A Synthesis of Spirocyclic Oxazinoisoquinolines and Oxazinoquinolines Bearing Thiazolopyrimidine Moieties

Abstract

The reaction of isoquinoline or quinoline with dialkyl acetylenedicarboxylates in the presence of alkyl 2-{3,5-dioxo-5H-thiazolo[3,2-a]pyrimidin-2(3H)-ylidene}acetates (generated in situ from acetylenedicarboxylates and 2-thiouracils) led to dialkyl 2-(2-alkoxy-2-oxoethylidene)-5-oxo-2H,5H,11b′H-spiro{thiazolo[3,2-a]pyrimidine-3,2′-[1,3]oxazino[2,3-a]isoquinoline}-3′,4′-dicarboxylates or dialkyl 2-(2-alkoxy-2-oxoethylidene)-5-oxo-2H,4a′H,5H-spiro{thiazolo[3,2-a]pyrimidine-3,2′-[1,3]oxazino[3,2-a]quinoline}-1′,2′-dicarboxylates in good yields. The structure of the target compounds was confirmed by X-ray diffraction study.

Key words

Huisgen’s 1,4-dipole - N-heterocycles - acetylenic esters - spiro compounds - thiouracil

• References and Notes

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• 16 General Procedure for the Preparation of Compounds 4 and 6 To a stirred solution of 2 (2 mmol) and 3 (1 mmol) in toluene (10 mL) at reflux was added dropwise a solution of isoquinoline or quinoline (0.286 g, 1 mmol) in toluene (4 mL). After completion of the reaction as evidenced by TLC, the solvent was evaporated and the residue was recrystallized from AcOEt/n-hexane (1:3) to afford the pure product. Dimethyl 2-(2-Methoxy-2-oxoethylidene)-5-oxo-2H,5H,11b′H-spiro[thiazolo[3,2-a]pyrimidine-3,2′-[1,3]oxazino[2,3-a]isoquinoline]-3′,4′-dicarboxylate (4a) Yellow crystals; mp 88–90 °C; yield 0.43 g (85%). IR (KBr): ν_max = 1748 (C=O), 1711 (C=O), 1628 (C=O) cm^–1. ¹H NMR: δ = 3.63 (3 H, s, MeO), 3.77 (3 H, s, MeO), 3.96 (3 H, s, MeO), 5.95 (1 H, d, ³J = 7.8 Hz, CH), 6.13 (1 H, s, CH), 6.25 (1 H, d, ³ J = 6.5 Hz, CH), 6.45 (1 H, d, ³ J = 7.7 Hz, CH), 7.16 (1 H, d, ³ J = 7.6 Hz, CH), 7.30 (1 H, d, ³ J = 7.6 Hz, CH), 7.34–742 (2 H, m, CH), 7.51 (1 H, s, CH), 7.84 (1 H, d, ³ J = 6.5 Hz, CH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 52.5 (MeO), 52.6 (MeO), 54.1 (MeO), 83.3 (CH), 95.9 (C), 107.0 (CH), 108.9 (C), 112.4 (CH), 113.1 (CH), 123.5 (CH), 125.8 (C), 126.0 (CH), 128.0 (CH), 128.5 (CH), 129.4 (C), 130.4 (CH), 146.1 (C), 153.9 (CH), 154.3 (C), 161.4, 162.8, 162.9, 163.2, 166.7 (5 C, C=O and C=N). MS (EI, 70 eV): m/z (%) = 509 (15) [M⁺], 386 (27), 321 (100), 294 (20), 281 (17), 254 (50), 226 (36), 129 (80). Anal. Calcd for C₂₄H₁₉N₃O₈S (509.49): C, 56.58; H, 3.76; N, 8.25%. Found: C, 56.42; H, 3.78; N, 8.27%. Dimethyl 2-(2-Methoxy-2-oxoethylidene)-5-oxo-2H,4a′H,5H-spiro{thiazolo[3,2-a]pyrimidine-3,3′-[1,3]oxazino[3,2-a]quinoline}-1′,2′-dicarboxylate (6a) Yellow crystals; mp 75–77 °C; yield 0.44 g (87%). IR (KBr): ν_max = 1735 (C=O), 1717 (C=O), 1689 (C=O) cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.65 (3 H, s, MeO), 3.70 (3 H, s, MeO), 3.92 (3 H, s, MeO), 5.99 (1 H, s, CH), 5.99 (1 H, dd, ³ J = 9.9, 4.3 Hz, CH), 6.22 (1 H, d, ³ J = 6.7 Hz, CH), 6.80 (1 H, d, ³ J = 4.3 Hz, CH), 6.89 (1 H, d, ³ J = 9.8 Hz, CH), 6.99 (1 H, d, ³ J = 8.1 Hz, CH), 7.09 (1 H, t, ³ J = 7.4 Hz, CH), 7.28 (1 H, d, ³ J = 8.1 Hz, CH), 7.33 (1 H, t, ³ J = 7.4 Hz, CH), 7.80 (1 H, d, ³ J = 6.7 Hz, CH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 52.5 (MeO), 52.6 (MeO), 54.1 (MeO), 83.3 (CH), 95.9 (C), 107.0 (CH), 108.9 (C), 112.4 (CH), 113.1 (CH), 123.5 (CH), 125.8 (C), 126.0 (CH), 128.0 (CH), 128.5 (CH), 129.4 (C), 130.4 (CH), 146.1 (C), 153.9 (CH), 154.3 (C), 161.4, 162.8, 162.9, 163.2, 166.7 (5 C, C=O and C=N). MS (EI, 70 eV): m/z (%) = 509 (15) [M⁺], 386 (27), 321 (100), 294 (20), 281 (17), 254 (50), 226 (36), 129 (80). Anal. Calcd for C₂₄H₁₉N₃O₈S (509.49): C, 56.58; H, 3.76; N, 8.25%. Found: C, 56.37; H, 3.75; N, 8.22%.
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• 18 CCDC-1541004 and CCDC-1541008 contain the supplementary crystallographic data for 4b and 6d, respectively. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
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