PAPER
w-Functionalized 3-Alkynylpyrazolo[1,5-a]pyrimidines by Sonogashira Coupling
135
for 16 h. It was filtered through a pad of Celite, washed with EtOAc.
The solvent was evaporated and the residue was purified by flash
chromatography on standard neutral Al2O3, eluting with EtOAc–
MeOH (1:0 → 10:1) to give the product 2a,2b.
(12) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467. (b) Sonogashira, K. J. Organomet.
Chem. 2002, 653, 46. (c) Alami, M.; Ferri, F.; Linstrumelle,
G. Tetrahedron Lett. 1993, 34, 6403. (d) Negishi, E.;
Anastasia, L. Chem. Rev. 2003, 103, 1979. (e) Sakomoto,
T.; Shiga, F.; Yasuhara, A.; Yamanaka, H. Synthesis 1992,
746.
N,N-Dimethyl-N-[3-(2-methyl-5,7-diphenylpyrazolo[1,5-a]py-
rimidin-3-yl)propyl]amine (2a)
Yield: 37%; yellow solid; mp 72–74 °C.
(13) (a) Li, J. J.; Gribble, G. W. Palladium in Heterocyclic
Chemistry; Pergamon Press: Oxford, 2000. (b) Kalinin, V.
N. Synthesis 1991, 413. (c) Edo, K.; Yamanaka, H.;
Sakamoto, T. Heterocycles 1978, 9, 271. (d) Mcguigan, C.;
Yarnold, C. J.; Jones, G.; Balzarini, J. J. Med. Chem. 1999,
42, 4479. (e) Turner, S. C.; Esbenshade, T. A.; Bennani, Y.
L.; Hancock, A. A. Bioorg. Med. Chem. Lett. 2003, 12,
1683. (f) Arnautu, A.; Collot, V.; Ros, J. C.; Witulski, B.
Tetrahedron Lett. 2002, 43, 2695. (g) Kim, J. T.;
Gevorgyan, V. Org. Lett. 2002, 4, 4697. (h) Negishi, E.;
Qian, M. X.; Zeng, F. X.; Anastasia, L.; Babinski, D. Org.
Lett. 2003, 5, 1597.
1H NMR (300 MHz, CDCl3): d = 1.95–2.06 (m, 2 H, CH2), 2.28 (s,
6 H, 2 × CH3), 2.44 (t, J = 7.5 Hz, 2 H, CH2), 2.95 (t, J = 7.9 Hz, 2
H, CH2), 7.31 (s, 1 H, H-6), 7.50–8.05 (m, 10 H, Ph-H), 8.07 (s, 1
H, H-2).
13C NMR (75 MHz, CDCl3): d = 21.0 (CH2), 28.3 (CH2), 45.5
(CH3), 59.4 (CH2), 104.7 [CH(C-6)], 110.8 (C), 127.2 (CH), 128.7
(CH), 128.9 (CH), 129.2 (CH), 130.1 (CH), 130.8 (CH), 131.7 (C),
137.7 (C), 144.5 (CH), 146.5 (C), 147.1 (C), 154.5 (C).
Anal. Calcd for C23H24N4 (356.46): C, 77.50; H, 6.79; N, 15.72.
Found: C, 77.62; H, 6.95; N, 15.48.
(14) (a) Muehldorf, A. V.; Guzman-Perez, A.; Kluge, A. F.
Tetrahedron Lett. 1994, 35, 8755. (b) Tilley, J. W.; Levitan,
P.; Lind, J.; Welton, A. F.; O’Donnell, M. J. Med. Chem.
1987, 30, 185. (c) Clitherow, J. W.; Scopes, D. C.; Skingle,
M.; Jorden, C. C. J. Med. Chem. 1994, 37, 2253.
N,N-Dimethyl-N-[3-(5,7-diphenylpyrazolo[1,5-a]pyrimidin-3-
yl)propyl]amine (2b)
Yield: 40%; yellow solid; mp 93–94 °C.
1H NMR (300 MHz, CDCl3): d = 1.82–1.91 (m, 2 H, CH2), 2.18 (s,
6 H, CH3), 2.32 (t, J = 7.5 Hz, 2 H, CH2), 2.40 (s, 3 H, CH3), 2.81
(t, J = 7.5 Hz, 2 H, CH2), 7.13 (s, 1 H, H-6), 7.40–7.49 (m, 6 H, Ph-
H), 7.99–8.02 (m, 2 H, Ph-H), 8.06–8.09 (m, 2 H, Ph-H).
13C NMR (75 MHz, CDCl3): d = 13.2 (CH3), 20.6 (CH2), 28.3
(CH2), 45.6 (CH3), 59.6 (CH2), 103.8 [CH (C-6)], 108.3 (C), 127.1
(CH), 128.7 (CH), 128.8 (CH), 129.2 (CH), 129.9 (CH), 130.7
(CH), 131.9 (C), 137.9 (C), 145.7 (C), 147.9 (C), 153.6 (C), 154.2
(C).
(d) Lammothe, M.; Pauwels, P. J.; Belliard, K.; Schambel,
P.; Halazy, S. J. Med. Chem. 1997, 40, 3542.
(15) (a) Elsevier, C. J.; Kleijn, H.; Ruitenberg, K.; Vermeer, P. J.
Chem. Soc., Chem. Commun. 1983, 1529. (b) Elsevier, C.
J.; Kleijn, H.; Boersma, J.; Vermeer, P. Organometallics
1986, 5, 716.
(16) Heidenreich, R. G.; Köhler, K.; Krauter, J. K.; Pietsch, J.
Synlett 2002, 1118.
(17) (a) Gala, D.; Jenkins, S. J.; Kugelman, M. Org. Proc. Res.
Dev. 1997, 1, 163. (b) Dyer, U. C.; Shapland, P. D.; Tiffin,
P. D. Tetrahedron Lett. 2002, 42, 1765. (c) McClure, M. S.;
Roschangar, F.; Hodson, S. J.; Millar, A.; Osterhout, M. H.
Synthesis 2001, 1681. (d) Sakurai, H.; Tsukuda, T.; Hirao,
T. J. Org. Chem. 2002, 67, 2721. (e) Tagata, T.; Nishida, M.
J. Org. Chem. 2003, 68, 9412. (f) LeBlond, C. R.; Andrews,
A. T.; Sun, Y. K.; Sowa, J. R. Jr. Org. Lett. 2001, 3, 1555.
(g) Organ, M. G.; Mayer, S. J. Comb. Chem. 2003, 5, 118.
(h) Accadi, A.; Cerichelli, G.; Chiarini, M.; Correa, M.;
Zorzan, D. Eur. J. Org. Chem. 2003, 4080.
Anal. Calcd for C24H26N4 (370.49): C, 77.80; H, 7.07; N, 15.12.
Found: C, 77.92; H, 7.14; N, 15.07.
Acknowledgment
We gratefully acknowledge financial support by Deutsche For-
schungsgemeinschaft, Fonds der Chemischen Industrie and Elbion
AG.
(18) (a) Reardon, P.; Metts, S.; Crittendon, C.; Dangherity, P.;
References
Parson, E. J. Organometallics 1995, 14, 3810.
(b) Hagiwara, H.; Shimizu, Y.; Hoshi, T.; Suzuki, T.
Tetrahedron Lett. 2001, 42, 4349. (c) Xie, X. F.; Lu, J. P.;
Chen, B.; Han, J. J.; She, X. G.; Pan, X. F. Tetrahedron Lett.
2004, 45, 809. (d) Mehnert, C. P.; Weaver, D. W.; Ying, J.
Y. J. Am. Chem. Soc. 1998, 120, 12289. (e) Khan, S. I.;
Grinstaff, M. W. J. Org. Chem. 1999, 64, 1077.
(1) Novinson, T.; Bhooshan, B.; Okabe, T.; Revankar, G. R.;
Wilson, H. R. J. Med. Chem. 1976, 19, 512.
(2) Senga, K.; Novinson, T.; Wilson, H. R. J. Med. Chem. 1981,
24, 610.
(3) Suzuki, M.; Iwasaki, H.; Fujikawa, Y.; Sakashita, M.;
Kitahara, M.; Sakoda, R. Bioorg. Med. Chem. Lett. 2001, 11,
1285.
(4) Almansa, C.; Arriba, A. F.; Cavalcanti, F. L.; Gomez, L. A.;
Miralles, A.; Forn, J. J. Med. Chem. 2001, 44, 350.
(5) Fraley, M. E.; Rubino, R. S.; Hoffman, W. F.; Hambaugh, S.
R.; Thomas, K. A. Bioorg. Med. Chem. Lett. 2002, 12, 3537.
(6) Novinson, T.; Hanson, R.; Dimmitt, M. K.; Simmon, L. N.;
Robins, R. K.; O’Brien, D. E. J. Med. Chem. 1974, 17, 645.
(7) Selleri, S.; Bruni, F.; Costagli, C.; Costanzo, A.; Guerrini,
G.; Ciciani, G.; Costa, B.; Martini, C. Bioorg. Med. Chem.
2001, 9, 2661.
(19) (a) Potts, K. T.; Horwitz, C. P.; Fessak, A.; Keshavarz-K,
M.; Nash, K. E.; Toscano, P. J. J. Am. Chem. Soc. 1993, 115,
10444. (b) Bleicher, L. S.; Cosford, N. D. P. Synlett 1995,
1115. (c) Cosford, N. D. P.; Bleicher, L.; Herbaut, A.;
McCallum, J. S.; Vernier, J. M. J. Med. Chem. 1996, 39,
3235. (d) Bleicher, L. S.; Cosford, N. D. P.; Herbaut, A.;
McCallum, J. S.; McDonald, I. A. J. Org. Chem. 1998, 63,
1109. (e) Novak, Z.; Szabo, A.; Kotschy, A. J. Org. Chem.
2003, 68, 3327. (f) Bates, R. W.; Boonsombat, J. J. Chem.
Soc., Perkin Trans. 1 2001, 654. (g) Lopez-Deber, M. P.;
Castedo, L.; Granja, J. R. Org. Lett. 2001, 3, 2823. (h) Pal,
M.; Subramanian, V.; Yeleswarapu, K. R. Tetrahedron Lett.
2003, 44, 8221.
(8) Kirkpatrick, W. E.; Okabe, T.; Hillyard, I. W.; Robin, R. K.;
Dren, A. T. J. Med. Chem. 1977, 20, 386.
(9) Calderwood, D. J.; Johnson, D. N.; Munschauer, R.;
Rafferty, P. Bioorg. Med. Chem. Lett. 2002, 12, 1683.
(10) Karanik, M.; Pätzel, M.; Liebscher, J. Synthesis 2003, 1201.
(11) Yin, L. X.; Liebscher, J. Synthesis 2004, 2329.
(20) Koradin, C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.;
Knochel, P. Tetrahedron 2003, 59, 1571.
(21) Fairlamb, I. J. S.; Bäuerlein, P. S.; Marrison, L. R.;
Dickinson, J. M. Chem. Commun. 2003, 632.
Synthesis 2005, No. 1, 131–135 © Thieme Stuttgart · New York