RSC Advances
ARTICLE
0 mmol scale synthesis:ꢀ
DOI: 10.1039/C5RA0146
Journal Na1Ame
d
1
Departamento de Bioquímica y Biología Molecular B
eInmunología. Facultad de Química, Regional Campus of
International Excellence “Campus Mare Nostrum”,Universidad
de Murcia, 30071 Murcia, Spain
StepꢀA A solution of precatalyst Id (1 mol%) in dry CH CN (40 ml)
3
was stirred for 5 min at ambient temperature under N .Then,5ꢀIodo
2
2
’ꢀdeoxyuridine (10 mmol) was added and the solution stirred for 5
e
Departamento de Ingeniería Minera, Geológica y Cartográfica.
min at 80 C.Thereafter, Et N (20 mmol) and alkene linker (15 Universidad Politécnica de Cartagena. Área de Química
o
3
Inorgánica, Regional Campus of International Excellence
mmol) were also added with CH CN (20 ml).The resulting solution
3
"
Campus Mare Nostrum", Universidad Politécnica de
o
was then stirred at 80 C for required amount of time. After the
Cartagena, 30203, Cartagena, Spain
resultant residue obtained was purified using column
1
. For a review on Pdꢀcatalysed crossꢀcoupling reactions see: C. C. C.
chromatography in CH Cl :MeOH solvent system (97:3) to afford
2
2
Johanson, M. O. Kitching, T. J. Colacot, V. Snieckus, Angew. Chem. Int.
Ed., 2012, 51, 5062.
the desired product as a white solid (84%, 2.6g).
StepꢀB (E)ꢀ5ꢀ[2ꢀcarbomethoxyvinyl]ꢀ2′ꢀdeoxyuridine
MA
(dU ). 2. Palladium-Catalysed Coupling Reactions: Practical Aspects and
Future Developments. (Ed. A. Molnar,) WileyꢀVCH Verlag, 2013.
(2.6g,8.3 mmol) was dissolved in 1M NaOH (140 ml) and the
3
. a) Metal-Catalyzed Cross-Coupling Reactions, (Eds.: A. de Meijere, F.
H
mixture stirred for 3 hrs,filtered and filtrate adjusted P 2 with 1M
Diederich), WileyꢀVCH, Weinheim, 2004; b) Handbook of
o
HCl. On cooling at 4 C a white precipitate formed. This was filtered Organopalladium Chemistry for Organic Synthesis (Eds.: E. Negishi, A.
de Meijere,), Wiley, New York, 200.
off and washed with cold water (2×10ml) and acetone (2×10ml) and
4
. K. C. Nicolaou, P. C. Bulger, D. Sarlah, Angew. Chem. Int. Ed., 2005,
, 4442.
dried to give a white solid.(90%,2.2g).
44
StepꢀC To
a
solution of (E)ꢀ5ꢀ(2ꢀCarboxyvinyl)ꢀ2’ꢀ 5. A. Suzuki, Angew. Chem., Int. Ed., 2011, 50, 6722.
deoxyuridine (2.2 g, 7.4 mmol) in DMF (12 ml) was added 6. J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508.
K CO (2.22 g, 16 mmol) and the suspension stirred at room 7. a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett., 1975, 16
,
2
3
temperature for 15 min. Then added NBS (1.44 g, 8.0 mmol) 4467.
fractionꢀwise over 30 min at ambient temperature. After 8. a) J. F. Hartwig, Acc. Chem. Res., 1998, 31, 852. b) B. H. Yang, S. L.
completion of reaction, the solvent was removed under vacuo Buchwald, J. Organomet. Chem., 1999, 576, 125.
and the resultant residue obtained was purified using column 9. a) R. F. Heck, J. Am. Chem. Soc., 1968, 90, 5518. b) T. Mizoroki, K.
chromatography in CH Cl :MeOH solvent system(96:8) to Mori, A. Ozaki, Bull. Chem. Soc. Japan, 1971, 44, 581.
2
2
afford the desired product as a white solid.(90%, 2.21 g).
10. (a) G. Sánchez, J. García, M. Martínez, J. Pérez, L. García,; J. L.
Serrano, A. R. Kapdi, Dalton Trans., 2011, 40, 12676. (b) M. D. Santana,
General procedure for Recycling studies for Heck alkenylation R. GarcíaꢀBueno, G. García, G. Sánchez, J. García, M. Naik, S. Pednekar,
A. R. Kapdi, J. Pérez, L. García, E. Pérez, J. L. Serrano, Dalton Trans.,
of pyrimidine nucleosides.
2
012, 41, 3832. (c) J. L. Serrano, J. Pérez, L. García, G. Sánchez, J.
García, K. Tyagi, A. R. Kapdi, RSC Advances, 2012,
1. a) M. K. Lakshman, J. Organomet. Chem., 2002, 653, 234. b) L. A.
Agrofoglio, I. Gillaizeau, Y. Saito, Chem. Rev., 2003, 103, 1875. c) M. K.
Lakshman, Curr. Org. Synth., 2005, , 83.
2. a) V. Vongsutilers, J. R. Daft, K. H. Shaughnessy, P. M. Gannett,
Molecules, 2009, 14, 3339. b) G. Herve, G. Sartori, G. Enderlin, G.
Mackennzie, C. Len, RSC Advances, 2014, , 18558.
3. a) N. J. Greco, Y. Tor, J. Am. Chem. Soc., 2005, 127, 1078. b) P.
2, 12237.
A solution of precatalyst Id (1.0 mol%) in dry CH CN (1.0 mL)
3
1
was stirred for 5 min at ambient temperature under N . Then,
2
nucleoside (0.5 mmol) was added and the solution stirred for 5
o
2
min at 80 C. Thereafter, Et N (1.0 mmol) and alkene linker
3
1
(
0.5 mmol) were also added with CH CN (1.0 mL). The
3
resulting solution was then stirred at 80 °C for required amount
of time. After the completion of reaction, an aliquot of the
reaction mixture was injected in an HPLC to confirm the yield
obtained. On completion of the reaction another batch of
4
1
Wigerinck, L. Kerremans, P. Claes, R. Snoeck, P. Maudgal, E. De Clercq,
P. Herdewijn, J. Med. Chem., 1993, 36, 538. c) E. Mayer, L. Valis, R.
Huber, N. Amann, H. A. Wagenknecht, Synthesis, 2003, 15, 2335.
nucleoside, Et N and alkene linker was added and the reaction
3
continued.
1
4. a) S. GallagherꢀDuval, G. Herve, G. Sartori, G. Enderlin, C. Len, New
J. Chem., 2013, 37, 1989. b) N. Fresneau, M. A. Hiebel, L. A.
Agrofoglio, S. BerteinaꢀRaboin, Molecules, 2012, 17, 14409. c) G.
Sartori, G. Enderlin, G. Herve, C. Len, Synthesis, 2012, 44, 767. d) G.
Sartori, G. Herve, G. Enderlin, C. Len, Synthesis, 2013, 45, 330.
6
.
Notes and References
a
Institute of Chemical Technology, Mumbai, Nathalal road,
Matunga, Mumbaiꢀ400019, India
Rasayan Inc. 2802, Crystal Ridge Road, Encinitas, California,
2024ꢀ6615, United States of America
Departamento de Químic Inorgánica, Regional Campus of
International Excellence “Campus Mare Nostrum” Universidad
de Murcia, 30071 Murcia, Spain
b
1
5. a) E. De Clercq, C. Desgranges, P. Herdewin, I. S. Sim, A. S. Jones,
9
c
M. J. McLean, R. T. Walker, J. Med. Chem., 1986, 29, 213. b) R. F.
Whale, P. L. Cole, R. T. Walker, Nucleosides and Nucleotides, 1991, 10
,
1
615.
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| J. Name., 2012, 00, 1-3
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