An electrochemical synthesis of functionalized arylpyrimidines from 4-Amino-6-Chloropyrimidines and aryl halides

Article abstract of DOI:10.3390/molecules16075550

A range of novel 4-amino-6-arylpyrimidines has been prepared under mild conditions by an electrochemical reductive cross-coupling between 4-amino-6-chloropyrimidines and functionalized aryl halides. The process, which employs a sacrificial iron anode in c

Full text of DOI:10.3390/molecules16075550

Molecules 2011, 16, 5550-5560; doi:10.3390/molecules16075550
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
An Electrochemical Synthesis of Functionalized
Arylpyrimidines from 4-Amino-6-Chloropyrimidines
and Aryl Halides
Stéphane Sengmany, Erwan Le Gall * and Eric Léonel *
Electrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris-Est (ICMPE), UMR
7182, CNRS, Université Paris-Est Créteil Val-de-Marne, 2-8 rue Henri Dunant, 94320 Thiais, France
* Authors to whom correspondence should be addressed; E-Mails: legall@icmpe.cnrs.fr (E.L.G.);
leonel@icmpe.cnrs.fr (E.L.); Tel.: +33-1-49-78-11-35 (E.L.G.); +33-1-49-78-11-36 (E.L.);
Fax: +33-1-49-78-11-48.
Received: 18 May 2011; in revised form: 1 June 2011 / Accepted: 21 June 2011 /
Published: 29 June 2011
Abstract: A range of novel 4-amino-6-arylpyrimidines has been prepared under mild
conditions by an electrochemical reductive cross-coupling between 4-amino-6-chloro-
pyrimidines and functionalized aryl halides. The process, which employs a sacrificial iron
anode in conjunction with a nickel(II) catalyst, allows the formation of coupling products
in moderate to high yields.
Keywords: cross-coupling; electrosynthesis; functionalized pyrimidines; nickel catalysis;
sacrificial anode process
1. Introduction
The mild and efficient formation of carbon-carbon bonds has always constituted one of the more
challenging areas of organic synthesis [1–5]. In this context, the synthesis of diazaaromatic compounds
by cross-coupling reactions has been the subject of a tremendous development over the past years. As
they represent important structures, widespread in many agrochemicals and biologically active
compounds [6–17], the preparation of substituted pyrimidines has attracted great attention of the
organic community. Therefore, many efforts have been devoted to the arylation of the pyrimidine ring

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unit by using mostly well established palladium- or nickel-catalyzed processes like the Kumada,
Suzuki, Stille, or Negishi couplings [18–21].
We reported recently the preparation of aryl- and heteroarylpyridazines by an electrochemical
cross-coupling procedure employing an iron sacrificial anode [22] and a nickel catalyst [23,24]. In
the continuation of this preceding work, we would like to report herein the extension of our
electrochemical procedure to the preparation in moderate to high yields of a range of novel 4-amino-6-
chloropyrimidines 3.
2. Results and Discussion
Although the preparation of substituted diazaaromatic compounds is of current general interest, we
were surprised by the lack of reports on the electrochemical arylation of amino chloropyrimidines. As
these compounds represent a relevant class of potent pharmacophores, we decided to turn our attention
to the synthesis of 4-amino-6-arylpyrimidines 3. The implementation of this study was additionally
motivated by interesting results, highlighted in our previous reports on the electrochemical arylation of
substituted halo-pyridazines, which had revealed the singular reactivity of these substrates. Indeed, it
was noticed (and was not explained to date) that the nature of the substituent was of great importance
over the coupling efficiency.
Consequently, we considered that these peculiar features should worth a further fundamental study
dedicated to the examination of 4-amino-6-chloropyrimidines behavior in electrochemical couplings.
The preparation of 4-amino-6-arylpyrimidines 3 was thus envisaged through a catalyzed reductive
cross-coupling reaction between 4-amino-6-chloropyrimidines 1 and aryl halides 2 (Scheme 1).
Scheme 1. Cross-coupling of 4-amino-6-chloropyrimidine with functionalized aryl halides.
To this end, we decided to employ an electrochemical method, based on the use of an iron sacrificial
anode, which had shown to provide very interesting results on similar reaction systems [25,26]. Few
4-amino-6-chloropyrimidines 1 being commercially available, a range of these starting compounds
was initially prepared in high yields by mono-amination of 4,6-dichloropyrimidine using standard
procedures [27]. For the implementation of the subsequent electrochemical coupling, preliminary
experiments indicated that the most efficient conditions are the following: the reaction is carried out
under an inert atmosphere of argon, in undivided cell fitted with an iron rod as the anode, a nickel
foam as the cathode, in DMF at room temperature in the presence of nickel bromide 2,2’-bipyridine
complex (NiBr2bpy) as the catalyst. As reported elsewhere, a pre-electrolysis in the presence of
a catalytic amount of 1,2-dibromoethane at 0.2 A during 15 minutes, as well as the use of an
overstoichiometric amount of the aromatic halide 2 versus the chloropyrimidine 1, are required for the

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efficiency of the coupling. A constant current of 0.2 A [28] is then applied until consumption of the
starting chloropyrimidine 1.
Using these conditions, 4-amino-6-chloropyrimidines 1 were subjected to electroreductive
cross-couplings with diversely functionalized aromatic halides 2. As they represent an appropriate
compromise between commercial availability, cost, and reactivity, bromides were generally used.
However, when functional groups borne by the phenyl moieties were electron-donating, fluorine, or
hydrogen, the corresponding aryl iodides were used instead of aryl bromides to limit the formation of
by-products under these conditions. Results are summarized in Table 1.
The cross-coupling proceeds in moderate to good yields. The nature (electron-donating,
electron-withdrawing, halide atoms) and the position (ortho, meta and para) of the substituents borne
by the phenyl do not have a notable influence on the coupling when aliphatic or alicyclic amines are
linked to the pyrimidine ring (Table 1, entries 1–4), except when the substituent of the phenyl is at the
ortho position. Indeed, in this case, the yield seems to be more limited, presumably due the steric
hindrance of the substituent (Table 1, entry 3).
Surprisingly, a similar decrease of the yields was also observed with chloropyrimidines substituted
at the 4-position by some aromatic amine such as imidazole, pyrrole or 4-methoxyaniline (Table 1,
entries 6, 7 and 8). In the case of imidazole and pyrrole (Table 1, entries 6 and 7), the moderate yields
can be attributed to a rapid consumption of a part of the starting chloropyrimidines 1 by dimerization,
despite the presence of an excess of the aryl halide in the medium. With 4-methoxyaniline as the amine
(Table 1, entry 8), the coupling reaction is very slow compared to side reactions, mainly corresponding
to the reduction of the aryl halide, even in the presence of a large excess of this latter. However, the
corresponding coupling product is of particular interest as the further deprotection of the PMP
group [29] should give rise to the formation of a –NH2 substituent at the 4-position. In addition, this
latter result is very encouraging since it constitutes, to the best of our knowledge, the first example of
an electrochemical cross-coupling involving a diazaaromatic substrate bearing an unprotected N-H
substituent. This is of particular significance for further potential transformations of the resulting
compounds by N-C bond formations. Additionally, it also constitutes an entry to even more interesting
stereoselective additions and functional group interconversions by using, for instance, α-amino esters
connected to the pyrimidine moiety. This assertion was partly verified by an experiment involving a
chloropyrimidine substituted with a secondary amino ester, L-proline methyl ester (Table 1, entry 9).
Although an only limited yield was obtained, this constituted the experimental evidence that the
aliphatic CO2Me group is compatible with this electrochemical process.
In all the cases, an excess of the aryl halide 2 was used to counterbalance the consumption of a part
of the halide by dimerization. Furthermore, it should be noted that for couplings where a rapid
consumption of aryl halide is observed (Table 1, entries 2, 3, 4, 8 and 9), either by reduction of
C-halogen bond into C-H, or by dimerization, one additional equivalent of aryl halide is introduced
during the reaction to drive the coupling to completion.

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Table 1. Cross-coupling of 4-amino-6-chloropyrimidines with various functionalized aryl halides.
Isolated
Entry
Substrate
Halide
Reaction Time
Product
Yield (%)
1
5 h
83
3a
3b
OHC
N
78a
N
N
2
5 h
Cl
N
3
4
6 h
48b
99b
3c
5 h 30
3d
5
6 h 30
77
3e
6
7
4 h 30
3 h 30
36
34
3f
3g
8
6 h 15
41b
41b
3h
9
6h
3i
a
b
After 4h of reaction, one more equivalent of ArX was added; After 2 h 30, one more equivalent of ArX
was added.

Molecules 2011, 16
5554
The mechanism of this cross-coupling reaction might be similar to those already described for this
type of electrochemical syntheses [23] (Scheme 2). Accordingly, the electrocatalytic cycle would be
initiated by a preliminary reduction of Ni(II) into Ni(0). At this stage, an oxidative addition of
Ni(0) into the C-X bond of either chloropyrimidine or aryl halide should be envisaged. A recent
electroanalytical work dedicated to the mechanistical investigation of cross-coupling reactions
involving chloropyridazine [24] has reported that the oxidative addition proceeds faster with the
chloropyridazine than with the aryl halide. This should also be likely the case with pyrimidines
derivatives, which should give rise to the formation of HetArNiIICl species. The monoelectronic
reduction of this complex should provide a HetArNiI species which might be involved in a further
oxidative addition onto the aryl halide, furnishing a HetArNiIII(Ar)X complex. A reductive elimination
on this latter should give rise to the formation of the final coupling product along with NiIX, allowing,
after electrochemical reduction, the recovery of Ni0 which can be reengaged in the catalytic cycle.
Scheme 2. Proposed reaction mechanism.
The efficiency of the procedure proved to be sensitive to the applied current intensity.
Consequently, a 0.2 A constant current intensity was found to be the best compromise in terms of
reaction efficiency and rapidity. Indeed, it is well recognized [28] that a lower intensity encourages a
metathesis of HetArNiIICl providing HetAr2NiII and NiCl2, which results in the partial loss of both the
catalyst and the heteroaromatic chloride by reductive elimination. On the contrary, a higher intensity
promotes the reduction of HetArNiIICl into HetArNiI and Cl−, thus encouraging the formation of
HetArNiIII(Ar)X by a further Ni(I) insertion into the C-X bond of ArX, which is the desired pathway of
the reaction.

Molecules 2011, 16
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3. Experimental
3.1. General
Solvents and reagents were purchased from commercial suppliers and used without further
purification. Nickel bromide 2,2’-bipyridine complex (NiBr2bpy) was prepared from nickel bromide
hydrate and 2,2’-bipyridyl [30]. Reactions were monitored by gas chromatography (GC) using a
Varian 3900 chromatograph fitted with an SGE capillary column (l = 5m, Ø = 0.32mm, df = 0.5µm).
Melting points were measured on a Büchi B-545 apparatus. Infrared spectra were recorded in ATR
mode on a Bruker TENSOR 27 spectrometer and treated via OPUS software. NMR spectra were
recorded in CDCl3 at 400 MHz (1H), 100 MHz (13C) and 376 MHz (19F) on a Bruker Avance II 400
spectrometer. Chemical shift (δ) are reported in parts per million (ppm) relative to the residual solvent
signal. Coupling constant values (J) are given in Hertz (Hz) and refer to apparent multiplicities,
indicated as follows: s (singlet), d (doublet), t (triplet, q (quartet), m (multiplet). Mass spectra (in
electronic impact (EI+) ionization mode) were measured on a Thermo Scientific ITQ 700 GC-MS
spectrometer fitted with a Varian column (l = 25m, Ø = 0.25mm, df = 0.25µm). High Resolution Mass
Spectra (HRMS) were performed in positive Electrospray Ionisation (ESI+) mode by the Mass
Spectrometry service of the ICOA (Institut de Chimie Organique et Analytique), Orléans, France.
Purifications were performed by flash chromatography on silica gel (granulometry 70–200 µm).
Compounds which have been previously described in the literature are linked to the corresponding
bibliographic references whereas compounds labelled by asterisk (*) are, to the best of our knowledge,
new compounds. The asterisk does not correspond to a footnote
3.2. Typical Procedure for the Cross-Coupling Reactions
To an undivided electrochemical cell, fitted by an iron rod as the anode and surrounded by a nickel
foam as the cathode, were added DMF (50 mL), tetra-n-butylammonium bromide (0.5 mmol, 400 mg),
and 1,2-dibromoethane (2.6 mmol, 215 µL). The mixture was electrolyzed under argon at a constant
current intensity of 0.2 A for 15 min at room temperature. Then the current was stopped, and NiBr2bpy
(0.5 mmol, 187 mg), the 4-amino-6-chloropyrimidine 1 (4 mmol), and the substituted aromatic halide
(8 mmol) were sequentially added. The solution was electrolyzed at 0.2 A until the starting 4-amino-6-
chloropyrimidine was totally consumed (3h30–6h). A saturated EDTA solution (50 mL) was added,
and the resulting solution extracted with CH2Cl2 containing 2–5% of methanol (4 × 50 mL). The
combined organic layers were dried over MgSO4, filtered, and evaporated under vacuum. The crude
product was purified by flash chromatography on silica (granulometry 70-200 µm), eluted with a
gradient mixture of solvents (pentane/Et2O, or pentane/acetone for some polar cross-coupling
compounds).
Ethyl 4-(6-morpholinopyrimidin-4-yl)benzoate* (3a). White crystals. mp: 130–131 °C (pentane/diethyl
1
ether). ATR-FTIR (neat, cm−1): 2955, 2862, 1702, 1587, 1570, 1277, 1245, 1109, 983. H-NMR
(400 MHz): δ 8.72 (s, 1H), 8.13 (d, J = 8.3 Hz, 2H), 8.03 (d, J = 8.3 Hz, 2H), 6.91 (s, 1H), 4.41 (q,
J = 7.2 Hz, 2H), 3.82 (t, J = 4.9 Hz, 4H), 3.72 (t, J = 4.9 Hz, 4H), 1.42 (t, J = 7.2 Hz, 3H). 13C-NMR
(100 MHz): δ 164.3, 160.8, 160.5, 156.7, 140.2, 129.9, 128.1, 125.0, 97.2, 64.6, 59.3, 42.3, 12.5. MS,

Molecules 2011, 16
5556
m/z (%): 314 (16), 313 ([M].+, 81), 312 (40), 285 (7), 284 (15), 283, (46), 282 (100), 270 (31), 269
(13), 268 (38), 257 (13), 256 (63), 255 (33), 254 (19), 240, (13), 228 (23), 210 (9), 155 (11), 146 (8),
128 (9). HRMS Calcd. for C17H20N3O3 [M+H]+: 314.14492, found [M+H]+: 314.14997.
4-[6-(3-Chlorophenyl)pyrimidin-4-yl]piperazine-1-carbaldehyde* (3b). Pale yellow amorphous solid.
mp: 123–125 °C (pentane/acetone). ATR-FTIR (neat, cm−1): 2859, 1664, 1587, 1567, 1434, 1228, 981,
1
695. H-NMR (400 MHz): δ 8.72 (s, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 7.86 (d, J = 7.1 Hz, 1H),
7.44–7.39 (m, 2H), 6.89 (s, 1H), 3.86-3.83 (m, 2H), 3.75–3.71 (m, 2H), 3.71–3.67 (m, 2H), 3.53–3.49
(m, 2H). 13C-NMR (100 MHz): δ 162.5, 162.4, 160.9, 158.5, 139.7, 134.9, 130.2, 130.1, 127.1, 125.1,
98.8, 45.0, 44.5, 43.6, 39.7. MS, m/z (%): 304 (11), 303 (8), 302 ([M].+, 33), 301 (9), 246 (9), 245 (7),
244, (24), 234 (27), 233 (25), 232 (46), 231 (72), 230 (42), 221 (5), 220 (32), 219 (15), 218 (100), 208
(7), 207 (6), 206 (15), 190 (6), 189 (6), 162 (13), 155 (6), 138 (6), 136 (13), 127 (12), 68 (5). HRMS
Calcd. for C15H16ClN4O [M+H]+: 303.10072, found [M+H]+: 303.10078.
4-[2-Methoxyphenyl)-6-(piperidin-1yl)pyrimidine* (3c). Brown oil. ATR-FTIR (neat, cm−1): 2934,
2852, 1585, 1572, 1492, 1240, 1023, 979, 752. 1H-NMR (400 MHz): δ 8.60 (s, 1H), 7.74 (d, J = 7.2 Hz,
1H), 7.29 (t, J = 7.5 Hz, 1H), 7.02-6.96 (m, 2H), 6.91 (d, J = 8.1 Hz, 1H), 3.79 (s, 3H), 3.59–3.55
13
(m, 4H), 1.64-1.54 (m, 6H). C-NMR (100 MHz): δ 161.8, 161.3, 158.1, 157.3, 130.8, 130.5, 127.9,
121.0, 111.5, 103.3, 55.8, 45.1, 25.5, 24.7. MS, m/z (%): 270 (14), 269 ([M].+, 92), 268 (100), 241
(20), 240 (52), 226 (11), 225 (21), 224 (27), 223 (12), 214 (12), 213 (14), 212 (6), 211 (11), 210 (14),
199 (8), 198 (10), 197 (20), 196 (7), 186 (7), 185 (12), 184 (6), 183 (6), 171 (6), 164 (14), 157 (6), 156
(8), 131 (18), 84 (8). HRMS Calcd. for C16H20N3O [M+H]+: 270.16009, found [M+H]+: 270.16026
N,N-Diethyl-6-(meta-tolyl)pyrimidin-4-amine* (3d). Colourless oil. ATR-FTIR (neat, cm−1): 2972,
2928, 1577, 1509, 1352, 1255, 1026, 980, 791. 1H-NMR (400 MHz): δ 8.69 (s, 1H), 7.81 (s, 1H), 7.73
(d, J = 7.5 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.26 (d, J = 7.5 Hz, 1H), 6.74 (s, 1H), 3.60 (q, J = 7.0 Hz,
4H), 2.44 (s, 3H), 1.25 (t, J = 7.1 Hz, 6H). 13C-NMR (100 MHz): δ 162.8, 161.3, 158.5, 138.5, 138.4,
130.6, 128.5, 127.6, 123.9, 98.1, 42.3, 21.5, 12.8. MS, m/z (%): 242 (15), 241 ([M].+, 74), 240 (14),
226 (26), 213 (17), 212 (100), 199 (9), 198 (62), 197 (8), 142 (7), 116 (7), 115 (18). HRMS Calcd. for
C15H20N3 [M+H]+: 242.16517, found [M+H]+: 242.16525.
1-[6-(3-(Trifluoromethyl)phenyl)pyrimidin-4-yl]indoline* (3e). Pale yellow amorphous solid. mp:
154–155 °C (pentane/diethyl ether). ATR-FTIR (neat, cm−1): 3044, 2931, 1573, 1496, 1261, 1113,
1092, 1071, 754, 668. 1H-NMR (400 MHz): δ 8.90 (s, 1H), 8.48 (d, J = 7.5 Hz, 1H), 8.31 (s, 1H), 8.22
(d, J = 7.1 Hz, 1H), 7.75 (d, J = 7.2 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.29–7.23 (m, 2H), 7.01 (t,
J = 7.1 Hz, 1H), 6.96 (s, 1H), 4.12 (t, J = 8.3 Hz, 2H), 3.29 (t, J = 8.3 Hz, 2H). 13C-NMR (100 MHz): δ
161.8, 159.8, 158.3, 143.3, 138.7, 131.9, 131.4 (q, J = 30.0 Hz), 130.2, 129.3, 127.5, 126.8, 124.9,
123.9, 122.7, 116.3, 100.7, 48.7, 27.5. 19F-NMR (376 MHz): δ −62.7. MS, m/z (%): 342 (19), 341
([M].+, 100), 340 (89), 325 (14), 213 (7), 170 (8), 118 (27), 117 (6), 91 (5). HRMS Calcd. for
C19H15F3N3 [M+H]+: 342.12126, found [M+H]+: 342.12134.
4-(1H-Imidazol-1yl)-6-(4-methoxyphenyl)pyrimidine* (3f). Pale yellow amorphous solid. mp:
183.5–184.5 °C (pentane/acetone). ATR-FTIR (neat, cm−1): 2931, 1585, 1485, 1247, 1173, 1023, 832,

Molecules 2011, 16
5557
580. 1H-NMR (400 MHz): δ 9.05 (s, 1H), 8.53 (s, 1H), 8.11 (d, J = 8.8 Hz, 2H), 7.76 (s, 1H), 7.58 (s,
1H), 7.26 (s, 1H), 7.05 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H). 13C-NMR (100 MHz): δ 166.3, 162.6, 159.1,
155.6, 135.2, 131.6, 128.9 128.4, 115.7, 114.5, 102.8, 55.5. MS, m/z (%): 253 (17), 252 ([M].+, 100),
251 (6), 226 (21), 225 (30), 210 (13), 182 (6), 158 (5). HRMS Calcd. for C14H13N4O [M+H]+:
253.10839, found [M+H]+: 253.10837.
4-(4-Fluorophenyl)-6-(1H-pyrrol-1-yl)pyrimidine* (3g). White crystals. mp: 83–84 °C (pentane/diethyl
ether). ATR-FTIR (neat, cm−1): 3129, 3058, 1587, 1585, 1552, 1483, 1221, 1061, 832, 753, 571.
1H-NMR (400 MHz): δ 9.01 (s, 1H), 8.13-8.10 (m, 2H), 7.65–7.63 (m, 2H), 7.53 (s, 1H), 7.26–7.20
13
(m, 2H), 7.46-7.42 (m, 2H). C-NMR (100 MHz): δ 164.8 (d, J = 252.2 Hz), 164.7, 159.0, 157.5,
132.8 (d, J = 2.8 Hz), 129.3 (d, J = 8.7 Hz), 118.1, 116.1 (d, J = 21.8 Hz), 113.0, 102.6. 19F-NMR (376
MHz): δ -109.0. MS, m/z (%): 240 (16), 239 ([M].+, 100), 238 (17), 213 (20), 212 (37), 211 (11), 146
(9), 126 (10). HRMS Calcd. for C14H11FN3 [M+H]+: 240.09315, found [M+H]+: 240.09316.
N-(4-Methoxyphenyl)-6-phenylpyrimidin-4-amine (3h) [31]. Pale yellow crystals. mp: 150–151 °C
(pentane/diethyl ether). ATR-FTIR (neat, cm−1): 3236, 2995, 1587, 1569, 1505, 1411, 1241, 1033,
1
990, 828, 767, 688, 609. H-NMR (400 MHz): δ 8.71 (s, 1H), 7.94–7.91 (m, 2H), 7.85 (s, 1H),
7.7–45–7.43 (m, 3H), 7.32–7.28 (m, 2H), 6.99–6.96 (m, 3H), 3.86 (s, 3H). 13C-NMR (100 MHz):
δ 163.7, 162.6, 158.8, 157.6, 137.6, 130.8, 130.3, 128.7, 126.9, 125.6, 114.9, 99.0, 55.6. MS, m/z (%):
278 (19), 277 ([M].+, 100), 276 (67), 263 (9), 262 (50), 261 (7), 235 (5), 234 (10), 207 (5), 128 (11),
108 (10). HRMS Calcd. for C17H16N3O [M+H]+: 278.12879, found [M+H]+: 278.12892.
(S)-Methyl 1-[6-(3-cyanophenyl)pyrimidin-4-yl]pyrrolidine-2-carboxylate* (3i). Pale yellow
amorphous solid. mp: 102-106 °C (pentane/diethyl ether). ATR-FTIR (neat, cm−1): 2952, 2875, 2359,
2229, 1739, 1587, 1502, 1207, 1168, 798, 693, 675. 1H-NMR (400 MHz): δ 8.57 (s, 1H), 8.20 (s, 1H),
8.14 (d, J = 7.0 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 6.64 (s, 1H), 4.67 (broad s,
13
1H), 3.69 (s, 4H), 3.48 (broad s, 1H), 2.28-2.25 (broad m, 1H), 2.12-2.08 (broad m, 3H). C-NMR
(100 MHz): δ 173.3, 160.4, 158.5, 139.3, 133.2, 131.2, 130.7, 129.6, 118.5, 113.0, 99.5, 59.4, 52.4,
46.8, 29.8, 24.0. MS, m/z (%): 308 ([M].+, 14), 250 (17), 249 (100), 153 (8). HRMS Calcd. for
C17H17N4O2 [M+H]+: 309.13460, found [M+H]+: 309.13467.
4. Conclusions
In summary, we report in this paper the nickel-catalyzed electrochemical cross-couplings of a range
of 4-amino-6-chloropyrimidines with diversely substituted aryl halides. The method provides an
efficient entry to some novel 4-amino-6-arylpyrimidines, in satisfactory to high yields. The great
functional tolerance of the reaction, as well as the possibility of engaging chloropyrimidines bearing
N-H derivatives in the coupling, opens the way to further subsequent transformations by N-C
couplings and functional group interconversions. The extension of the reaction to heteroaromatic
halides in currently in progress and will be reported in due course.

Molecules 2011, 16
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