LETTER
Synthesis and Chemical Transformations of Dihydrodiquinolinopyrazines
2003
Berthier, L.; Pfeiffer, B.; Renard, P.; Pierre, A.; Caubère, P.;
Guillaumet, G. J. Med. Chem. 2004, 47, 978.
(
(
(
7) Sabol, M. R.; Owen, J. M.; Erickson, W. R. Synth. Commun.
2000, 30, 427.
8) Miura, Y.; Takaku, S.; Nawata, Y.; Hamana, M.
Heterocycles 1991, 32, 1579.
9) Marsais, F.; Godard, A.; Queguiner, G. J. Heterocycl. Chem.
1989, 26, 1589.
(10) Under optimal conditions 1 equiv of bromo derivative
necessitates 2 equiv of complex base (in other words 4 equiv
NaNH and 2 equiv of t-BuONa) and one supplementary
2
equiv of NaNH for the formation of the sodium salt of the
2
bromoamine. Thus, the basic reagent must be prepared by
addition of 2 equiv of t-BuOH to 7 equiv of NaNH .
2
–
1
(
11) Compound 6b: IR (KBr): 1345, 1452 cm . MS: m/z = 397
1
[
M + 1]. H NMR (250 MHz, CDCl ): d = 1.06 (6 H, q,
J = 7.3 Hz, 2 CH ), 1.54–1.58 (4 H, m, 2 CH ), 1.70–1.82 (4
3
3
2
H, m, 2 CH ), 4.12–4.15 (4 H, t, 2 CH N, J = 6.8 Hz), 6.79
2
2
(
2 H, s), 7.15 (2 H, ddd, J = 7.3 Hz, J = 6.9 Hz, J = 1.2 Hz),
.29 (2 H, ddd, J = 1.5 Hz, J = 6.9 Hz, J = 7.3 Hz), 7.40 (2
H, dd, J = 7.3 Hz, J = 1.5 Hz), 7.53 (2 H, dd, J = 7.3 Hz,
7
1
3
J = 1.2 Hz). C NMR (62.5 MHz, CDCl ): d = 13.8 (2 CH ),
3
3
2
1
1
0.6 (2 CH ), 31.5 (2 CH ), 41.3 (2 CH N), 119.1 (2 C),
19.5 (2 CH), 122.4 (2 CH), 126.0 (2 CH), 127.9 (2 CH),
29.7 (2 CH), 130.2 (2 C), 140.6 (2 C), 144.4 (2 C).
Compound 7b: IR (KBr): 1347, 1455 cm . MS: m/z = 397
M + 1]. H NMR (250 MHz, CDCl ): d = 1.06 (6 H, q,
J = 7.2 Hz, 2 CH ), 1.47–1.62 (4 H, m, 2 CH ), 1.74–1.86 (4
2
2
2
Scheme 6 (i) (COOH) (5 equiv), CH Cl then KNO (1 equiv),
–1
2
2
2
2
MeNO2.
1
[
3
3
2
H, m, 2 CH ), 3.61 (2 H, t, J = 7.6 Hz, CH N), 4.49 (2 H, t,
2
2
J = 7.6 Hz, CH N), 6.66 (2 H, s), 7.16 (2 H, ddd, J = 7.1 Hz,
2
References
J = 6.8 Hz, J = 1.1 Hz), 7.32 (2 H, ddd, J = 1.2 Hz, J = 6.8
Hz, J = 7.5 Hz), 7.58 (2 H, dd, J = 7.1 Hz, J = 1.2 Hz), 7.65
(
1) (a) Caubère, P. Acc. Chem. Res. 1974, 7, 301. (b) Caubère,
P. Top. Curr. Chem. 1978, 73, 50. (c) Caubère, P. Rev.
Heteroatom. Chem. 1991, 4, 78. (d) Caubère, P. Chem. Rev.
1
3
(
2 H, dd, J = 7.5 Hz, J = 1.1 Hz). C NMR (62.5 MHz,
CDCl ): d = 13.8 (2 CH ), 20.6 (2 CH ), 32.9 (CH ), 33.5
3
3
2
2
(
CH ), 41.3 (CH N), 42.9 (CH N), 116.6 (2 C), 120.3 (2
1993, 93, 2317. (e) Caubère, P. J. Chin. Chem. Soc. 1998,
2 2 2
CH), 121.4 (2 CH), 123.3 (2 CH), 125.0 (2 CH), 127.8 (2
CH), 128.4 (2 C), 137.6 (2 C), 145.5 (2 C).
45, 451; and references cited in these reviews.
(
2) (a) Carré, M. C.; Youlassani, A.; Caubère, P.; Saint-Aubin-
(
(
12) Marson, C. M.; Giles, P. R. Synthesis Using Vilsmeier
Reagents; C.R.C. Press: Boca Raton, 1994.
13) (a) Gross, H.; Rieche, A.; Mathey, G. Chem. Ber. 1963, 96,
Floch, A.; Blanc, M.; Advenier, C. J. Med. Chem. 1984, 27,
7
92. (b) Jamart-Grégoire, B.; Caubère, P.; Blanc, M.;
Gnassounou, J. P.; Advenier, C. J. Med. Chem. 1989, 32,
15. (c) Aatif, A.; Mouaddib, A.; Carré, M. C.; Jamart-
308. (b) Rieche, A.; Gross, H.; Hoft, E. Org. Synth., Coll.
3
Vol. V 1973, 49.
Grégoire, B.; Geoffroy, P.; Zouaoui, M. A.; Caubère, P.;
Blanc, M.; Gnassounou, J. P.; Advenier, C. Eur. J. Med.
Chem. 1990, 25, 441. (d) Kuehm-Caubère, C.; Caubère, P.;
Jamart-Grégoire, B.; Nègre-Salvayre, A.; Bonnefont-
Rousselot, D.; Bizot-Espiard, J. G.; Pfeiffer, B.; Caignard,
D. H.; Guardiola-Lamaître, B.; Renard, P. J. Med. Chem.
(
(
14) Satya, P.; Mukta, G.; Rajive, G. Synlett 2000, 1115.
–
1
15) Compound 8: IR (KBr): 1433, 1676 cm . MS: m/z = 425 [M
1
+
1]. H NMR (250 MHz, CDCl ): d = 0.74 (t, 3 H, CH ,
3
3
J = 7.2 Hz), 1.03 (t, 3 H, CH , J = 7.2 Hz), 1.20–1.29 (m, 2
3
H, CH ), 1.51–1.59 (m, 2 H, CH ), 1.65–1.82 (m, 4 H, 2
2
2
CH ), 4.24 (t, 2 H, CH N, J = 7.5 Hz), 4.31 (t, 2 H, CH N,
1997, 40, 1201.
2
2
2
J = 6.9 Hz), 7.14 (s, 1 H), 7.28–7.48 (m, 4 H), 7.56–7.64 (m,
H), 7.71 (d, 1 H, J = 8.1 Hz), 8.60 (dd, 1 H, J = 1.5 Hz,
(
(
(
3) Rodriguez, I.; Kuehm-Caubère, C.; Vinter-Pasquier, K.;
2
Renard, P.; Pfeiffer, B.; Caubère, P. Tetrahedron Lett. 1998,
1
3
J = 8.1 Hz), 10.31 (s, 1 H, CHO). C NMR (62.5 MHz,
CDCl ): d = 13.7, 14.0 (2 CH ), 19.8, 20.3 (2 CH ), 27.4,
39, 7283.
4) Blanchard, S.; Rodriguez, I.; Kuehm-Caubère, C.; Renard,
3
3
2
30.4 (2 CH ), 41.9, 56.7 (2 CH N), 114.2 (CH), 119.5, 123.2
P.; Pfeiffer, B.; Guillaumet, G.; Caubère, P. Tetrahedron
2
2
(
2 C), 123.6, 125.3, 125.6 (3 CH), 126.2, 126.8 (2 CH),
2002, 58, 3513.
1
1
27.0 (C), 127.2, 127.4, 127.6 (3 CH) 129.5, 136.5, 142.3,
42.9, 146.4, 147.4 (6 C), 189.7 (CHO).
5) (a) Blanchard, S.; Rodriguez, I.; Caubère, P.; Guillaumet, G.
Synlett 2002, 1356. (b) Grig-Alexa, I. C.; Finaru, A. L.;
Ivan, L.; Caubère, P.; Guillaumet, G. Tetrahedron Lett.
(
(
16) Supplementary X-ray Crystallographic data: Cambridge
Crystallographic Data Centre, University Chemical Lab,
Lensfield Road Cambridge, CB2 1EW, UK; http:/
www.deposit@chemcrys.cam.ac.uk.
2004, 45, 2343.
(
6) (a) Caubère, P.; Guillaumet, G.; Rodriguez, I.; Vinter-
Pasquier, K.; Kuehm-Caubère, C.; Blanchard, S.; Atassi, G.;
Pierre, A.; Pfeiffer, B.; Renard, P. P. Eur. Pat. Appl. EP
17) (a) Brown, H. C.; Krishnamurthy, S. Tetrahedron 1979, 35,
3
67. (b) Seyden-Penne, J. Reductions by the Alumino and
Borohydrides in Organic Synthesis; VCH-Lavoisier: Paris,
991.
9
(
6986, 1999; Chem. Abstr. 2000, 132, 22978.
b) Blanchard, S.; Rodriguez, I.; Tardy, C.; Baldeyrou, B.;
Bailly, C.; Colson, P.; Houssier, C.; Léonce, S.; Kraus-
1
Synlett 2004, No. 11, 2000–2004 © Thieme Stuttgart · New York