PAPER
Enantioselective Synthesis of 2,3-Dihydroquinazolinones
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(see tables), followed by aldehyde (360 μmol), and the mixture was
stirred until the reaction was complete as ascertained by TLC. The
product was purified by using a small pad of silica gel (60–100
mesh) with PE–EtOAc (1:1) as eluent to afford the corresponding
2,3-dihydroquinazolinone as a colorless solid. Analytical data for
all new compounds (13a, 13c, 15e) are provided below, and charac-
terization data for other reported compounds are provided in detail
in the Supporting Information.
HRMS (ESI): m/z [M + H]+ calcd for C21H16N2O3: 345.1239;
found: 345.1233.
Acknowledgment
We acknowledge DST (SR/S1/OC-60/2006), Government of India,
New Delhi for financial support. M.P. thanks CSIR for a research
fellowship. We thank Sophisticated Analytical Instrument Facility
(SAIF) and the Department of Chemistry, IIT Madras for the analy-
tical data.
(S)-2-Ethyl-2,3-dihydroquinazolin-4(1H)-one (13a)
Colorless solid; yield: 42 mg (80%); mp 148 °C.
[α]D25 +75.2 (c 1.0, THF).
HPLC (OD-H column; n-hexane–i-PrOH, 80:20; flow rate = 0.8
mL·min–1): tR = 11.32 (minor enantiomer), 9.77 min (major enan-
tiomer); er 89:11.
Supporting Information for this article is available online at
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Rf = 0.3 (PE–EtOAc, 1:1).
References
FTIR (KBr): 3294, 3081, 2958, 1654, 1613, 1506, 1385, 1264,
1153, 755, 699 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.89 (dd, J = 8, 1.5 Hz, 1 H),
7.34–7.30 (m, 1 H), 6.88–6.85 (m, 1 H), 6.69 (d, J = 8.0 Hz, 1 H),
6.43 (br s, 1 H), 4.88–4.85 (m, 1 H), 1.86–1.81 (m, 2 H), 1.08 (t,
J = 7.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 165.43, 147.44, 133.85, 128.57,
119.34, 115.86, 114.69, 66.43, 28.59, 8.28.
HRMS (ESI): m/z [M + Na]+ calcd for C10H12N2O: 199.0847;
found: 119.0845.
(1) (a) Russel, H. E.; Alaimo, R. J. J. Med. Chem. 1972, 15, 335.
(b) Neil, G. L.; Li, L. H.; Buskirk, H. H.; Moxley, T. E.
Cancer Chemother. Rep. 1972, 56, 163. (c) Cooper, E. R. A.;
Jackson, H. J. Reprod. Fertil. 1973, 34, 445.
(d) Kozhevnikov, Y. V.; Smirrnova, N. N.; Zalesov, V. S.;
Gradel, I. I. Pharm. Chem. J. 1981, 15, 403.
(e) Sadanandam, Y. S.; Ram Mohan Reddy, K.; Bhaskar
Rao, A. Eur. J. Med. Chem. 1987, 22, 169. (f) Kuo, S. C. H.;
Lee, Z.; Juang, J. P.; Lin, Y. T.; Wu, T. S.; Chang, J. J.;
Lednicer, D.; Paull, K. D.; Lin, C. M.; Hamel, E.; Lee, K. H.
J. Med. Chem. 1993, 36, 1146. (g) Levin, J. I.; Chan, P. S.;
Bailey, T.; Katocs, A. S.; Venkatesan, A. M. Bioorg. Med.
Chem. Lett. 1994, 4, 1141. (h) Hamel, E.; Lin, M.; Plowman,
C. J.; Wang, H. K.; Lee, K. H.; Paull, K. D. Biochem.
Pharmacol. 1996, 51, 53. (i) Hour, M. J.; Huang, L. J.; Kuo,
S. C.; Xia, Y.; Bastow, K.; Nakanishi, Y.; Hamel, E.; Lee, K.
H. J. Med. Chem. 2000, 43, 4479. (j) Xu, Z.; Zhang, Y.; Fu,
H.; Zhong, H.; Hong, K.; Zhu, W. Bioorg. Med. Chem. Lett.
2011, 21, 4005.
(S)-2-Pentyl-2,3-dihydroquinazolin-4(1H)-one (13c)
Colorless solid; yield: 52 mg (79%); mp 154 °C.
[α]D25 +79.7 (c 1.0, THF).
HPLC (OD-H column; n-hexane–i-PrOH, 90:10; flow rate = 0.8
mL·min–1): tR = 23.45 (minor enantiomer), 20.66 min (major enan-
tiomer); er 88:12.
Rf = 0.35 (PE–EtOAc, 1:1).
(2) (a) Agranat, I.; Caner, H.; Caldwell, J. Nat. Rev. Drug
Discovery 2002, 1, 753. (b) Kasprzyk-Hordern, B. Chem.
Soc. Rev. 2010, 39, 4466. (c) Agranat, I.; Wainschtein, S. R.
Drug Discovery Today 2010, 15, 163.
(3) Chinigo, G. M.; Paige, M.; Grindrod, S.; Hamel, E.;
Dakshanamurthy, S.; Chruszcz, M.; Minor, W.; Brown, M.
L. J. Med. Chem. 2008, 51, 4620.
(4) Selected references for the synthesis of 2,3-DHQZs:
(a) Chen, J. X.; Wu, H.; Hua, Y.; Su, W. K. Chin. Chem.
Lett. 2007, 18, 536. (b) Chen, J.; Su, W.; Wu, H.; Liu, M.;
Jin, C. Green Chem. 2007, 9, 972. (c) Chen, J.; Wu, D.; He,
F.; Liu, M.; Huayue, D.; Ding, J.; Su, W. Tetrahedron Lett.
2008, 49, 3814. (d) Allameh, S.; Heravi, M. M.; Hashemi,
M. M.; Bamoharram, F. F. Chin. Chem. Lett. 2011, 22, 131;
and references cited therein.
(5) (a) Cheng, X.; Vellalath, S.; Goddard, R.; List, B. J. Am.
Chem. Soc. 2008, 130, 15786. (b) Rueping, M.; Antonchick,
A. P.; Sugiono, E.; Grenader, K. Angew. Chem. Int. Ed.
2009, 48, 908.
FTIR (KBr): 3329, 3206, 3069, 2953, 1643, 1614, 1507, 1387,
1261, 1152, 752, 690 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.91 (d, J = 1.5 Hz, 1 H), 7.35–
7.28 (m, 1 H), 6.90–6.87 (m, 1 H), 6.69 (d, J = 8.0 Hz, 1 H), 6.16
(br s, 1 H), 4.91 (t, J = 6 Hz, 1 H), 1.80–1.77 (m, 2 H), 1.38–1.36
(m, 5 H), 0.95–0.92 (m, 4 H).
13C NMR (125 MHz, CDCl3): δ = 165.37, 147.42, 133.89, 128.63,
119.46, 115.91, 114.74, 65.38, 35.59, 31.45, 23.72, 22.49, 13.91.
HRMS (ESI): m/z [M + Na]+ calcd for C13H18N2O: 241.1317;
found: 241.1311.
(S)-2-(1,3-Benzodioxol-5-yl)-3-phenyl-2,3-dihydroquinazolin-
4(1H)-one (15e)
Colorless solid; yield: 71 mg (70%); mp 239 °C.
[α]D25 +97.1 (c 1.0, THF).
HPLC (OD-H column; n-hexane–i-PrOH, 80:20; flow rate = 0.8
mL·min–1): tR = 32.35 (minor enantiomer), 22.42 min (major enan-
tiomer); er 78:22.
(6) Prakash, M.; Kesavan, V. Org. Lett. 2012, 14, 1896.
(7) Selected references for pybox: (a) Nishiyama, H.;
Sakaguchi, H.; Nakamura, T.; Horlhata, M.; Kondo, M.;
Itoh, K. Organometallics 1989, 8, 846. (b) Evans, D. A.;
Murry, J. A.; Kozlowski, M. C. J. Am. Chem. Soc. 1996, 118,
5814. (c) Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev.
2003, 103, 3119. (d) Poisson, T.; Yamashita, Y.; Kobayashi,
S. J. Am. Chem. Soc. 2010, 132, 7890. (e) Hanhan, N. V.;
Sahin, A. H.; Chang, T. W.; Fettinger, J. C.; Franz, A. K.
Angew. Chem. Int. Ed. 2010, 49, 744. (f) Singh, P. K.; Singh,
V. K. Org. Lett. 2010, 12, 80. (g) Zeng, T.; Yang, L.;
Hudson, R.; Song, G.; Moores, A. R.; Li, C.-J. Org. Lett.
Rf = 0.3 (PE–EtOAc, 3:1).
FTIR (KBr): 3297, 3039, 2928, 1639, 1614, 1500, 1450, 1393,
1244, 1035, 937, 856, 697 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 7.72 (d, J = 7.5 Hz, 1 H), 7.55
(m, 1 H), 7.34 (t, J = 8 Hz, 2 H), 7.30–7.25 (m, 3 H), 7.20 (t, J = 7.5
Hz, 1 H), 6.93 (s, 1 H), 6.81 (s, 2 H), 6.77–6.71 (m, 2 H), 6.20 (d,
J = 2.5 Hz, 1 H), 5.97 (d, J = 4.5 Hz, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 162.73, 147.82, 147.66,
147.02, 141.2, 135.07, 134.23, 129.06, 128.40, 126.72, 126.28,
120.74, 118.00, 115.76, 115.26, 108.26, 107.30, 101.64, 72.85.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2265–2272