A practical synthesis of substituted 2,6-diaminopyridines via microwave-assisted copper-catalyzed amination of halopyridines

Article abstract of DOI:10.1016/j.tet.2015.08.042

A microwave assisted copper-catalyzed amination protocol is reported utilizing a series of 2,6-dihalo- and 2-amino-6-halo pyridine precursors. Using this procedure, selective substitution of one or two halogens by aryl or alkylamines was achieved within 2-6 h with temperatures between 80 and 225 °C affording 2,6-diaminopyridines in good to excellent isolated yields. The reaction allows easy variation between educts and different N-substitutions. The target compounds are valuable precursors for the synthesis of bis-phosphorylated 2,6-diaminopyridines which are used as PNP pincer ligands in transition metal complexes.

Full text of DOI:10.1016/j.tet.2015.08.042

Accepted Manuscript
A practical synthesis of substituted 2,6-diaminopyridines via microwave-assisted
copper-catalyzed amination of halopyridines
Matthias Mastalir, Egon E. Rosenberg, Karl Kirchner
PII:
S0040-4020(15)01234-X
10.1016/j.tet.2015.08.042
TET 27064
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 July 2015
Revised Date: 11 August 2015
Accepted Date: 16 August 2015
Please cite this article as: Mastalir M, Rosenberg EE, Kirchner K, A practical synthesis of substituted
2,6-diaminopyridines via microwave-assisted copper-catalyzed amination of halopyridines, Tetrahedron
(2015), doi: 10.1016/j.tet.2015.08.042.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
TOC
A practical synthesis of substituted 2,6-diaminopyridines via microwave-
assisted copper-catalyzed amination of halopyridines
A microwave assisted copper-catalyzed amination protocol is reported utilizing a series of 2,6-dihalo-
and 2-amino-6-halo pyridine precursors to yield 2,6-diaminopyridines in good to excellent yields.

1
ACCEPTED MANUSCRIPT
A practical synthesis of substituted 2,6-diaminopyridines via microwave-
assisted copper-catalyzed amination of halopyridines
a
b
, a
Matthias Mastalir, Egon E. Rosenberg, Karl Kirchner*
a
Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, 1060
Vienna, Austria
b
Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9,
A-1060 Vienna, AUSTRIA
Abstract
A microwave assisted copper-catalyzed amination protocol is reported utilizing a series of 2,6-dihalo-
and 2-amino-6-halo pyridine precursors. Using this procedure, selective substitution of one or two
o
halogens by aryl or alkylamines was achieved within 2-6 h with temperatures between 80-225 C
affording 2,6-diaminopyridines in good to excellent isolated yields. The reaction allows easy variation
between educts and different N-substitutions. The target compounds are valuable precursors for the
synthesis of bis-phosphorylated 2,6-diaminopyridines which are used as PNP pincer ligands in
transition metal complexes.
Keywords: Aminations, 2,6-diaminopyridines, nucleophilic aromatic substitutions, heterocycles,
microwave assisted reactions, copper catalyzed
________________
*
Corresponding author. Tel.: +43 1 58801 163611; Fax.: +43 1 58801 16299; E-mail:
kkirch@mail.tuwien.ac.at (Karl Kirchner)

2
ACCEPTED MANUSCRIPT
1. Introduction
The 2,6-diaminopyridine molecule is a useful scaffold for the design of tridentate ligands in
coordination and organometallic chemistry, agrochemicals, dyes, and pharmacologically potent
1
,2,3,4,5,6
building blocks.
catalysed by copper, copper salts or proline
Kempe et al. developed an Ir-catalyzed protocol for both symmetrically and non-symmetrically N,N’-
The most frequently applied methods are nucleophilic substitutions often
7,8,9
10,11,12,13,14
and Buchwald-Hartwig aminations.
Recently,
15
dialkylated 2,6-diaminopyridines from 2,6-diaminopyridine and alcohols. All methods basically yield
the 2,6-diaminopyridines and it depends on the specific target which one performs better.
In recent years we have been focusing on the chemistry of transition metal complexes bearing
16
PNP pincer ligands based on the 2,6-diaminopyridine scaffold. In these PNP ligands the central
pyridine ring contains -NRPR’ (R‘ = H, alkyl, R = alkyl, aryl) substituents in the two ortho positions.
2
This methodology was first developed for the synthesis of N,N'-bis(diphenylphosphino)-2,6-
17
diaminopyridine (PNP-Ph). In these ligands the aromatic pyridine ring and the phosphine moieties
are connected via NH, N-alkyl, or N-aryl linkers (Scheme 1). Accordingly, the development of a simple
general method for the selective formation of N,N’-disubstituted 2,6-diamino pyridines is of great
importance for the design of new PNP ligands. It has to be noted that most substituted 2,6-
diaminopyridines are commercially not available.
Scheme 1
Here we describe a simple microwave assisted copper catalyzed amination protocol utilizing various
2,6-dihalo- and 2-amino-6-halo pyridine precursors I-VII as shown in Scheme 2. This simple procedure
permits the selective substitution of one or two halogens by primary and secondary aryl and
alkylamines in a relatively short time to afford a series of 2-amino- and/or 2,6-diaminopyridines in high
isolated yields. This methodology constitutes a practical alternative to other methods.

3
ACCEPTED MANUSCRIPT
R
1
2
R R NH
CuI (1.2 mol%)
R1
R1
I-VII
N
R2
N
N
R2
µW, 80 - 225 °C
NH2
Br
Cl
N
Cl
Br
N
Br Br
N
NH
2
Br
N
I
II
III
IV
NHAc
Br
NO2
CN
CN
Cl
Br
N
Cl
N
Cl
H N
N
2
VII
V
VI
Scheme 2
Results and discussion
Treatment of compounds I-VII (4.2 mmol) with various primary and secondary amines in the
presence of catalytic amounts of CuI (1.2 mol%) and traces of water (100µL) afforded selectively
mono or disubstituted aminopyridines depending on the reaction conditions (Table 1). The addition of
small amounts of water was necessary in order to achieve the required temperature under microwave
conditions. None of these reactions required any additional organic solvents.
Table 1. Synthesis of N-substituted and N,N’ disubstituted amino pyridines
Entry Reactant Product
t
[
T
[ °C ]
Yield
[%]
h]
1
2
3
4
I
2
4
4
2
180
180
180
180
94
82
78
93
N
N
Cl
H
I
N
N
Cl
H
N
N
I
N
N
Cl
Cl
II
N
N
N
H
H

4
ACCEPTED MANUSCRIPT
5
6
7
8
9
1
1
1
1
II
II
II
II
II
II
II
II
II
2
3
5
4
4
5
4
4
3
180
150
180
200
200
200
210
210
210
90
83
63
75
73
61
85
84
88
N
N
N
H
H
N
N
Br
H
N
N
N
H
H
N
H
N
N
H
C H
C H
8
17
8
17
N
N
N
H
H
0
1
2
3
N
N
N
H
H
N
N
N
H
H
N
N
N
H
H
N
H
N
N
H
1
4
5
II
II
6
6
225
225
43
19
N
H
N
N
H
1
N
H
N
N
H
16
II
3
160
82
N
H
N
Br

5
ACCEPTED MANUSCRIPT
N
N
Br
17
18
19
20
21
22
23
24
25
26
27
28
II
30
4
140
180
190
160
150
150
160
150
160
165
135
130
92
78
78
83
62
95
83
96
78
75
93
97
II
N
N
N
II
4
N
N
N
III
III
III
17
17
IV
V
5
H N
N
N
N
2
H
8
H N
N
H
2
5
H N
N
N
2
5
N
H
N
N
5
N
N
N
NH2
Br
4
N
N
O
NH
4
N
H
N
N
H
NO2
NH2
VI
VII
3
H N
N
2
NC
CN
1.5
H N
N
NH2
2

6
ACCEPTED MANUSCRIPT
NC
CN
2
9
0
VII
VII
1
1
80
80
69
72
H N
N
N
H
2
NC
CN
3
H N
N
N
H
2
In general, the reactions of amines with 2,6-dichoropyridine (I) led to the exclusive formation of
mono substituted products 1-3 in good to excellent isolated yields. It has to be noted, that even at
higher temperatures the formation of disubstituted products was not observed. In the case of
piperazine, both amine sites reacted with I and no mono substituted piperazine derivative was formed
(
entry 3). With 2,6-dibromopyridine (II), on the other hand, depending on the reaction temperature both
mono and the desired disubstituted products were obtained in high yields (entries 4,5, 7 - 19) and
showed a good substrate scope. Alkyl, aryl and benzylamines reacted readily to form compounds 4-
15. The use of chiral amines R- and S-1-phenylethane amine, allowed the preparation of chiral 2,6-
diaminpyridnes (entries 11 and 12). By lowering the temperature also mono substituted
aminopyridines could be obtained. This has been exemplarily shown for isopropylamine. Compound 6
could be obtained selectively (entry 6) which is an interesting building block for mixed
diaminopyridines. In the case of anilines (entries 14 and 15) the reaction required a small amount of
Pd(PPh ) as co-catalyst (0.2 mol%) and the yields were rather low. In this particular case, other
3
4
1
8,19,20
established methods achieve much high yields.
Surprisingly, under the standard reaction
conditions allyl amine and N,N-methylbenzylamine reacted only to yield the mono substituted
compounds 16 and 17. With benzylamine no identifiable products could be isolated. At higher reaction
temperatures decomposition to intractable materials took place. The formation of compounds 18 and
19 demonstrates that also with secondary amines and II directly 2,6-diaminopyridines can be obtained.
Precursors III and 17 were utilized as entries into mixed 2,6-diaminopyridines (entries 20-24). Finally
we tested mono and dichloro and bromopyridines bearing both activating and deactivating groups (IV-
VII) as synthetic entry into mixed 2,6-diaminopyridines (entries 25-30). Deactivating groups from VI
and VII led to faster and better conversion under milder conditions. Moreover, the amination in the
case of chlorides was faster and proceeded at much lower temperatures as compared to the bromide
precursors (entries 27-30). Also the amination of VI and VII with aqueous ammonia to yield 27 and 28
worked very well with 93 and 97% isolated yields (entries 27 and 28). Compounds 25-30 are
particularly interesting since the functional groups may allow cleavage or conversion into other
functionalities. It has to be mentioned that all functionalized systems were less air sensitive than the
diamines lacking additional substituents in the pyridine ring.
3. Conclusion
A microwave assisted copper-catalyzed amination protocol is reported utilizing a series of 2,6-dihalo-
and 2-amino-6-halo pyridine precursors. With the exception of NH , methyl- and ethylamine, where
3

7
ACCEPTED MANUSCRIPT
aqueous solutions were used, the reaction is basically solvent free and only traces of water were
added to achieve the required temperatures under microwave conditions. This protocol generally
afforded the corresponding products in good yields with easy purification steps. Using this procedure,
selective substitution of one or two halogens by aryl- or alkylamines was achieved within 2-6 h at
o
temperatures between 80-225 C affording 2,6-diaminopyridines in good to excellent isolated yields.
The target compounds are valuable precursors for the synthesis of bis-phosphorylated 2,6-
diaminopyridines which are used as PNP pincer ligands in transition metal complexes.
4
. Experimental section
.1. General notes
4
Unless otherwise noted, chemicals were purchased from commercial suppliers and were used without
2
1,22,23
further purification. Precursors III, IV, V and VII where synthesized according to the literature.
Microwave reactions were performed on a CEM Explorer PLS microwave unit. Column
chromatography was performed on silica gel 60 from Merck. For thin layer chromatography (TLC)
aluminum backed silica gel was used. Melting points were determined using a Kofler-type Leica Galen
III micro hot stage microscope and are uncorrected. All samples were analyzed by LC-IT-TOF-MS in
1
the positive ion detection mode with the recording of MS and MS/MS spectra. Room temperature H
1
3
1
and C{ H} NMR spectra were recorded on Bruker DXP 200 and AVANCE-250 spectrometers and
were referenced internally to residual protio-solvent, and solvent resonances, respectively, and are
reported relative to tetramethylsilane (δ = 0 ppm).
4.2. Typical experimental procedure for the synthesis of N-alkyl and N-aryl 2,6-diamino
pyridines
Compounds I-VII (4.22 mmol), catalytic amounts of CuI (10 mg, 0.052 mmol) and water (100 µL) were
treated with 6 equivs. of the respective amine and sealed in a 5 mL microwave vial. Pd(PPh ) (10 mg,
3
4
0.008 mmol) was added in the case of anilines. After the reaction was completed (see Table 1), 2
equivs of solid K CO were added. The resulting product was obtained after filtration and washing with
2
3
water as an analytically pure crystalline solid. Otherwise all volatiles were then evaporated and purified
by flash column chromatography (A) or bulb-to-bulb distillation (B). In the case of methylamine and
ethylamine the corresponding aqueous solution was used without extra water addition.
4.2.1. (6-Chloropyridine-2-yl)-methyl-amine (1). Prepared according to general procedure A with 3
1
equivs of methylamine. Product was obtained as white crystals. Mp: 59-60 °C. H NMR (DMSO-d ) δ:
6
7.36 (dd, J = 8.3 Hz, J = 7.3 Hz, 1H, Py), 6.88 (bq, 1H, NH), 6.48 (d, J = 7.3, 1H, Py), 6.38 (d, J = 8.3
1
3
1
Hz, 1H, Py), 2.72 (d, 3H, CH3). C{ H} NMR (DMSO-d ) δ: 159.6 (Py), 148.5 (q, Py), 139.3 (Py), 109.6
6
+
(
Py), 105.9 (Py), 27.7 (CH ). HRMS (ESI): [M+H] , found 143.0374. C H N Cl requires 143.0371.
3
6
7
2
4.2.2. (6-Chloropyridine-2-yl)-isopropyl-amine (2). Prepared according to general procedure A with 3
1
equivs of isopropylamine. Product was obtained as yellow oil. H NMR (DMSO-d ) δ: 7.36 (t, J = 7.8
6
Hz, 1H, Py), 6.70 (br, 1H, NH), 6.38 (d, J = 7.2 Hz, 1H, Py), 6.33 (d, J = 8.0 Hz, 1H, Py), 3.9 (sept, 1H,
1
3
1
CH), 1.10 (d, J = 6.5 Hz, 6H, CH3). C{ H} NMR (DMSO-d ) δ: 159.6 (q, Py), 148.5 (q, Py), 139.3
6

8
ACCEPTED MANUSCRIPT
+
(
Py), 109.6 (Py), 105.9 (Py), 27.8 (CH ). HRMS (ESI): [M+H] , found 171.0680. C H N Cl requires
3
8
11
2
171.0684.
4.2.3. 1,4-Bis-(6-chloropyridine-2-yl)-piperazine (3). Prepared according to general procedure. The
1
product precipitated as colorless crystals from the reaction mixture. Mp: 139-140 °C . H NMR (DMSO-
d6) δ: 7.6 (t, J = 7.8 Hz, 2H, Py), 6.8 (d, J = 8.5 Hz, 2H, Py), 6.68 (d, J = 7.3 Hz, 2H, Py), 3.60 (s, 8H,
1
3
1
CH2). C{ H} NMR (DMSO-d ) δ: 158.6 (Py), 148.1 (q, Py), 140.6 (Py), 111.6 (Py), 105.4 (Py), 43.8
6
+
24
(
CH ). HRMS (ESI): [M+H] , found 309.0680. C H N Cl requires 309.0668.
2 14 14 4 2
4.2.4. N,N'-Dimethyl-2,6-diaminopyridine (4). Prepared according to general procedure B. Product was
1
obtained as beige crystals. Mp: 60-63 °C . H NMR (DMSO-d ) δ: 7.02 (t, J = 7.9 Hz, 1H, Py), 5.78 (br,
6
1
3
1
J = 3.4 Hz, 2H, NH), 5.52 (d, J = 7.9 Hz, 2H, Py), 2.64 (d, J = 4.9 Hz, 6H, CH3). C{ H} NMR (DMSO-
+
d ) δ: 159.1 (Py), 138.1 (Py), 93.8 (Py), 28.5 (CH ). HRMS (ESI): [M+H] , found 138.1036. C H 1N
6
3
7
1
3
1
8
requires138.1026.
4.2.5. N,N'-Diethyl-2,6-diaminopyridine (5). Prepared according to general procedure B. Product was
1
obtained as yellow oil. H NMR (DMSO-d ) δ: 6.97 (t, J = 8.0 Hz, 1H, Py), 5.73 (t, J = 4.8 Hz, 2H, NH),
6
1
3
1
5
.51 (d, J = 7.7 Hz, 2H, Py), 3.12 (m, 4H, CH ), 1.06 (t, J = 7.1 Hz, 6H, CH ). C{ H} NMR (DMSO-d )
2
3
6
+
δ: 158.5 (Py), 138.0 (Py), 94.2 (Py), 35.9 (CH ), 15.4 (CH ). HRMS (ESI): [M+H] , found 166.1351.
2
3
2
5
C H N requires 166.1339.
9
15
3
4.2.6. (6-Bromopyridin-2-yl)-isopropyl-amine (6). Prepared according to general procedure A with 3
1
equivs of methylamine. Product was obtained as yellow oil. H NMR (DMSO-d ) δ: 7.22 (t, J = 7.8 Hz,
6
1H, Py), 6.6 (s, 1H, NH), 6.6 (d, J = 7.3 Hz, 1H, Py), 6.4 (d, J = 8.0 Hz, 1H, Py), 3.9 (m, 1H, CH), 1.12
1
3
1
(
d, J = 6.5 Hz, 6H, CH3). C{ H} NMR (DMSO-d ) δ: 158.4 (Py), 139.5 (Py), 139.0 (Py), 139.2 (Py),
6
+
1
13.3 (Py), 106.7 (Py), 41.8 (CH), 22.3 (CH ). HRMS (ESI): [M+H] , found 215.0187. C H N Br
3
8
11
3
2
6
requires 215.0178.
4.2.7. N,N'-Diisopropyl-2,6-diaminopyridine (7). Prepared according to general procedure B. Product
1
was obtained as yellow oil. H NMR (CDCl ) δ: 7.19 (t, J = 8.0 Hz 1H, Py), 5.64 (d, J = 7.9 Hz, 2H, Py),
3
1
3
1
4
.09 (s, br, 2H, NH), 3.73 (m, 2H, CH), 1.16 (d, J = 6.5 Hz, 12H, CH3). C{ H} NMR (CDCl ) δ: 157.6
3
+
(
Py), 138.9 (Py), 94.4 (Py), 43.0 (CH), 23.1 (CH ). HRMS (ESI): [M+H] , found 194.1650. C H N
3
11 19
3
requires 194.1652.
4.2.8. N,N'-Bis-(3-methylbutyl)-2,6-diaminopyridine (8). Prepared according to general procedure A.
1
Product was obtained as yellow oil. H NMR (DMSO-d ) δ: 6.97 (t, J = 7.8 Hz, 1H, Py), 5.77 (t, J = 5.5
6
Hz, 2H, NH), 5.56 (d, J = 7.9 Hz, 2H, Py), 3.16 (q, 4H, CH ), 1.63 (m, 2H, CH), 1.38 (q, 4H, CH ), 0.87
2
2
1
3
1
(
d, J = 6.6 Hz, 12H, CH3). C{ H} NMR (DMSO-d ) δ: 158.1 (Py), 137.3 (Py), 93.7 (Py), 38.9 (CH ),
6 2
+
3
8.5 (CH ), 25.4 (CH), 22.5 (CH ). HRMS (ESI): [M+H] , found 250.2278. C H N requires 250.2278.
2 3 15 27 3
4.2.9. N,N'-Dioctyl-2,6-diaminopyridine (9). Prepared according to general procedure A. Product was
1
obtained as yellow oil. H NMR (DMSO-d ) δ: 6.95 (t, J= 7.9 Hz, 1H, Py), 5.80 (t, J = 5.2 Hz, 2H, NH),
6
5.52 (d, J = 7.7 Hz, 2H, Py), 3.12 (q, 4H, CH ), 1.45 (quint, 4H, CH ), 1.24 (m, 20H, CH ), 0.85 (t, J =
2 2 2
1
3
1
6
.3 Hz, 6H, CH3). C{ H} NMR (DMSO-d ) δ: 158.1 (Py), 137.3 (Py), 93.7 (Py), 40.8 (CH ), 31.3
6
2

9
ACCEPTED MANUSCRIPT
+
(
CH ), 29.4 (CH), 28.9 (CH), 28.8 (CH), 26.7 (CH), 22.1 (CH), 13.9 (CH ). HRMS (ESI): [M+H] , found
2
3
3
34.3221. C H N requires 334.3217.
2
1
39
3
4.2.10. N,N'-Dicyclohexyl-2,6-diaminopyridine (10). Prepared according to general procedure A.
1
Product was obtained as yellow oil. H NMR (CDCl ) δ: 7.20 (t, J = 8.1 Hz, 1H, Py), 5.66 (d, J = 8.0
3
Hz, 2H, Py), 4.16 (d, J = 8.2 Hz, 2H, NH), 3.42 (quint, 2H, CH), 2.05 (m, 4H, CH ), 1.76 (m, 6H, CH ),
2
2
1
3
1
1
.24 (m, 10H, CH2). C{ H} NMR (CDCl ) δ: 157.7 (Py), 139.1 (ArH), 94.3 (Py), 50.4 (CH), 33.6 (CH ),
3 2
+
2
6.0 (CH ), 25.1 (CH ). HRMS (ESI): [M+H] , found 274.2274. C H N requires 274.2278.
2
2
17 27
3
4.2.11. N,N'-Bis-(S-1-phenylethyl)-2,6-diaminopyridine (11). Prepared according to general procedure
1
A with 4.2 equivs of amine. Product was obtained as colorless oil. H NMR (DMSO-d ) δ: 7.38-7.12
6
(m, 10H, Ph), 6.92 (t, J = 7.3 Hz, 1H, Py), 6.33 (d, J = 7.9 Hz, 2H, NH), 5.56 (d, J = 7.9 Hz, 2H, Ph),
1
3
1
4
.87 (quint, 2H, CH), 1.27 (d, J = 6.8 Hz, 6H, CH3). C{ H} NMR (DMSO-d ) δ: 157.0 (Py), 146.9 (Ph),
6
+
1
37.3 (Py), 128.0 (Ph), 126.0 (Ph), 126.0 (Ph), 94.8 (Py), 49.6 (CH), 23.6 (CH ). HRMS (ESI): [M+H] ,
3
found 318.1956. C H N requires 318.1965.
2
1
23
3
4.2.12. N,N'-Bis-((R)-1-phenylethyl)-2,6-diaminopyridine (12). Prepared according to general
1
procedure A with 4.2 equivs of amine. Product was obtained as colorless oil. H NMR (DMSO-d ) δ:
6
7.38-7.13 (m, 10H, Ph), 6.91 (t, J = 7.3 Hz, 1H, Py), 6.33 (d, J = 7.9 Hz, 2H, NH), 5.57 (d, J = 7.9 Hz,
1
3
1
2
H, Py), 4.83 (m, 2H, CH), 1.27 (d, J = 6.8 Hz, 6H, CH3). C{ H} NMR (DMSO-d ) δ: 157.0 (Py), 146.9
6
(
q, Ph), 137.3 (Py), 128.0 (Ph), 126.0 (Ph), 126.0 (Ph), 94.8 (Py), 49.6 (CH), 23.6 (CH ). HRMS (ESI):
3
+
[
M+H] , found 318.1956. C H N requires 318.1965.
2
1
23
3
4.2.13. N,N'-Diphenethylpyridine-2,6-diamine (13). Prepared according to general procedure A with
1
4
.2 equivs of amine. Product was obtained as white solid. Mp: 90-91 °C . H NMR (DMSO-d ) δ: 7.22
6
(m, 10H, ArH), 7.03 (t, J = 8.0 Hz, 1H, ArH), 6.06 (t, J = 5.0 Hz, 2H, NH), 5.62 (d, J = 7.8 Hz, 2H, ArH),
1
3
1
3
.38 (q, 4H, CH ), 2.82 (t, J= 7.3 Hz, 4H, CH ). C{ H} NMR (DMSO-d ) δ: 157.9 (Py), 140.1 (Ph),
2 2 6
1
37.6 (Py), 128.6 (Ph), 128.2 (Ph), 125.8 (Ph), 94.3 (Py), 42.8 (CH ), 35.7 (CH ). HRMS (ESI):
2
2
+
[
M+H] , found 318.1957. C H N requires 318.1965.
21 23 3
4.2.14. N,N'-Diphenyl-pyridine-2,6-diamine (14). Prepared according to general procedure A with
1
Pd(PPh ) (10 mg). Product was obtained as fawn crystals. Mp: 102-103 °C . H NMR (DMSO-d ) δ:
3
4
6
8.78 (s, 2H, NH), 7.59 (d, 4H, Ph), 7.36 (t, J = 8.2 Hz, 1H, Py), 7.22 (m, 4H, Ph), 6.87 (t, 2H, Ph), 6.22
1
3
1
(
d, 2H, Py). C{ H} NMR (DMSO-d ) δ: 154.4 (Py), 141.7 (Ph), 138.4 (Py), 128.4 (Ph), 120.2 (Ph),
6
+
19,20
1
18.6 (Ph), 99.7 (Py). HRMS (ESI): [M+H] , found 262.1327. C H N requires 262.1339.
17 15 3
4.2.15. N,N'-Bis-(2,6-dimethylphenyl)-pyridine-2,6-diamine (15). Prepared according to general
procedure A with Pd(PPh ) (10 mg). Product was obtained as fawn crystals. crystals. Mp: 183-
3
4
1
1
85 °C . H NMR (DMSO-d ) δ: 7.44 (s, 2H, NH), 7.08-7.03 (m, 7H, Ph, Py), 5.35 (d, J = 7.9 Hz, 2H,
6
1
3
1
Py), 2.15 (s, 12H, CH3). C{ H} NMR (DMSO-d ) δ: 157.0 (Py), 138.5 (Py), 137.9 (Ph), 136.0 (Ph),
6
+
1
27.9 (Ph), 125.4 (Ph), 94.3 (Py), 18.3 (CH ). HRMS (ESI): [M+H] , found 318.1955. C H N
3
21 23
3
2
0
requires 318.1965.

1
0
ACCEPTED MANUSCRIPT
4.2.16. Allyl-(6-bromopyridine-2-yl)-amine (16). Prepared according to general procedure A. Product
1
was obtained as beige crystals. Mp: < 30 °C. H NMR (DMSO-d ) δ: 7.27 (t, J= 7.45 Hz, 1H, Py), 7.10
6
(
t, br, 1H, NH), 6.62 (d, J = 7.2 Hz, 1H, Py), 6.42 (d, J= 7.8 Hz, 1H, Py), 5.97-5.78 (m, 1H, CH=CH2),
1
3
1
5
.23-5.03 (m, 2H, CH=CH ), 3.85-3.79 (m, 2H, CH ). C{ H} NMR (DMSO-d ) δ: 158.9 (Py), 139.4
2 2 6
+
(
Py), 139.4 (Py), 135.4 (CH=CH ), 115.2 (CH=CH ), 43.0 (CH ). HRMS (ESI): [M+H] , found
2
2
2
2
7
2
13.0012. C H N Br requires 213.0022.
8
9
2
4.2.17. Benzyl-(6-bromopyridine-2-yl)-methyl-amine (17). Prepared according to general procedure
1
with 2.2 equivs. of amine. Product was obtained as beige crystals. Mp: 62.5-63.5 °C . H NMR (DMSO-
d ) δ: 7.27 (m, 6H, ArH), 6.74 (d, J = 7.4 Hz, 1H, ArH), 6.61 (d, J = 8.5 Hz, 1H, ArH), 4.71 (s, 2H, CH ),
6
2
1
3
1
3
.00 (s, 3H, CH3). C{ H} NMR (DMSO-d ) δ: 158.4 (Py), 140.1 (Py), 139.2 (Py), 138.1 (Ph), 128.5
6
+
(
Ph), 127.0 (Ph), 126.9 (Ph), 114.2 (Py), 104.5 (Py), 52.6 (CH ), 36.0 (CH ). HRMS (ESI): [M+H] ,
2
2
2
8
found 277.0330. C H N Br requires 277.0335.
1
3
13
2
4.2.18. N,N,N',N'-Tetramethylpyridine-2,6-diamine (18). Prepared according to general procedure B.
1
Product was obtained as colorless crystals. Mp: 32-33 °C . H NMR (DMSO-d ) δ: 7.23 (t, J = 8.0 Hz,
6
1
3
1
1
H, Py), 5.83 (d, J = 8.2 Hz, 2H, Py), 2.94 (s, 12H, CH3). C{ H} NMR (DMSO-d ) δ: 157.9 (Py), 138.4
6
+
29
(
Py), 92.9 (Py), 37.3 (CH ). HRMS (ESI): [M+H] , found 138.1035. C H N requires 138.1026.
3 7 11 3
4.2.19. 2,6-Di-piperidine-1-yl-pyridine (19). Prepared according to general procedure A. Product was
1
obtained as colorless oil. H NMR (DMSO-d ) δ: 7.22 (t, J = 8.2 Hz, 1H, Py), 5.95 (d, J = 8.2 Hz, 2H,
6
1
3
1
Py), 3.40 (s, 8H, CH ), 1.52 (s, 12H; CH ). C{ H} NMR (DMSO-d ) δ: 157.8 (Py), 138.7 (Py), 94.7
2
2
6
+
(
Py), 45.5 (CH ), 25.0 (CH ), 24.4 (CH ). HRMS (ESI): [M+H] , found 246.1958. C H N requires
2 2 2 15 23 3
3
0
246.1965.
4.2.20. N-Methyl-2,6-diaminopyridine (20). Prepared according to general procedure A. Product was
1
obtained as colorless crystals. Mp: 92-93 °C. H NMR (DMSO-d ) δ: 7.02 (t, J = 7.7 Hz, 1H, Py), 5.79
6
1
3
1
(
pd, 1H), 5.57 (t, J = 8.4 2H), 5.33 (s, 2H), 2.65 (d, J = 4.8 Hz, 3H, CH3). C{ H} NMR (DMSO-d ) δ:
6
+
1
58.9 (Py), 158.6 (Py), 137.9 (Py), 94.6 (Py), 93.8 (Py), 28.1 (CH ). HRMS (ESI): [M+H] , found
3
1
24.0875. C H N requires 124.0869.
6
9
3
4.2.21. N-Isopropylpyridine-2,6-diamine (21). Prepared according to general procedure A. Product
1
was obtained as yellow oil. H NMR (DMSO-d ) δ: 6.98 (t, J = 7.7 Hz, 1H, Py), 5.58-5.54 (m, 3H, Py,
6
1
3
1
NH), 5.27 (s, 2H, NH ), 3.83 (m, 1H, CH), 1.07 (d, J = 6.3 Hz, 6H, CH ). C{ H} NMR (DMSO-d ) δ:
2
3
6
+
1
58.6 (Py), 157.6 (Py), 137.8 (Py), 94.9 (Py), 94.3 (Py), 41.3 (CH), 22.8 (CH ). HRMS (ESI): [M+H] ,
3
found 152.1183. C H N requires 152.1182.
8
13
3
4.2.22. N-(piperidin-1-yl)-pyridine-2,6-diamine (22). Prepared according to general procedure A.
1
Product was obtained as colorless oil. H NMR (DMSO-d ) δ: 7.11 (t, J = 7.9 Hz, 1H, Py), 5.84 (d, J =
6
8
.2 Hz, 1H, Py), 5.70 (d, J = 7.9 Hz, 1H, Py), 5.42 (s, 2H, NH ), 3.39-3.34 (m, 4H, CH ), 1.51 (s, 6H,
2
2
1
3
1
CH2). C{ H} NMR (DMSO-d ) δ: 158.4 (Py), 158.2 (Py), 138.4 (Py), 96.0 (Py), 93.9 (Py), 45.4 (CH ),
6
2
+
2
5.0 (CH ), 24.4 (CH ). HRMS (ESI): [M+H] , found 178.1338. C H N requires 178.1339.
2 2 10 15 3

1
1
ACCEPTED MANUSCRIPT
4.2.23. N-Benzyl-N,N'-dimethyl-pyridine-2,6-diamine (23). Prepared according to general procedure A.
1
Product was obtained as yellow oil. H NMR (DMSO-d ) δ: 7.28-7.10 (m, 6H, Ph, Py), 5.99 (q, 1H,
6
NH), 5.70 (t, J = 7.4 Hz, 2H, Py), 4.73 (s, 2H, CH ), 2.91 (s, 3H, CH ), 2.69 (d, J = 4.9 Hz, 3H, CH ).
2
3
3
1
3
1
C{ H} NMR (DMSO-d ) δ: 158.3 (Py), 157.5 (Py), 139.7 (Ph), 138.1 (Py), 128.2 (Ph), 127.1 (Ph),
6
+
1
26.5 (Ph), 94.5 (Py), 92.0 (Py), 51.9 (CH ), 35.6 (CH ), 27.9 (CH ). HRMS (ESI): [M+H] , found
2
3
3
2
28.1485. C H N requires 228.1495.
1
4
17
3
4.2.24. Benzyl-methyl-(6-piperidine-1-yl-pyridin-2-yl)-amine (24). Prepared according to general
1
procedure A. Product was obtained as yellow oil. H NMR (DMSO-d ) δ: 7.31-7.18 (m, 6H, Ph, Py),
6
5
2
1
.97 (d, J = 7.3 Hz, 2H, Py), 5.83 (d, J = 7.3 Hz, 2H, Py), 4.70 (s, 2H, CH ), 3.42-3.39 (m, 4H, CH ),
2
2
1
3
1
.93 (s, 3H, CH ), 1.50 (s, 6H, CH ). C{ H} NMR (DMSO-d ) δ: 158.3 (Py), 157.5 (Py), 139.7 (Ph),
3
2
6
38.1 (Py), 128.2 (Ph), 127.1 (Ph), 126.5 (Ph), 94.5 (Py), 92.0 (Py), 51.9 (CH ), 35.6 (CH ), 27.9
2
3
+
(
CH ). HRMS (ESI): [M+H] , found 282.1954. C H N requires 282.1965.
3 18 23 3
4.2.25. 2-Bromo-N’6’-(piperidine-1-yl)-pyridine-3,6-diamine (25). Prepared according to general
1
procedure A. Product was obtained as colorless oil. H NMR (DMSO-d ) δ: 5.84 (d, J = 8.2 Hz, 1H,
6
1
3
1
Py), 5.70 (d, J = 7.9 Hz, 1H, Py), 5.42 (s, 2H, NH ), 3.39-3.34 (m, 4H, CH ), 1.51 (s, 6H, CH ). C{ H}
2
2
2
NMR (DMSO-d ) δ: 158.4 (Py), 158.2 (Py), 138.43 (Py), 96.0 (Py), 93.9 (Py), 45.4 (CH ), 25.0 (CH ),
6
2
2
+
2
4.4 (CH ). HRMS (ESI): [M-H] , found 254.0285. C H BrN requires 254.0287.
2 10 14 3
4.2.26. N-(2,6-Bis-methylaminopyridine-3-yl)-acetamide (26). Prepared according to general
1
procedure A. Product was obtained as pink solid. H NMR (DMSO-d ) δ: 7.52 (d, J = 8.2 Hz, 1H, Py),
6
6
.41 (br, 1H, NH), 6.28 (d, J = 8.2 Hz, 1H, Py), 3.58 (s, 3H, CH ), 2.80 (s, 3H, CH ), 2.42 (s, 3H, CH ).
3 3 3
1
3
1
C{ H} NMR (DMSO-d ) δ: 156.2, 147.4, 127.1, 125.1, 103.3, 82.1, 28.2, 27.6, 13.5. HRMS (ESI):
6
+
[
M+H] , found fragment without – H O 177.1133. C H N O requires 194.1168.
2
9
14
4
4.2.27. 3-Nitropyridine-2,6-diamine (27). Prepared according to general procedure with an addition of
DMF (2 mL). The product was diluted with water, filtrated and recrystallized and obtained as yellow
1
solid. Mp: 227-228 °C. H NMR (DMSO-d ) δ: 7.97(d, 1H, J = 9.2 Hz, Py), 7.64 (s, br, 2H, NH ), 7.25
6
2
1
3
1
(
(
s, 2H, NH ), 5.92 (d, J = 9.2 Hz). C{ H} NMR (DMSO-d ) δ: 162.5 (Py), 155.9 (Py), 135.3 (Py), 117.7
2 6
+
31
Py) 101.6 (Py). HRMS (ESI): [M+H] , found 155.0562. C H N O requires 155.0564.
5
6
4
2
4.2.28. 2,6-Diaminopyridine-3,5-dicarbonitrile (28). Prepared according to general procedure with 3
equivs of concentrated NH and iPrOH (7 mL). The product was filtrated and washed with iPrOH and
3
1
Et O and obtained an off-white solid. Mp: > 265 °C . H NMR (DMSO-d ) δ: 8.01 (s, 1H, Py), 7.19 (s,
2
6
1
3
1
4
H, NH2). C{ H} NMR (DMSO-d ) δ: 160.7 (q, Py), 148.1 (Py), 116.8 (Py), 78.7 (CH ). HRMS (ESI):
6
3
+
30
[
M+H] , found 160.0619. C H N requires 160.0618.
7 5 5
4.2.29. 2-Amino-6-tert-butylamino-pyridine-3,5-dicarbonitrile (29). Prepared according to general
procedure with 3 equivs of amine and iPrOH (7 mL). The product was filtrated and washed with iPrOH
1
and Et O and obtained an off-white solid. Mp: 154-155 °C . H NMR (DMSO-d ) δ: 8.02 (s, 2H, NH ),
2
6
2
1
3
1
7
.31 (s, 1H, NH), 5.98 (s, 1H, Py), 1.37 (s, 6H, CH ), 1.21 (s, 3H, CH ). C{ H} NMR (DMSO-d ) δ:
3 3 6
1
60.5 (Py), 158.9 (Py), 148.1 (Py), 117.4 (2CN), 80.9 (Py), 78.1 (Py), 52.9 (C(CH ) ), 29.0 (CH ), 27.6
3
3
3
+
(
CH ). HRMS (ESI): [M+Na] , found 238.1064. C H N requires 238.1063.
3 11 13 5

1
2
ACCEPTED MANUSCRIPT
4.2.30. 2-Amino-6-benzylaminopyridine-3,5-dicarbonitrile (30). Prepared according to general
procedure with 3 equivs of concentrated NH and iPrOH (7 mL). The product was filtrated and washed
3
1
with iPrOH and Et O and obtained as an off-white solid. Mp: 260.5-262 °C . H NMR (DMSO-d ) δ:
2
6
1
3
1
8
.00 (s, 2H, NH ), 7.24 (m, 7H, NH, ArH), 4.50 (d, 2H, CH ). C{ H} NMR (DMSO-d ) δ: 161.1 (Ar),
2 2 6
159.1 (Ar), 148.1 (Py), 139.9 (Ph), 128.6 (Ph), 128.1 (Ph), 127.2 (Ph), 117.3 (CN), 117.2 (CN), 79.8
+
(
Py), 78.6 (Py), 44.0 (CH ). HRMS (ESI): [M+H] , found 250.1081. C H N requires 250.1087.
2
14 11
5

1
3
ACCEPTED MANUSCRIPT
Acknowledgments
Financial support by the Austrian Science Fund (FWF) (Project No. P24202-N17) is gratefully
acknowledged.
Supplementary data
1
13
1
H and C{ H} NMR spectra of compounds 1 - 30. Supplementary data associated with this article can
be found at http://xxxxxxxxxxxxxxxxx.
References
1
2
3
4
(a) Montgomary, J. A.; Secrist, J. A. In Comprehensive Heterocyclic Chemistry; Katrizky, A. R.;
Rees, C. W.; Potts, K. T., Eds.; Pergamon: Oxford, 1984; Vol. 5, 607; (b) Katrizky, A. R.; Qiu,
G.; Long, Q.-H.; He, H.-Y.; Steel, P. J. J. Org. Chem. 2000, 65, 9201.
Lin, R.; Lu, Y.; Wetter, S. K.; Connolly, P. J.; Turchi, I. J.; Murray, W. V.; Emanuel, S. L.;
Gruninger, R. H.; Fuentes-Pesquera, A. R.; Adams, M.; Pandey, N.; Moreno-Mazza, S.;
Middleton, S. A.; Jolliffe, L. K. Bioorg. Med. Chem. Lett. 2005, 15, 2221.
(a) Sathyamoorthy, G.; Soong, M. L.; Ross, T. W.; Boyer, J. H. Heteroatom. Chem. 1993, 4,
603; (b) Araki, K.; Mutai, T.; Shigemitsu, Y.; Yamada, M.; Nakajima, T.; Kuroda, S.; Shimao, I. J.
Chem. Soc., Perkin Trans. 2 1996, 613.
Kusakabe, K.-I.; Ide, N.; Daigo, Y.; Itoh, T.; Higashino, K.; Okano, Y.; Tadano, G.; Tachibana,
Y.; Y. Sato, Y.; Inoue, M.; Wada, T.; Iguchi, M.; Kanazawa, T.; Ishioka, Y.; Dohi, K.;
Tagashira,S.; Kido, Y.; Sakamoto, S.; Yasuo, K.; Maeda, M.; Yamamoto, T.; Higaki, M.;
Endoh,T.; Ueda, K.; Shiota, T.; Murai, H.; Nakamura, Y. ACS Med. Chem. Lett. 2012, 3, 560.
Lechat, P.; Tesleff, S.; Bownan, W. C. Aminopyridines and Similarly Acting Drugs; Pergamon:
Oxford, 1982.
5
6
Lawrence, S. A. in Amines: Synthesis, Properties and Applications, Cambridge University,
Cambridge, 2004.
7
8
9
1
Bolliger, J. L.; Frech, L.; Christian, M. Tetrahedron 2009, 65, 1180.
Salvatore, R. N.; Yoon, C. H.; Jung, K. W. Tetrahedron 2001, 57, 7785.
Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles; Wiley-VCH: Weinheim, 2003; 269.
(a) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901; (b) Paul, F.; Patt, J.;
Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969.
0
11
(a) Marcoux, J.-F.; Wagaw, S.; Buchwald, S. L. J. Org. Chem. 1997, 62, 1568; (b) Nishiyama,
M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998, 39, 617; (c) Jaime-Figueroa, S.; Liu, Y.;
Muchowski, J. M.; Putman, D. G. Tetrahedron Lett. 1998, 39, 1313; (d) Marion, N.; Ecarnot, E.
C.; Navarro, O.; Amoroso, D.; Bell, A.; Nolan, S. P. J. Org. Chem. 2006, 71, 3816; (e) Lorimer,
A. V.; O’Connor, P. D.; Brimble, M. A. Synthesis 2008, 2764.
12
Koley, M.; Schnürch, M.; Mihovilovic, M. D. Tetrahedron, 2011, 67, 4169.

1
4
ACCEPTED MANUSCRIPT
13
14
15
16
Withbroe, G. J.; Singer, R. A.; Sieser, J. E. Org. Process Res. Dev. 2008, 12, 480.
Basu, B.; Jha, S.; Mridha, N. K.; Bhuiyan, Md. M. H. Tetrahedron Letters 2002, 43, 7967.
Blank, B.; Michlik, S.; Kempe, R. Chem. Eur. J. 2009, 15, 3790.
(a) Benito-Garagorri, D.; Becker, E.; Wiedermann, J.; Lackner, W.; Pollak, M.; Mereiter, K.;
Kisala, J.; Kirchner, K. Organometallics 2006, 25, 1900. (b) Glatz, M.; Bichler, B.; Mastalir, M.;
Stöger, B.; Mereiter, K.; Weil, M.; Pittenauer, E.; Allmaier, G.; Veiros, L. F.; Kirchner, K. Dalton
Trans. 2015, 44, 281. (c) Glatz, M.; Holzhacker, C.; Bichler, B.; Mastalir, M.; Stöger, B.;
Mereiter, K.; Weil, M., Veiros, L. F.; Mösch-Zanetti, N. C.; Kirchner, K. Eur. J. Inorg. Chem.
2015, submitted for publication.
1
7
8
(a) Schirmer, W.; Flörke, U.; Haupt, H.-J. Z. Anorg. Allg. Chem. 1987, 545, 83. (b) Schirmer, W.;
Flörke, U.; Haupt, H.-J. Z. Anorg. Allg. Chem. 1989, 574, 239.
1
(a) Okamoto, I.; Terashima, M.; Masu, H.; Nabeta, M.; Ono, K.; Morita, N.; Katagiri, K.;
Azumaya, I.; Tamura, O. Tetrahedron 2011, 67, 8536. (b) Cotton, A. F.; Chao, H.; Murillo, C.
A.; Wang, Q. Dalton Trans., 2006, 5416.
1
2
2
9
0
1
(a) Wagaw, S.; Buchwald, S. L. J. Org. Chem. 1996, 61, 7240. (b) Cotton, F. A.; Daniels, L. M.;
Lei, P.; Murillo, C. A.; Wang, X. Inorg. Chem. 2001, 40, 2778.
Rad’kov, V.; Dorcet, V.; Carpentier, J.-F.; Trifonov, A.; Kirillov, E. Organometallics 2013, 32,
1517.
(a) Hammond, P. R.; Fletcher, A. N.; Bliss, D. E.; Henry, R. A.; Atkins, R. L.; Moore, D. W. App.
Phys. 1976, 9, 67. (b) Bolliger, J. L.; Frech, Christian M. Tetrahedron 2009, 65, 1180.
Madjumar, K. C.; Mondal, S. Tetrahedron Lett. 2007, 48, 6951.
2
2
3
2
Graffner-Nordberg, M.; Kolmodin, K.; Åqvist, J.; Queener, S. F; Hallberg , A. J. Med. Chem.
2001, 44, 2391.
24
25
26
27
28
29
Louërat, F.; Gros, P. C.; Fort, Y. Synlett 2006, 1379.
Gallego, D.; Inoue, S.; Blom, B.; Driess, M. Organometallics 2014, 33, 6885.
Faust, A.; Wolff, O.; Waldvogel, S. R. Synthesis 2009, 155.
Fa, S.-X.; Wang, L.-X.; Wang, D.-X.; Zhao, L.; Wang, M.-X. J. Org. Chem. 2014, 79, 3559.
Bolliger, J. L.; Oberholzer, M.; Frech, C. M. Adv. Synth. Catal. 2011, 353, 945.
Samadi, D. S.; Chioua, M.; do Carmo Carreiras, M.; Marco-Contelles, J. Synth. Commun. 2011,
41, 2859.
3
0
1
Prabhu, R. N.; Ramesh, R. Tetrahedron Lett. 2013, 54, 1120.
3
Hollins, R. A.; Merwin, L. H.; Nissan, R. A.; Wilson, W. S.; Gilardi, R. J. Heterocyclic Chem.
1996, 33, 895.

ACCEPTED MANUSCRIPT
Table 1. Synthesis of N-substituted and N,N’ disubstituted amino pyridines
Entry Reactant Product
t
[
T
[ °C ]
Yield
[%]
h]
1
2
3
4
5
6
7
8
9
1
1
I
2
4
4
2
2
3
5
4
4
5
4
180
180
180
180
180
150
180
200
200
200
210
94
82
78
93
90
83
63
75
73
61
85
N
N
Cl
H
I
N
N
Cl
H
N
N
I
N
N
Cl
Cl
II
II
II
II
II
II
II
II
N
N
N
H
H
N
N
N
H
H
N
N
Br
H
N
N
N
H
H
N
H
N
N
H
C H
C H
8
17
8
17
N
H
N
N
H
0
1
N
N
N
H
H
N
N
N
H
H

ACCEPTED MANUSCRIPT
1
2
3
II
II
4
3
210
210
84
88
N
N
N
H
H
1
N
N
N
H
H
1
4
5
II
II
6
6
225
225
43
19
N
H
N
N
H
1
N
H
N
N
H
16
17
18
19
20
21
22
23
II
3
160
140
180
190
160
150
150
160
82
92
78
78
83
62
95
83
N
H
N
Br
N
N
Br
II
30
4
II
N
N
N
II
4
N
N
N
III
III
III
17
5
H N
N
N
2
H
8
H N
N
N
N
2
H
5
H N
N
2
5
N
H
N
N

ACCEPTED MANUSCRIPT
24
25
26
27
28
29
30
17
IV
5
150
160
165
135
130
80
96
78
75
93
97
69
72
N
N
N
N
NH2
Br
4
N
O
NH
V
4
N
N
N
H
H
NO2
NH2
VI
3
H N
N
2
NC
CN
VII
VII
VII
1.5
1
H N
N
NH2
2
NC
CN
H N
N
N
H
2
NC
CN
1
80
H N
N
N
H
2

ACCEPTED MANUSCRIPT
A practical synthesis of substituted 2,6-diaminopyridines via microwave-assisted
copper-catalyzed amination of halopyridines
Matthias Mastalir, Egon E. Rosenberg, Karl Kirchner*
Supporting Information

ACCEPTED MANUSCRIPT
2
0130602
7
1
\\Srv10\nmr200 mastalir
MeNH2ClP in DMSO
H C
3
HN
N
Cl
8
6
4
2
[ppm]

ACCEPTED MANUSCRIPT
2
0130602
6
1
\\Srv10\nmr200 mastalir
MeNH2ClP in DMSO
2
00
150
100
50
[ppm]

ACCEPTED MANUSCRIPT
2
0130703
7
1
\\Srv10\nmr200 mastalir
CliPrNHP in DMSO
H C
3
H C
HN
N
Cl
3
8
6
4
2
[ppm]

ACCEPTED MANUSCRIPT
2
0130703
8
1
\\Srv10\nmr200 mastalir
CliPrNHP in DMSO
200
150
100
50
[ppm]

ACCEPTED MANUSCRIPT
2
0130610
3
1
\\Srv10\nmr200 mastalir
ClP-Piperazin in DMSO
8
6
4
2
[ppm]

ACCEPTED MANUSCRIPT
2
0130610
4
1
\\Srv10\nmr200 mastalir
ClP-Piperazin in DMSO
2
00
150
100
50
[ppm]

ACCEPTED MANUSCRIPT
MMTU050
1
1
"H:\Dokumente und Einstellungen\Matthias\..." mastalir
MeNH2Pyr aus MW durch Br2Pyr u MeNH2 DMSO
H C
3
CH
3
HN
N
HN
8
6
4
2
0 [ppm]

ACCEPTED MANUSCRIPT
MMTU050
3
1
H:\Bruker\TOPSPIN Mastalir
MeNH2Pyr aus MW durch Br2Pyr u MeNH2 DMSO
2
00
150
100
50
[ppm]

ACCEPTED MANUSCRIPT
Handversuche 50
Et2DAP in DMSO
1
H:\Bruker\TOPSPIN Mastalir
H C
HN
N
HN
CH
3
3
8
6
4
2
[ppm]

ACCEPTED MANUSCRIPT
Handversuche 51
Et2DAP in DMSO
1
H:\Bruker\TOPSPIN Mastalir
2
00
150
100
50
[ppm]