mixture was stirred at r.t. for 1 h. After evaporation,
the residue was treated with sat. aq. NaHCO3 soln. and extracted with CHCl3 (3 Â 50ml). The org. layer
was dried (Na2SO4) and concentrated and the residue purified by CC (SiO2, CHCl3/AcOEt 3 :1): 0.134 g
(57%) of 51. Creamy powder. M.p. 236 – 2378 (dec.). UV (MeOH): 205 (4.09), 253 (4.21), 271 (4.19), 349
1
(3.95). H-NMR (CDCl3): 8.73 (s, HÀC(7)); 3.72 (s, MeÀN(1)); 3.55 (s, MeÀN(3)); 3.37 (s, CHꢀC).
Anal. calc. for C10H8N4O2 (216.2): C 55.56, H 3.73, N 25.91; found: C 55.41, H 3.79, N 25.41.
6-Acetyl-1,3-dimethylpteridine-2,4(1H,3H)-dione (52) [21]. A soln. of 51 (0.233 g, 1.08 mmol) in
CF3COOH (12 ml) was treated with HgO (76 mg) and H2O (1.2 ml) for 7 h at r.t. and subsequently for
30min at 40 8. After evaporation, some H2O was added, the mixture neutralized with dil. NH4OH soln.
and then extracted with CHCl3 (3 Â 20ml). The org. layer was dried (Na 2SO4) and concentrated and the
residue purified by CC (SiO2, CHCl3/AcOEt 3 :1): 0.188 g (74%) of 52. Pale yellow powder. M.p. 200 –
2028 ([20]: 203 – 2048). UV (MeOH): 248 (4.11), 281 (4.04), 332 (4.00). 1H-NMR (CDCl3): 9.29 (s,
HÀC(7)); 3.77 (s, MeÀN(1)); 3.57 (s, MeÀN(3)); 2.82 (s, Ac).

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Helvetica Chimica Acta – Vol. 90 (2007)
1,3-Dimethyl-6-(2-oxo-2-phenylethyl)pteridine-2,4(1H,3H)-dione (53). As described for 52, with 49
(0.2 g, 0.68 mmol), CF3COOH (10ml), HgO (65 mg), and H 2O (1 ml). Purification by CC (SiO2,
CHCl3/AcOEt 3 :1) gave 0.114 g (54%) of 53. Yellow powder. M.p. 1918. Recrystallization from AcOEt/
1
hexane gave yellow needles. UV (MeOH): 202 (4.32), 243 (4.30), 333 (3.89). H-NMR (CDCl3): 54:
13.47 (s, HN); 8.54 (s, HÀC(7)); 8.05 (m, 2 arom. H); 7.55 (m, 3 arom. H); 6.26 (s, CHCOPh); 3.74 (s,
MeÀN(1)); 3.55 (s, MeÀN(3)); 53: 8.68 (s, HÀC(7)); 8.05 (m, 2 arom. H); 7.55 (m, 3 arom. H); 4.74 (s,
CH2COPh); 3.74 (s, MeÀN(1)); 3.55 (s, MeÀN(3)). Anal. calc. for C16H14N4O3 (310.3): C 61.93, H 4.55,
N 18.06; found: C 61.96, H 4.59, N 17.55.
1,3-Dimethyl-7-(phenylethynyl)pteridine-2,4(1H,3H)-dione (56). A mixture of 7-chloro-1,3-dimeth-
ylpteridine-2,4(1H,3H)-dione [19] (55; 0.13 g, 0.57 mmol), CuI (5 mg), [Pd(Ph3P)4] (10mg), and Et 3N
(0.3 ml) in CHCl3 (5 ml) was treated with phenylethyne (0.1 ml, 0.95 mmol) at r.t. for 3 d with stirring.
After evaporation, the residue was purified by CC (CHCl3): 0.156 g (93%) of crude 56. Recrystallization
of the crystal powder from EtOH (65 ml)/H2O (9 ml) gave 0.099 g (59%) of 56. Yellow crystals. M.p.
275 – 2768. UV (MeOH): 237 (4.38), 242 (sh, 4.36), 264 (sh, 4.08), 305 (4.01), 365 (4.43), 372 (sh, 4.41).
1H-NMR (CDCl3): 8.68 (s, HÀC(6)); 7.74 – 7.36 (m, 5 arom. H); 3.74 (s, MeÀN(1)); 3.55 (s, MeÀN(3)).
Anal. calc. for C16H12N4O2 (292.3): C 65.75, H 4.14, N 19.17; found: C 65.48, H 4.18, N 18.92.
1,3-Dimethyl-7-[(trimethylsilyl)ethynyl]pteridine-2,4(1H,3H)-dione (57). To a mixture of 55 [19]
(0.5 g, 2.2 mmol), CuI (20 mg), [Pd(Ph3P)4] (40mg), and Et 3N (1.0ml) in dioxane (20ml) was added
(trimethylsilyl)ethyne (0.5 ml, 3.4 mmol) and then heated to 908 for 40min. After dilution with AcOEt
(40ml), the mixture was extracted with H 2O (3 Â 20ml), the org. layer dried (Na 2SO4) and
concentrated, and the residue purified by CC (SiO2, CHCl3): 0.57 g (90%) of crude 57. Recrystallization
from a small amount of EtOH yielded 0.42 g (66%) of 57. Yellowish crystals. M.p. 1658. UV (MeOH):
218 (4.19), 252 (4.18), 278 (sh, 3.82), 353 (4.11), 366 (sh, 4.04). 1H-NMR (CDCl3): 8.59 (s, HÀC(6)); 3.70
(s, MeÀN(1)); 3.54 (s, MeÀN(3)); 0.33 (s, Me3Si). Anal. calc. for C13H16N4O2Si (288.4): C 54.14, H 5.59,
N 19.43; found: C 53.84, H 5.41, N 19.42.
7-Ethynyl-1,3-dimethylpteridine-2,4(1H,3H)-dione (58). As described for 51, with 57 (0.235 g,
0.82 mmol), K2CO3 (0.125 g), and MeOH (20 ml): 0.095 g (54%) of 58. Pale yellowish powder. M.p.
258 – 2598 (dec.). UV (MeOH): 212 (4.24), 247 (4.25), 349 (4.05). 1H-NMR (CDCl3): 8.65 (s, HÀC(6));
3.71 (s, MeÀN(1)); 3.58 (s, CHꢀC); 3.55 (s, MeÀN(3)). Anal. calc. for C10H8N4O2 (216.2): C 55.56, H
3.73, N 25.91; found: C 55.35, H 3.87, N 25.56.
7-Acetyl-1,3-dimethylpteridine-2,4(1H,3H)-dione (59) [21]. As described for 52, with 58 (0.216 g,
1.0mmol), CF COOH (10ml), HgO (75 mg), and H 2O (1.2 ml): 0.117 g (50%) of 59. Colorless crystals.
3
M.p. 1758 ([21]: 1778). UV (MeOH): 248 (4.08), 348 (3.89). 1H-NMR (CDCl3): 9,17 (s, HÀC(6)); 3.79 (s,
MeÀN(1)); 3.58 (s, MeÀN(3)); 2.78 (s, Ac).
6-[(1E)-1,2-Dibromo-2-phenylethenyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (61). A soln. of 49
(0.584 g, 2 mmol) in CHCl3 (15 ml) was treated with 1m Br2 in CHCl3 (3 ml) by dropwise addition under
stirring. After 24 h the mixture was evaporated and the residue treated with Et2O to give 0.765 g (85%) of
crude material. Recrystallization from EtOH (200 ml) gave 0.49 g (54%) of 61. Yellowish crystals. M.p.
2268. UV (MeOH): 203 (4.27), 248 (4.11), 268 (sh, 3.99), 344 (3.81). 1H-NMR (CDCl3): 8.80( s,
HÀC(7)); 7.59 (m, 2 arom. H); 7.45 (m, 3 arom. H); 3.77 (s, MeÀN(1)); 3.57 (s, MeÀN(3)). Anal. calc.
for C16H12Br2N4O2 (452.1): C 42.51, H 2.68, N 12.39; found: C 42.72, H 2.71, N 12.34.
7-[(1E)-1,2-Dibromo-2-phenylethenyl]-1,3-dimethylpteridine-2,4(1H,3H)-dione (62). A soln. of 56
(0.37 g, 1.3 mmol) in CHCl3 (10ml) was heated to 40 8, and then Br2 in CHCl3 was dropwise added under
stirring till no decoloration took place. The mixture was stirred for another 30min and then concentrated
and the residue purified by CC (CHCl3) to give 0.55 g (96%) of crude 56. Recrystallization from EtOH
(100 ml) yielded 0.29 g (51%) of 56. Yellowish crystals. M.p. 217 – 2198. UV (MeOH): 238 (4.37), 354
(4.11). 1H-NMR (CDCl3): 8.85 (s, HÀC(6)); 7.58 – 7.45 (m, 5 arom. H); 3.77 (s, MeÀN(1)); 3.58 (s,
MeÀN(3)). Anal. calc. for C16H12Br2N4O2 (452.1): C 42.51, H 2.68, N 12.39; found: C 42.80, H 2.75, N
12.30.

Helvetica Chimica Acta – Vol. 90 (2007)
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REFERENCES
[1] R. Arendt, W. Pfleiderer, Pteridines 2005, 16, 184.
[2] D. J. Brown, ꢂFused Pyrimidines: Pteridinesꢁ, John Wiley & Sons, New York, 1988, Vol. 24; W.
Pfleiderer, ꢂPteridinesꢁ, in ꢂComprehensive Heterocyclic Chemistryꢁ, Eds. A. R. Katritzky, C. W.
Rees, Pergamon, Oxford, 1984, Vol. 5, Part 2B, p. 263 – 328.
[3] W. Pfleiderer, ꢂBicyclic 6-6 Systems: Pteridinesꢁ, in ꢂComprehensive Heterocyclic Chemistry IIꢁ, Eds.
A. R. Katritzky, C. W. Rees, E. F. Scriven, Pergamon, Oxford, 1996, Vol. 7, p. 679 – 736.
[4] R. Tschesche, A. Glaser, Chem. Ber. 1958, 91, 2081.
[5] A. Sakurai, M. Goto, J. Biochem. 1969, 65, 755.
[6] K. Sugiura, M. Goto, Bull. Chem. Soc. Jpn. 1973, 46, 939.
[7] B. Schircks, J. H. Bieri, M. Viscontini, Helv. Chim. Acta 1978, 61, 2731.
[8] M. Kappel, R. Mengel, W. Pfleiderer, Liebigs Ann. Chem. 1984, 1815.
[9] E. C. Taylor, K. L. Perlman, Y. Kim, I. P. Sword, P. A. Jacobi, J. Am. Chem. Soc. 1973, 95, 6413.
[10] E. C. Taylor, P. S. Ray, I. S. Darwish, J. L. Johnson, K. V. Rajagopalan, J. Am. Chem. Soc. 1989, 111,
7664.
[11] E. C. Taylor, R. Dçtzer, J. Org. Chem. 1991, 56, 1816.
[12] E. C. Taylor, S. Goswami, Tetrahedron Lett. 1991, 32, 7357.
[13] C. L. Gibson, A. Lang, K. Ohta, C. J. Suckling, J. Chem. Soc., Perkin Trans. 1 1999, 163.
[14] D. Guiney, C. L. Gibson, C. J. Suckling, Org. Biomol. Chem. 2003, 1, 664.
[15] S. Muranishi, R. Soyka, W. Pfleiderer, Pteridines 2004, 15, 10 .
[16] A. Albert, E. P. Serjeant, ꢂThe Determination of Ionization Constantsꢁ, Chapman and Hall, London,
1971.
[17] A. V. Gulevskaya, D. V. Shee, A. F. Pozharskii, Russ. Chem. Bull. 2003, 52, 1403.
[18] K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. Hartung, K. S. Jeong, H. L. Kwong, K.
Morikawa, Z. M. Wang, D. Xu, X. L. Zhang, J. Org. Chem. 1992, 57, 2768.
[19] H. Steppan, J. Hammer, R. Baur, R. Gottlieb, W. Pfleiderer, Liebigs Ann. Chem. 1982, 2135.
[20] N. Sato, S. Fukuya, J. Chem. Soc., Perkin Trans. 1 2000, 89.
[21] R. Baur, E. Kleiner, W. Pfleiderer, Liebigs Ann. Chem. 1984, 1798.
Received February 7, 2007