Preparation of 6-ethynylpteridine derivatives by Sonogashira coupling

Article abstract of DOI:10.3987/COM-12-12610

Sonogashira coupling of 6-sulfonyloxypteridine with various acetylenes is reported. Hydrolysis of the protecting groups with 1M NH₃ gave the 6-subustituted 2,4-diaminopteridine while hydrolysis with 1M NaOH gave the 6-subsituted pterin.

Full text of DOI:10.3987/COM-12-12610

HETEROCYCLES, Vol. 87, No. 1, 2013
79
HETEROCYCLES, Vol. 87, No. 1, 2013, pp. 79 - 89. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 26th October, 2012, Accepted, 14th November, 2012, Published online, 28th November, 2012
DOI: 10.3987/COM-12-12610
PREPARATION OF 6-ETHYNYLPTERIDINE DERIVATIVES BY
SONOGASHIRA COUPLING
Winston Nxumaloa,* and Andrew Dinsmoreb
a Department of Chemistry, University of Limpopo Turfloop campus, Limpopo,
Private Bag x1106, Sovenga 0727, South Africa
b School of Chemistry, University of the Witwatersrand, Johannesburg, Private bag
x3, P.O. Wits, 2050, South Africa
Abstract – Sonogashira coupling of 6-sulfonyloxypteridine with various
acetylenes is reported. Hydrolysis of the protecting groups with 1M NH3 gave the
6-subustituted 2,4-diaminopteridine while hydrolysis with 1M NaOH gave the
6-subsituted pterin.
INTRODUCTION
Pterins are incorporated into a number of redox active cofactors which are essential to all forms of life,
examples include tetrahydrobiopterin (BH4), the molybdenum cofactors (Moco), flavin and folic acid
(Figure 1). Deficiency in these essential cofactors results in severe birth defects and in most cases death.
The first total synthesis of pterins was reported in the 1940s and since then a number of natural occurring
pterins and their derivatives have been synthesized.1,2 However, most of the synthesized pterins are folic
acid derivatives and few synthetic routes in making non-folic acid derivatives exist.
Figure 1

80
HETEROCYCLES, Vol. 87, No. 1, 2013
The current methods of preparing non-folic acid derivatives include the oxidation of pterin with
trifluoroacetic acid/hydrogen peroxide (TFA/H2O2) and treatment of the resultant 8-oxide with
trifluoroacetic acid/acetyl chloride (TFA/AcCl) to give 6-chloropterin in an unusual Katada
rearrangement (Scheme 1).3 The chloride is displaced by thiols via nucleophilic substitution reactions and
acetylenes under Sonogashira coupling conditions, giving 6-substituted pterins. Other methods include
the condensation of pyrimidone or pyrimidine ring with a substituted glyoxal, α-carbonylmethylene group
and α-haloketones to give the corresponding 6-substituted pterin and pteridine rings, respectively
(Scheme 2).4-6 A number of natural pterin compounds have been synthesised following these procedures,
however, a number of problems such as selectivity of 6- vs 7-position and difficulty with certain chemical
transformations, have been reported.
Scheme 1
Scheme 2

HETEROCYCLES, Vol. 87, No. 1, 2013
81
The challenge now lies in developing a synthetic method which is selective and versatile. Work reported
by Joule et al.7 demonstrated the preparation of 6-tosyloxypteridine, selectively, in three steps starting
from tetraaminopyrimidine and glyoxilic acid. The 6-tosyloxypteridine was subsequently shown to
undergo Stille coupling reaction (Scheme 3).
Scheme 3
In this paper we report Sonogashira coupling reactions on 6-benzenesulfonyloxypteridine and selective
hydrolysis of the protecting groups to give exclusively the 6-substituted 2,4-diaminopteridines and
6-substituted pterins.
RESULTS AND DISCUSSION
Treating 2,4,5,6-tetraaminopyrimidine and glyoxylic acid in 2M H2SO4 gave 2,4-diaminopteridin-6-one 1
in 74% yield as described by Pfleiderer et al.8 The addition of Bredereck’s reagent9 afforded the more
soluble 2,4-bis(N,N-dimethylaminomethyleneamino)pteridin-6-one7 2 in 91% yield which was treated
with benzenesulfonyl chloride to give 2,4-bis(N,N-dimethylaminomethyleneamino)-6-benzene-
sulfonyloxypteridine 3 in 75% yield. With the protected 6-sulfonyloxypteridine 3 in hand, we were in a
position to attempt the Sonogashira coupling reactions. Subjecting 3 and phenylacetylene under
Sonogashira coupling conditions, after two hours, gave a mixture of two close running new products
which were characterised to be the desired Sonogashira product, 2,4-bis(N,N-dimethylaminomethylene-
amino)-6-(phenylethynyl)pteridine 4 along with the mono-deprotected product, 4-amino-2-(N,N-
dimethylaminomethyleneamino)-6-(phenylethynyl)pteridine 5 in a ratio of ~1:1 (Scheme 4). Work by
Joule et al.7 also reported the product mixture of desired Stille coupling product and mono-deprotected
product. Further purification of the two close running products, by flash chromatography, gave a product
distribution that favoured the mono-deprotected product 5 in ~1:9 ratio.

82
HETEROCYCLES, Vol. 87, No. 1, 2013
Scheme 4
By monitoring the reaction with HPLC-UV-APCI-MS, we discovered that the desired product 4 was the
only product when the reaction was quenched and the mono-deprotected 5 only formed after purification.
We postulated that the deprotection step was facilitated by the solvent system employed (5-10%
MeOH/DCM). Dissolving the 6-sulfonyloxypteridine 3 in DCM did not show any deprotection upon
standing for 24 hours, however, by dissolving 3 in methanol we observed two peaks at RT 8.43 and 8.87
min corresponding to the mono-deprotected and fully-deprotected 6-sulfonyloxypteridine, respectively
(Figure 2). It was therefore concluded that methanol is responsible for the mono-deprotection of the
Sonogashira product 4. We were unable to develop a methanol-free solvent system to purify our products
and the product mixture was carried into the next reaction without further purification.
Win254SM_100201114659
RT: 0.00 - 9.99
2/1/2010 11:46:59 AM
NL:
8.41
8.43
100
1.75E6
TIC MS
Win254SM
_10020111
4659
90
Relative Abundance
80
NH2
N
NH2
N
N
N
OSO2Ph
OSO2Ph
70
60
50
40
30
20
10
N
N
8.87
N
N
H2N
N
N
9.98
9.82
9.62
8.25
7.97
7.30
6.63
6
5.86
0.03
0.67
1.97
2.53
2.91
4.02
4.92
0
0
1
2
3
4
5
7
8
9
Time (min)
Win254SM_100201114659
T: ITMS + c APCI corona Full ms [100.00-600.00]
#
672-713
RT:
8.40-8.86
AV:
42
NL:
2.36E5
374.1
6
22000
0
20000
0
18000
0
16000
Intensit
0
y
14000
0
12000
0
10000
0
319.1
1
8000
0
6000
375.1
5
0
4000
0
376.1
2000
320.1
347.1
3
6
377.1
6
0
340.2
1
322.1
5
383.3
6
313.2
5
330.2
351.2
4
361.2
369.2
6
0
9
9
3
32
33
34
35
36
37
38
0
0
0
0
m/
0
0
0
z
Figure 2

HETEROCYCLES, Vol. 87, No. 1, 2013
83
Having shown that 6-sulfonyloxypteridine 3 can undergo Sonogashira coupling reactions, we investigated
varying the acetylenes. Treating 3 with ethynyltrimethylsilane under the Sonogashira coupling conditions
gave a mixture of two products which we assigned to be the desired coupling product 6 along with the
mono-deprotected product 7 in ~1:1 ratio (Figure 3). Further purification gave a product distribution in
favour of 7 in ~1:9 ratios.
N
NH2
SiMe3
N
SiMe3
N
N
N
N
N
+
N
N
N
N
N
N
N
6
7
Figure 3
When treating 6-sulfonyloxypteridine 3 with propargyl alcohol no desired product was observed, instead
we obtained the mono-deprotected starting material. Having discovered that methanol is responsible for
deprotection, we methylated the propargyl alcohol and proceeded with the Sonogashira coupling and
obtained the desired product 8 along with the mono-deprotected product 9 in 9:1 ratio in favour of 8
(Scheme 5).
Scheme 5
We intended that, under appropriate conditions, hydrolysis could be tuned to give initially the
2,4-diaminopteridine and under stronger hydrolytic conditions the corresponding pterin could be obtained.
Treating 6-ethynylpteridine 5 with 1M NH3 solution, under gentle reflux, gave the desired
2,4-diamino-6-(phenylethynyl)pteridine10 10 in 77% yield. Similarly 6-ethynylpteridine 7, and
6-(methoxypropynyl)pteridine 8, gave the corresponding 2,4-diamino-6-ethynylpteridine 11 in 76% yield
and 2,4-diamino-6-(3-methoxypropynyl)pteridine 12 in 74% yield, respectively (Scheme 6).10

84
HETEROCYCLES, Vol. 87, No. 1, 2013
Scheme 6
Treating 6-(phenylethynyl)pteridine 5 with 1M NaOH/ethanol solution under gentle reflux afforded the
desired 6-(phenylethynyl)pterin10 13 in 73% yield (Scheme 6). However, when using the same conditions
on the TMS-ethynylpteridine 7, and the 6-(methoxypropynyl)pteridine 9, the corresponding pterins were
not obtained.
We then turned our attention into monitoring the unsuccessful hydrolysis of TMS-pteridine 7, using
HPLC-MS over 12 hours. The first step in the reaction involves the removal of both the protecting groups
and the TMS group to give 2,4-diamino-6-ethynylpteridine 11, within the first hour. Formation of the
desired 6-ethynylpterin 14 is observed after two hours, however substantial amounts of 11 is still present.
Nucleophillic addition of an ethoxide group, presumably at the triple bond of 11 and 14, is observed after
3 hours with an addition of a second ethoxide group observed after 4 hours. The resulting pterin-ketals
undergo an unusual C-C bond cleavage reaction to give 6-methylpterin 15 (Scheme 7). When substituting
ethanol with methanol, similar nucleophillic additions of two methoxide groups were observed, as judged
by HPLC-MS where a 15 amu difference was observed.
N
TMS
N
NH2
N
O
N
N
N
N
N
N
N
HN
H2N
N
N
6+7
H2N
N
N
11
m/z 187
14
m/z 188
N
NH2
O
O
N
N
O
N
HN
H2N
H2N
N
N
N
N
m/z 234
m/z 233
O
N
NH2
N
O
O
N
N
HN
H2N
N
O
O
N
H2N
N
m/z279
m/z 278
O
N
N
N
HN
H2N
m/z 178
15
Scheme 7

HETEROCYCLES, Vol. 87, No. 1, 2013
85
These results suggest that the ethynyl group is reactive towards nucleophiles, in our case ethoxide or
methoxide, in a Michael addition-type reaction. Upon heating the acetal group cleaves off in a mechanism
unknown to us but most likely involves breaking of the required C-C bond through anomeric assistance of
an acetal group, as illustrated in Scheme 8. The leaving group is then the tautomer of the 6-methylpterin.
We found little precedent for this mechanism. In a possible related report, a methoxide nucleophile add to
a 6-ethynylpurine.11 The intermediate acetal, which was not isolated, then cleaves to give a
6-methylpurine.
Scheme 8
In conclusion, we have demonstrated that a 6-sulfonyloxypteridine 3 is a useful substrate for Sonogashira
coupling reactions using simple Pd catalyzed conditions.
EXPERIMENTAL
1
Melting points were obtained using a Stuart melting point apparatus, and are uncorrected. H and 13C
spectra were reported on Bruker Avance-300 spectrometer at 300 MHz. Chemical shifts are reported in
1
parts per million (ppm) relative to tetramethylsilane as internal standard (in the case of the H NMR at
13
7.27 ppm for CDCl3 and 2.45 ppm for DMSO, and in the case of C NMR at 77 ppm). Infrared spectra
were obtained on a Bruker Tensor 27 spectrometer. Samples were placed on a diamond thin film. The
absorptions are reported on the wave number (cm-1) scale, in the range 400 – 4000 cm-1. High resolution
mass spectra were recorded on a Thermo-Finigan DFS instrument. Data are quoted : m/z value (relative
abundance). Low resolution mass spectra were recorded on Thermo-Finigan LXQ instrument using either
atmospheric pressure chemical ionization (APCI) or electro spray ionization (ESI) techniques. HPLC was
run on a Thermo-Finigan instrument using a C18 (2) Phenomenex column with 150 x 4.60 mm
dimensions. The samples were eluted with a water-methanol solvent system over 10 min using a gradient
program: starting with 95% water for 2 min, changing to 100% methanol over the next 4 minutes and
running for 4 min with 100% methanol. Detection of eluting components was achieved by a photodiode
array and APCI-MS detector.
Synthesis of 2,4-diaminopteridin-6-one (1)8
In a 1L flask fitted with a stirrer bar, was added 2M H2SO4 (550 mL) and the flask warmed to 80 oC. To
the flask was added 2,4,5,6-tetraaminopyrimidine (21.17 g, 0.136 mol) and stirring continued for 10 min.

86
HETEROCYCLES, Vol. 87, No. 1, 2013
Glyoxylic acid (16.35 g, 0.272 mol, 2 eq.) was added, the solution stirred for a further 15 min then
allowed to cool to rt and left to stir for 2 h. The resultant suspension was filtered, and the mustard solid
washed with water (3 x 50 mL). The solid was suspended in water (150 mL) and neutralized with
saturated aqueous NaHCO3 (cautiously added in 10 mL portions until effervescence stopped, ca. ~150 mL
was required), the solid filtered and washed with water (5 x 60 mL) then MeOH (3 x 50 mL), air dried,
and then dried under reduced pressure over P2O5 to give 2,4-diaminopteridin-6-one (17.9 g, 74%) as a
o
mustard solid. mp (dec) >300 C; m/z (ESI) 179 (M+H+, 100); λmax (1M NaOH) 410 and 265 nm.
Physical and spectroscopic data agree with those reported elsewhere.8
Synthesis of 2,4-bis(N,N-dimethylaminomethyleneamino)pteridin-6-one (2)7
2,4-Diaminopteridin-6-one (4.02 g, 0.0225 mol) and Bredereck’s reagent9 (14 mL, 0.0675 mol, 3 eq.)
were stirred together in DMF (50 mL), under an Ar atmosphere and warmed to 65 oC for 3 h, and allowed
to cool to rt. The yellow precipitates were filtered, washed with little cold DMF then Et2O, air dried and
finally dried under reduced pressure over P2O5 to give 2,4-bis(N,N-dimethylaminomethyleneamino)-
pteridin-6-one (6.20 g, 91%); mp 270 oC (dec); δH (300 MHz, CDCl3) 3.07 (3H, s), 3.08 (3H, s), 3.10 (3H,
s), 3.15 (3H, s), 8.15 (1H, s), 8.48 (1H, s) and 8.76 ppm (1H, s); m/z (EI) 288 (M+, 100), 273 (45), 244
(19) and 232 (45). Spectroscopic data agree with those reported elsewhere.7
Synthesis of 2,4-bis(N,N-dimethylaminomethyleneamino)-6-benzenesulfonyloxypteridine (3)
2,4-Bis(N,N-dimethylaminomethyleneamino)pteridin-6-one (4.16 g, 14.5 mmol), DMAP (0.20 g, 1.45
mmol) and benzenesulfonyl chloride (3.8 mL, 29 mmol, 2 eq.) were dissolved in DCM (40 mL) and
o
cooled to 0 C. Et3N (3.7 mL, 29 mmol, 2 eq.) was added drop-wise into the mixture, and the final
solution was allowed to warm to rt and stirred for 1 h. The reaction was quenched with saturated aqueous
NaHCO3 (15 mL), the organic layer separated and the aqueous layer washed with DCM (2 x 20 mL). The
combined organic layers were dried over MgSO4, and the solvent evaporated to dryness to give a dark
yellow solid which was recrystallized from EtOH to give 2,4-bis(N,N-dimethylaminomethyleneamino)-6-
o
benzenesulfonyloxypteridine (4.62 g, 75%) as a yellow solid; mp 203 – 205 C (dec); δH (CDCl3, 300
MHz) 3.19 (3H, s), 3.22 (3H, s), 3.23 (3H, s), 3.30 (3H, s), 7.53 – 7.79 (3H, m), 8.25 – 8.28 (2H, dd, J =
7.8, 0.8 Hz), 8.56 (1H, s) and 8.95 – 8.97 ppm (2H, overlapping singlet); δC (CDCl3, 100 MHz) 35.4, 41.4,
125.2, 129.0, 129.4, 134.4, 136.3, 144.4, 148.6, 155.6, 158.3, 159.8, 166.5 and 168.5 ppm; m/z (EI) 428
(M+, 21%), 413 (40), 288.2 (100), 273.1 (45), 232 (40), 217 (80) and 162.9 (35) (HREI found: 428.13775.
32
C18H20N8O3 S requires 428.13791).
Synthesis of 4-amino-2-(N,N-dimethylaminomethyleneamino)-6-(phenylethynyl)pteridine (5)

HETEROCYCLES, Vol. 87, No. 1, 2013
87
In a 2-neck 50 mL round bottom flask, equipped with a magnetic stirrer bar and positive pressure of argon,
2,4-bis(N,N-dimethylaminomethyleneamino)-6-benzenesulfonyloxypteridine (1.00 g, 2.34 mmol),
PdCl2(PPh3)2 (80 mg, 0.11 mmol), phenylacetylene (350 µL, 2.808 mmol) and Et3N (0.5 mL, 4.68 mmol,
o
2 eq.) were dissolved in DMF (15 mL), warmed to 80 C and stirred for 2 h. The flask was cooled to rt,
filtered through celite, concentrated in vacuo and purified on flash silica (eluting with 5% MeOH/DCM)
to give two close running fractions (650 mg); m/z (APCI) 373 [M+H+, 60%], 318 [M-55, 70%]+; LCRT
7.01 and 7.05 min. Further purification of the close running fractions by flash chromatography on flash
silica gave 4-amino-2-(N,N-dimethylaminomethyleneamino)-6-(phenylethynyl)pteridine (550 mg, 74%) as
a yellow solid; mp 201 – 203 oC (dec); Rf 0.25; δH (DMSO-d6, 300 MHz) 3.01 (3H, s), 3.12 (3H, s), 7.46
– 7.51 (3H, m), 7.58 – 7.69 (2H, m), 8.03 (2H, broad s), 8.76 (1H, s) and 9.06 ppm (1H, s); m/z (EI) 317
(M+, 30%), 302 (50) and 262 (100) (HREI found: 317.13849. C17H15N7 requires 317.13889).
4-Amino-2-(N,N-dimethylaminomethyleneamino)-6-(trimethylsilylethynyl)pteridine (7)
In a 2-neck 50 mL round bottom flask, equipped with a magnetic stirrer bar and positive pressure of argon,
2,4-bis(N,N-dimethylaminomethyleneamino)-6-benzenesulfonyloxypteridine (1.0 g, 2.34 mmol),
PdCl2(PPh3)2 (80 mg, 0.11 mmol), TMS-Cl (395 µL, 2.808 mmol) and Et3N (0.5 mL, 4.68 mmol, 2 eq.)
were dissolved in DMF (15 mL), warmed to 80 oC and stirred for 2 h. The flask was cooled to rt, filtered
through celite, concentrated in vacuo and purified on flash silica (eluting with 5% MeOH/DCM) to give
two close running fractions (650 mg) as a dark yellow solid; m/z (APCI) 369 [M+H+, 45%], 314 [M-55]+;
LCRT 7.34 and 7.45 min. Further purification by flash chromatography on flash silica gave
4-amino-2-(N,N-dimethylaminomethyleneamino)-6-(trimethylsilylethynyl)pteridine (460 mg, 63%) as a
yellow solid; mp 253 oC (dec); Rf 0.29; δH (DMSO-d6, 300 MHz) 0.29 (9H, s), 3.23 (3H, s), 3.29 (3H, 1H),
8.88 (1H, s) and 9.03 ppm (1H, s); m/z (EI) 313 (M+, 90%), 298 (30), 269 (70), 258 (94), 243 (100) and
28
201 (40) (HREI Found: 313.14542. C14H19N7 Si requires 313.14712).
Synthesis of 2,4-bis(N,N-dimethylaminomethyleneamino)-6-(3-methoxyprop-1-yn-1-yl)pteridine (8)
In a 2-neck 50 mL round bottom flask, equipped with a magnetic stirrer bar and positive pressure of argon,
2,4-bis(N,N-dimethylaminomethyleneamino)-6-benzenesulfonyloxypteridine (1.0 g, 2.34 mmol),
PdCl2(PPh3)2 (80 mg, 0.11 mmol), propargyl alcohol (198 mg, 2.808 mmol) and Et3N (0.5 mL, 4.68
mmol, 2 eq.) were dissolved in 15 mL DMF, warmed to 80 oC and stirred for 2 h. The flask was cooled to
rt, filtered through celite, concentrated and purified on flash silica (eluting with 5% MeOH/DCM) to give
2,4-bis(N,N-dimethylaminomethyleneamino)-6-(3-methoxyprop-1-yn-1-yl)pteridine (500 mg, 63%) as a
yellow solid; mp 196 oC (dec); Rf 0.20; δH (CDCl3, 300 MHz) 3.19 – 3.22 (12H, overlapping s), 3.50 (3H,
s), 4.40 (2H, s), 8.88 (1H, s) and 9.01 – 9.03 ppm (2H, overlapping s); δC (CDCl3, 100 MHz) 35.4, 35.8,

88
HETEROCYCLES, Vol. 87, No. 1, 2013
41,4, 41.6, 58.0, 60.2, 84.2, 88.8, 123.5, 128.8, 135.1, 153.6, 158.5, 162.5, 167.1 and 168.6 ppm; m/z
(APCI) 341.2 [M + H+, 100%]; (HRESI found: 341.18460, C16H21N8O requires 341.1833).
Synthesis of 2,4-diamino-6-(phenylethynyl)pteridine (10)10
4-Amino-2-(N,N-dimethylaminomethyleneamino)-6-(phenylethynyl)pteridine (150 mg, 0.473 mmol) was
treated with 10 mL EtOH/1M NH3 (1:1) mixture, gently refluxed for 16 h, filtered, the solid washed
sequentially with water (5 mL), EtOH (5 mL) and Et2O (5 mL), and dried under Hi-vac. at 70 oC to give
2,4-diamino-6-(phenylethynyl)pteridine (95 mg, 77%) as a yellow solid; mp >300 oC (dec); δH (DMSO-d6,
300 MHz) 6.91 – 7.01 (2H, broad s), 7.46 – 7.48 (3H, m), 7.61 – 7.62 (2H, m), 7.84 – 7.87 (2H, broad s)
and 8.86 ppm (1H, s); m/z (APCI) 263.1 [M + H+, 100] (HRESI found: 263.10340, C14H10N6 requires
263.10397). Spectroscopic data agree with those reported elsewhere.10
Synthesis of 2,4-diamino-6-ethynylpteridine (11)
4-Amino-2-(N,N-dimethylaminomethyleneamino)-6-(trimethylsilylethynyl)pteridine (200 mg, 0.64
mmol) was suspended in 25% NH3 solution (10 mL) and gently refluxed for 18 h, filtered through celite,
o
concentrated to a small volume (ca.~3 mL), acidified with glacial AcOH (~1 mL) and stored at 2 C for
24 h. The precipitates were collected by centrifugation, washed sequentially with water (5 mL), acetone
(5 mL) and Et2O (5 mL) to give 2,4-diamino-6-ethynylpteridine (70 mg, 76%) as yellow solid; mp >300
oC (dec); vmax /cm-1 3410 (-NH), 3310 (-NH2), 3016, 2926; δH (DMSO-d6, 300 MHz) 7.09 – 7.11 (2H,
broad s), 7.95 – 8.17 (2H, broad s) and 9.16 ppm (1H, s); m/z (APCI) 186 [M + H+, 100]. Attempts to get
high resolution mass were unsuccessful in both HREI and HRESI instruments.
Synthesis of 2,4-diamino-6-(3-methoxyprop-1-yn-1-yl)pteridine (12)10
2,4-Bis(N,N-dimethylaminomethyleneamino)-6-(3-methoxyprop-1-yn-1-yl)pteridine (130 mg, 0.381
mmol) was dissolved in 8 mL EtOH/1M NH3 (1:1) mixture, gently refluxed for 8 h, allowed to cool to rt,
acidified with AcOH and stored at 2 oC for 24 h. The precipitates were filtered, washed sequentially with
o
water (5 mL), EtOH (5 mL) and Et2O (5 mL), and dried under High vac. at 60 C to give
2,4-diamino-6-(3-methoxyprop-1-yn-1-yl)pteridine (65 mg, 74%) as a yellow solid; mp >300 oC (dec); δH
(DMSO-d6, 300 MHz) 3.35 (3H, s), 4.40 (2H, s), 6.87 – 6.99 (2H, broad s), 7.83 (2H, broad s) and 8.74
ppm (1H, s); δC (DMSO-d6, 100 MHz) 57.2, 59.3, 83.4, 87.9, 122.5, 129.5, 152.6, 154.8, 163.4 and 172.3
ppm; m/z (APCI) 231 [M + H+, 100] (HRESI found: 231.0995, C10H10N6O requires 231.09888).
Spectroscopic data agree with those reported elsewhere.10
Synthesis of 6-(phenylethynyl)pterin (13)10

HETEROCYCLES, Vol. 87, No. 1, 2013
89
4-Amino-2-(N,N-dimethylaminomethyleneamino)-6-(phenylethynyl)pteridine (200 mg, 0.631 mmol) was
treated with 10 mL EtOH/1M NaOH (1:1) mixture, gently refluxed for 16 h, filtered through celite,
concentrated to small volume (~3 mL), acidified with AcOH (~1.5 mL), and stored at 2 oC for 18 h. The
yellow precipitates were collected by centrifugation, washed sequentially with water (5 mL), acetone (5
mL) and Et2O (5 mL), and dried under reduced pressure at 60 oC to give 6-(phenylethynyl)pterin (120 mg,
73%) as a yellow solid; mp >300 oC (dec); vmax /cm-1 1737 (C=O); δH (DMSO-d6, 300 MHz) 7.34 – 7.48
(3H, m), 7.63 (2H, m) and 8.72 ppm (1H, s); m/z (APCI) 264 [M + H+, 100] (HREI Found: 263.08092.
C14H9N5O requires 263.08071). Spectroscopic data agree with those reported elsewhere.10
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the National Research Foundation (NRF, South Africa), and
University of Witwatersrand for financial support.
REFERENCES
1. D. J. Brown, Heterocyclic compounds, Fused Pyrimidines, John Wiley and sons, 1988, pp. 1-4.
2. R. Purrmann, Justus Liebigs Ann. Chem., 1940, 544, 182.
3. E. C. Taylor and R. Kobylecki, J. Org. Chem., 1978, 43, 680.
4. T. Hanaya, H. Baba, and H. Yamamoto, Carbohyd. Res., 2007, 342, 2159.
5. S. Goswami and A. K. Adak, Tetrahedron Lett., 2002, 43, 8371.
6. E. C. Taylor, K. L. Perlman, I. P. Sword, M. Sequin-Frey, and P. A. Jacobi, J. Am. Chem. Soc., 1973,
95, 6407.
7. A. Dinsmore, D. C. Garner, and J. A. Joule, Tetrahedron, 1998, 54, 9559.
8. G. Konrad and W. Pfleiderer, Chem. Ber., 1970, 103, 735.
9. H. Bredereck, G. Simchen, H. Hoffman, P. Horn, and R. Wahl, Angew. Chem., 1967, 79, 311.
10. E. C. Taylor and P. S. Ray, J. Org. Chem., 1987, 52, 3997.
11. M. Kuchar, R. Pohl, I. Votruba, and M. Hocek, Eur. J. Org. Chem., 2006, 5083.