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Synlett 2010(11): 1682-1684  
DOI: 10.1055/s-0029-1220126
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Reactions of Heterocyclic Ketene Aminals with 2-[3-Oxoisobenzofuran-1(3H)-ylidene]malononitrile: Synthesis of Novel Polyfunctionalized 1,4-Dihydropyridine-Fused 1,3-Diazaheterocycles

Wen-Yuan Xua,b, Yue-Mei Jiab, Jing-Kui Yang*a, Zhi-Tang Huang*b, Chu-Yi Yu*b
a College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049, P. R. of China
b Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. of China
Fax: +86(10)82616433; e-Mail: yucy@iccas.ac.cn;
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Publication History

Received 8 April 2010
Publication Date:
01 June 2010 (online)

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Abstract

An efficient method has been developed for the synthesis of a novel kind of polyfunctionalized 1,4-dihydropyridine-fused 1,3-diazaheterocycles via the reactions of heterocyclic ketene aminals (HKAs) with 2-[3-oxoisobenzofuran-1(3H)-ylidene]malono­nitrile.

Key words

heterocyclic ketene aminals - polyfunctionalized - 1,4-dihydropyridine-fused 1,3-diazaheterocycles - synthesis

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22

General Procedure for the Synthesis of 3: Heterocyclic ketene aminals 1 (1 mmol) and 2-[3-oxoisobenzofuran-1 (3H)-ylidene]malononitrile (2; 1 mmol) were stirred in DMF (5 mL) at 120 ˚C until the reaction was complete as monitored by TLC (ca. 2-12 h). After the reaction mixture was cooled to r.t., the solvents were removed in vacuo and the resulting solids were subjected to recrystallization (MeOH-Et2O or MeCN) to provide the desired fused heterospiro compounds 3.
Compound 3f: yellow solid; mp 306-307 ˚C. IR (KBr): 3363 (m), 3331 (m), 2211 (m), 1633 (s), 1603 (s), 1582 (s), 1558 (s), 1508 (m), 1370 (s), 1311 (s), 931 (m), 849 (w), 763 (m), 732 (m), 678 (m), 652 (m) cm-¹. ¹H NMR (300 MHz, DMSO-d 6): δ = 7.73 (d, J = 7.5 Hz, 1 H), 7.53-7.63 (m, 4 H), 7.44-7.47 (m, 4 H), 7.30-7.40 (m, 2 H), 7.20-7.25 (m, 1 H), 7.04 (d, J = 7.2 Hz, 1 H), 4.03-4.22 (m, 2 H), 3.79-3.94 (m, 2 H). ¹³C NMR (75 MHz, DMSO-d 6): δ = 192.0, 166.8, 154.4, 152.7, 142.9, 139.2, 137.7, 132.5, 137.0, 130.6, 130.2, 129.5, 129.1, 128.9, 128.3, 128.0, 126.7, 125.8, 117.1, 105.1, 77.9, 48.6, 45.4. HRMS (ESI): m/z [M + H]+ calcd for C28H21N4O3 +: 461.1608; found: 461.1609. Compound 3o: yellow solid; mp 205-207 ˚C. IR (KBr): 3282 (m), 3061 (m), 2212 (m), 1631 (s), 1604 (s), 1560 (s), 1528 (s), 1480 (m), 1376 (s), 1337 (s), 1280 (m), 1068 (m), 927 (m), 850 (m), 776 (m), 676 (m) cm-¹. ¹H NMR (300 MHz, DMSO-d 6): δ = 7.63 (d, J = 6.9 Hz, 1 H), 7.17-7.31 (m, 6 H), 7.00 (d, J = 6.6 Hz, 1 H), 4.01-4.02 (m, 2 H), 3.40-3.42 (m, 2 H), 2.00-2.03 (m, 2 H). ¹³C NMR (75 MHz, DMSO-d 6): δ = 192.7, 166.8, 156.1, 154.5, 152.1, 139.7, 137.2, 132.4, 130.6, 130.2, 130.1, 129.9, 128.5, 124.2, 117.2, 103.2, 83.5, 48.6, 42.8, 18.6. HRMS (ESI): m/z [M + H]+ calcd for C23H18N4O3Br+: 477.0571; found: 477.0562.