Abstract
A library of 5-aryl-4-methylpyrimidines, phenyl ring-substituted
derivatives of 4-benzylpyrimidines, 2,6-benzylpyridines, and 2,6-dibenzyl-4-methylpyridines
were prepared. The synthesis of 5-aryl-4-methylpyrimidines was accomplished
by Suzuki-Miyaura cross-coupling reaction between
arylboronic acids and 5-bromo-4-methylpyrimidine. The 4-benzylpyrimidines
and 2,6-benzylpyridines were synthesized by treatment of 4-bromopyrimidine
and 2,6-dibromopyridine derivatives with ring-substituted benzylzinc
reagents.
Key words
cross-coupling reaction - amphetamine analogues - Leuckart
synthesis - drugs - heterocycles
References
<A NAME="RT60411SS-1A">1a</A>
Joule JA.
Mills K.
Smith GF. In Heterocyclic Chemistry
Chapman & Hall;
London:
1995.
<A NAME="RT60411SS-1B">1b</A>
Itami K.
Yamazaki D.
Yoshida J.-i.
J.
Am. Chem. Soc.
2004,
126:
15396
<A NAME="RT60411SS-1C">1c</A>
Baldwin BC.
Corran AJ.
Robson M.
J. Pestic. Sci.
1995,
44:
81
<A NAME="RT60411SS-1D">1d</A>
Wong K.-T.
Hung TS.
Wu ChCh.
Lee G.-H.
Peng S.-M.
Chou Ch.-S.
Su YO.
Org.
Lett.
2002,
4:
513
<A NAME="RT60411SS-2A">2a</A>
van der Ark AM.
Sinnema A.
Theeuwen ABE.
van der Torn JM.
Verweij AMA.
Pharm.
Weekbl.
1978,
113:
41
<A NAME="RT60411SS-2B">2b</A>
van der Ark AM.
Sinnema A.
van der Torn JM.
Verweij AMA.
Pharm.
Weekbl.
1978,
113:
341
<A NAME="RT60411SS-2C">2c</A>
van der Ark AM.
Verweij AMA.
Sinnema A.
J. Forensic Sci.
1978,
23:
693
<A NAME="RT60411SS-3A">3a</A>
Cloonan SM.
Keating JJ.
Corrigan D.
O’Brien JE.
Kavanagh PV.
Wiliams DC.
Meegan MJ.
Bioorg. Med. Chem.
2010,
18:
4009
<A NAME="RT60411SS-3B">3b</A>
Bohn M.
Bohn G.
Blaschke G.
Int.
J. Leg. Med.
1993,
106:
19
<A NAME="RT60411SS-3C">3c</A>
Błachut D.
Wojtasiewicz K.
Czarnocki Z.
Forensic
Sci. Int.
2005,
152:
157
<A NAME="RT60411SS-4A">4a</A>
Sinnema A.
Verweij AMA.
Bull. Narc.
1981,
33:
37
<A NAME="RT60411SS-4B">4b</A>
Verweij AMA.
Forensic Sci. Rev.
1989,
1:
1
<A NAME="RT60411SS-5">5</A>
Waumans D.
Bruneel N.
Tytgat J.
Forensic
Sci. Int.
2003,
133:
159
<A NAME="RT60411SS-6">6</A>
Błachut D.
Wojtasiewicz K.
Krawczyk K.
Maurin J.
Szawkało J.
Czarnocki Z.
Forensic Sci. Int.
2011, in
press
<A NAME="RT60411SS-7A">7a</A>
Błachut D.
Wojtasiewicz K.
Czarnocki Z.
Forensic Sci. Int.
2002,
127:
45
<A NAME="RT60411SS-7B">7b</A>
Błachut D.
Maurin JK.
Starosta W.
Wojtasiewicz K.
Czarnocki Z.
Z. Naturforsch.,
B
2002,
57:
593
<A NAME="RT60411SS-7C">7c</A>
Błachut D.
Danikiewicz W.
Wojtasiewicz K.
Olejnik M.
Kalinowska I.
Szawkało J.
Czarnocki Z.
Forensic
Sci. Int.
2011,
206:
197
<A NAME="RT60411SS-8A">8a</A>
Dodson RM.
Sayler JK.
J. Org. Chem.
1952,
16:
461
<A NAME="RT60411SS-8B">8b</A>
Muller TJJ.
Braun R.
Ansorge M.
Org. Lett.
2000,
2:
1967
<A NAME="RT60411SS-9A">9a</A>
Koyama T.
Hirota T.
Bashon C.
Satoh Y.
Shinhara Y.
Watanabe Y.
Matsumoto S.
Shinohara Y.
Ohmori S.
Yamato M.
Chem. Pharm.
Bull.
1975,
23:
2158
<A NAME="RT60411SS-9B">9b</A>
Kirkbridge KP.
Ward AD.
Jenkins NF.
Klass G.
Coumbaros JC.
Forensic Sci. Int.
2001,
115:
53
<A NAME="RT60411SS-10">10</A>
Błachut D.
Czarnocki Z.
Wojtasiewicz K.
Synthesis
2006,
2855
<A NAME="RT60411SS-11">11</A>
Schröter S.
Stock Ch.
Bach T.
Tetrahedron
2005,
61:
2245
<A NAME="RT60411SS-12">12</A>
Schomaker JM.
Delia TJ.
J. Org. Chem.
2001,
66:
7125
<A NAME="RT60411SS-13">13</A>
Parry PR.
Wang Ch.
Batsanov AS.
Bryce MR.
Tarbit B.
J.
Org. Chem.
2002,
67:
7541
<A NAME="RT60411SS-14">14</A>
Ceide SC.
Montalban AG.
Tetrahedron Lett.
2006,
47:
4415
<A NAME="RT60411SS-15A">15a</A>
Van der Plas HC.
Rec.
Trav. Chim. Bays-Pas
1965,
84:
1101
<A NAME="RT60411SS-15B">15b</A>
Yamanaka H.
Sakamoto T.
Nishimura S.
Sagi M.
Chem. Pharm. Bull.
1987,
35:
3119
<A NAME="RT60411SS-16">16</A>
The outcome of the reactions was controlled
by GC-MS. The advantage of the GC-MS method is that it can be applied
to complicated mixtures of compounds, providing useful information
of their composition and the products ratio. Obviously, the differences
in the mass spectra of closely related isomers cannot be spectacular
but due to a similar fragmentation routes, the total ion current
should be similar for substrate, final products and by-products
formed. Consequently, the intensities (peak area) of the peaks in chromatograms
are a good measure for the proportion of substances in the mixture.
In our case, the conversion was calculated by comparison of the
peak area of remaining substrate with a sum of peak areas of the
final product and by-products. The yield of a particular component
was calculated by comparing of a peak area of the product with a sum
of peak areas recorded for remaining products and substrate (if
present).
<A NAME="RT60411SS-17">17</A>
Wolfe JP.
Buchwald SL.
Angew. Chem. Int.
Ed.
1999,
38:
2413
<A NAME="RT60411SS-18">18</A>
Wiley
Registry 8th/NIST 2005 Mass Spectral Library
Wiley;
New
Jersey:
2006.
<A NAME="RT60411SS-19A">19a</A>
King LA.
Poortman van der Meer AJ.
Sci. Justice
2001,
41:
200
<A NAME="RT60411SS-19B">19b</A>
Westphal F.
Rösner P.
Junge Th.
Forensic.
Sci. Int.
2010,
194:
53
<A NAME="RT60411SS-20">20</A>
Abbotto A.
Alanzo V.
Bradamante S.
Pagani GA.
J. Chem.
Soc., Perkin Trans. 2
1991,
481
<A NAME="RT60411SS-21">21</A>
Luke R. W. A. inventors; US
Patent US2006/0069109 A1.
<A NAME="RT60411SS-22">22</A>
Metzger A.
Schade MA.
Knochel P.
Org.
Lett.
2008,
10:
1107
<A NAME="RT60411SS-23">23</A>
Unpublished results.
<A NAME="RT60411SS-24">24</A>
Minato A.
Tamao K.
Hayashi T.
Suzuki K.
Kumada M.
Tetrahedron
Lett.
1980,
21:
845
<A NAME="RT60411SS-25">25</A>
Berstein J.
Stearns B.
Shaw E.
Lott WA.
J. Am. Chem. Soc.
1947,
69:
1151