Epoxidation of 1,2-Dihydroquinoline: Synthesis of (–)-(R)-Sumanirole
ingland, P. J. Bédard, R. M. Huff, J. Pharmacol. Exp. Ther.
2005, 314, 1248–1256.
135.6, 127.1, 126.3, 120.5, 119.0, 117.7, 106.3, 45.6 (2 C), 29.3 ppm.
IR (KBr): ν = 3300, 1684 cm–1. MS (EI): m/z (%) = 189 (100)
˜
[M]+·, 171 (35), 147 (30). HRMS (EI): calcd. for C10H11N3O
189.0902; found 189.0903.
[3]
For the structure determination, see: Y. Ito, K. Ishida, S. Ok-
ada, M. Murakami, Tetrahedron 2004, 60, 9075–9080; for the
Synthesis see: a) K. Gademann, Y. Bethuel, Org. Lett. 2004, 6,
4707–4710; b) K. Gademann, Y. Bethuel, Angew. Chem. 2004,
116, 3389; Angew. Chem. Int. Ed. 2004, 43, 3327–3329; c) Y.
Bethuel, K. Gademann, J. Org. Chem. 2005, 70, 6258–6264.
For the asymmetric Synthesis see: a) M. Guinó, P. H. Phua, J.-
C. Caille, K. K. Hii, J. Org. Chem. 2007, 72, 6290–6293; b) H.
Liu, G. Dagousset, G. Masson, P. Retailleau, J. Zhu, J. Am.
Chem. Soc. 2009, 131, 4598–4599.
For the Synthesis see: a) P. D. Leeson, R. W. Carling, K. W.
Moore, A. M. Moseley, J. D. Smith, G. Stevenson, T. Chan, R.
Baker, A. C. Foster, S. Grimwood, J. A. Kemp, G. R. Marshall,
K. Hoogsteen, J. Med. Chem. 1992, 35, 1954–1968; b) M. Tak-
amura, K. Funabashi, M. Kanai, M. Shibasaki, J. Am. Chem.
Soc. 2001, 123, 6801–6808.
(5R)-5-(Formylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-
1(2H)-one (40): To a solution of amine 39 (0.170 g, 0.9 mmol) in
acetonitrile (0.9 mL) was added a preformed mixture of Ac2O/
HCO2H (1:1, 0.28 mL) and Ac2O (0.570 mL). The resulting solu-
tion was stirred under argon at 20 °C for 2 h and then concentrated
in vacuo. To the residue was added MeOH (15 mL), and the solu-
tion was stirred at 20 °C for 1 h. After concentration in vacuo, the
crude product was purified by silica gel column chromatography
(CH2Cl2/MeOH, 95:5; Rf = 0.12) to give formamide 40 (0.150 g,
77%) as an orange solid; m.p. 215 °C. [α]2D0 = –153 (c = 0.14,
CHCl3). 1H NMR (300 MHz, [D6]DMSO): δ = 10.74 (s, 1 H), 8.33
(d, J = 6.0 Hz, 1 H), 8.02 (s, 1 H), 6.96 (dd, J = 9.0, 8.8 Hz, 1 H),
6.87 (d, J = 8.8 Hz, 1 H), 6.79 (d, J = 9.0 Hz, 1 H), 4.46 (m, 1 H),
3.70 and 3.90 (ABX system, J = 12.0, 6.0, 3.0 Hz, 2 H), 2.86 and
3.07 (ABX system, J = 18.0, 6.0, 3.0 Hz, 2 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 160.9, 153.7, 126.9, 126.5, 120.7, 119.3,
[4]
[5]
[6]
[7]
a) I. Gallou-Dagommer, P. Gastaud, T. V. RajanBabu, Org.
Lett. 2001, 3, 2053–2056; b) A. R. Jagdale, R. S. Reddy, A. Su-
dalai, Org. Lett. 2009, 11, 803–806.
For a review of the synthetic routes to sumanirole, see: a)
P. G. M. Wuts, Curr. Opin. Drug Discovery Dev. 1999, 2, 557–
564; for more recent syntheses, see: b) P. G. M. Wuts, R. L. Gu,
J. M. Northuis, T. A. Kwan, D. M. Beck, M. J. White, Pure
Appl. Chem. 2002, 74, 1359–1368; c) D. Gala, V. H. Dahanu-
kar, J. Eckert, B. S. Lucas, D. P. Schumacher, I. A. Zavialov,
Org. Process Res. Dev. 2004, 8, 754–768; d) see also ref.[6b]
M. Pauvert, S. Collet, M.-J. Bertrand, A. Guingant, M. Evain,
Tetrahedron Lett. 2005, 46, 2983–2987.
J. V. Cooney, J. Heterocycl. Chem. 1983, 20, 823–837 and refer-
ences cited therein. An improved method is reported in the
Experimental Section for optimized preparations of 8a.
F. D. Popp, L. E. Katz, C. W. Klinowski, J. M. Wefer, J. Org.
Chem. 1968, 33, 4447–50.
116.1, 106.6, 42.0, 41.4, 29.1 ppm. IR (KBr): ν = 1576–1727 cm–1.
˜
MS (EI): m/z (%) = 217 (16) [M]+·, 171 (100). HRMS (EI): calcd.
for C11H11N3O2 217.0851; found 217.0859.
(5R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-
1(2H)-one [(R)-1]: To a stirred solution of formamide 40 (0.130 g,
0.6 mmol) in anhydrous THF (0.330 mL) was added dropwise a
solution of BH3·Me2S complex (2 m solution in THF, 0.670 mL,
1.4 mmol). The stirring was continued at 20 °C under argon for
3 h. After concentration of the reaction mixture, a solution of HCl
(2 n solution) in Et2O (2.5 mL) and MeOH (2 mL) was added. The
resulting solution was heated at reflux for 2 h. After cooling to
20 °C, the solution was concentrated in vacuo. The solid residue
was triturated with a mixture of MeOH/Et2O (1:1) and then filtered
to give (R)-1·HCl as a brown solid (0.77 g, 63%). M.p. 297 °C (cf.
308 °C,[24a] Ͼ310 °C[24b]). [α]2D0 = –33.5 (c = 0.1, MeOH) (cf.
[8]
[9]
[10]
[11]
X-ray crystal structure data: C17H14N2O3, Mr = 294.3, mono-
clinic, C2/c,
a = 21.2550(5) Å, b = 6.0702(2) Å, c =
23.8302(6) Å, α = 106.7519(16), V = 2944.14(14) Å3, Z = 8,
ρcalcd. = 1.3275 gcm–3, µ = 0.093 mm–1, F(000) = 1266, color-
less block, 0.15ϫ0.12ϫ0.10 mm, 2θmax = 54.8°, T = 150 K,
1
–35.1,[24a] –30.3[24b]). H NMR (300 MHz, D2O): δ = 7.05 (dd, J =
16562 reflections, 3302 unique (99% completeness), Rint
=
0.1099, 242 parameters, GOF = 1.23, wR2 = 0.1098, R =
0.0498 for 1934 reflections with I Ͼ 2σ(I). CCDC-871760 con-
tains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
The stereochemical assignments for compounds 9a and 10a
could be safely made after the structure of 11 was revealed by
single-crystal X-ray diffraction. The stereochemical assign-
ments for 9b and 10b were made by analogy (see also ref.[13]).
The mCPBA epoxidation of 8a had already been studied, but
the stereochemistry of 9a was erroneously assigned (syn instead
of anti arrangement) on the basis of NMR considerations: M.
Kratzel, R. Hiessböck, Monatsh. Chem. 1993, 124, 1207–1209.
R. F. Collins, T. Henshall, J. Am. Chem. Soc. 1958, 80, 159–
161.
R. L. Cobb, W. E. McEwen, J. Am. Chem. Soc. 1955, 77, 5042–
5048. An improved preparation of amide 12 and ester 13 is
described in the Experimental Section.
The structure of 15 was firmly established by single-crystal X-
ray diffraction: M. Evain, M. Pauvert, S. Collet, A. Guingant,
Acta Crystallogr., Sect. E 2004, 60, 754–755.
D. A. Evans, M. M. Faul, M. T. Bilodeau, J. Am. Chem. Soc.
1994, 116, 2742–2753.
P. Dauban, R. H. Dodd, J. Org. Chem. 1999, 64, 5304–5307.
M. Evain, L. Jean-Gérard, S. Collet, A. Guingant, Acta Crys-
tallogr., Sect. E 2007, 63, o4023.
8.0 Hz, 1 H), 6.98 (d, J = 8.0 Hz, 1 H), 6.95 (d, J = 8.0 Hz, 1 H),
3.99 (m, 1 H), 3.96 and 4.17 (ABX system, J = 13.3, 2.9, Ͻ1 Hz,
2 H), 3.13 and 3.27 (ABX system, J = 17.3, 2.8, 2.5 Hz, 2 H), 2.70
(s, 3 H) ppm. 13C NMR (75 MHz, D2O): δ = 155.0, 126.0 (2 C),
122.7, 120.5, 113.9, 108.7, 52.2, 39.3, 31.0, 25.9 ppm. IR (KBr): ν
˜
= 1680 cm–1. MS (EI): m/z (%) = 203 (100) [M]+·, 171 (28), 162
[12]
[13]
(30). HRMS (EI): calcd. for C11H13N3O 203.1059; found 203.1062.
Supporting Information (see footnote on the first page of this arti-
cle): General experimental methods, experimental procedures, ana-
lytical data for compounds 8a, 9a, 9b, 10a, 10b, 11–15, 22a–22c,
1
and 23–26, significant H and 13C NMR spectra of all new com-
pounds, and crystallographic data of compound 11.
[14]
[15]
Acknowledgments
We thank Aurélien Planchat for the X-ray crystallographic struc-
ture determination.
[16]
[17]
[1] a) A. R. Katritzky, S. Rachwal, B. Rachwal, Tetrahedron 1996,
52, 15031–15068; b) V. Sridharan, P. A. Suryavanshi, J. C.
Menéndez, Chem. Rev. 2011, 111, 7157–7259.
[2] a) R. F. Heier, L. A. Dolak, J. N. Duncan, D. K. Hyslop, M. F.
Lipton, I. J. Martin, M. A. Mauragis, M. F. Piercey, N. F.
Nichols, P. J. K. D. Schreur, M. W. Smith, M. W. Moon, J.
Med. Chem. 1997, 40, 639–646; b) R. B. McCall, K. L. Look-
[18]
[19]
[20]
A preliminary communication based on this strategy has been
disclosed. For this report, see: L. Jean-Gérard, F. Macé, H.
Eur. J. Org. Chem. 2012, 4240–4248
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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