An Efficient Synthesis of Functionalized 6,10-Dioxo-6,10-dihydro-5H-pyrido[1,2-a]quinoxalines and 6,10-Dioxo-6,10-dihydropyrido[2,1-c][1,4]benz­oxazines

Abstract

An efficient synthesis of alkyl 8-hydroxy-6,10-di­oxo-6,10-dihydro-5H-pyrido[1,2-a]quinoxaline-7-carboxylates and alkyl 8-hydroxy-6,10-dioxo-6,10-dihydropyrido[2,1-c][1,4]benzoxa­zine-7-carboxylates is described. This involves the reaction between malonyl dichloride and alkyl 2-[3,4-dihydro-3-oxo­quinoxaline 2(1H)-ylidene]acetates or alkyl 2-(2-oxo-2H-benzo[b][1,4]oxazin-3(4H)-ylidene)acetates in CH₂Cl₂ at room temperature.

malonyl dichloride - pyrido[1,2-a]quinoxaline - pyrido[2,1-c][1,4]benzoxazine - benzene-1,2-diamine - 2-aminophenol - acetylenic ester

References and Notes

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General Procedure for the Synthesis of Compounds 4
To a suspension of 3 (2 mmol) [¹8] in CH₂Cl₂ (10 mL) was added of malonyl dichloride (0.29 g, 2.1 mmol) at r.t. The reaction mixture was then stirred for 15 min. The formed precipitate was filtered off and washed with CH₂Cl₂ to afford the pure product. Compound 4a: pale yellow powder; mp 300-304 ˚C (dec.); yield 0.56 g (98%). IR (KBr): ν_max = 3450, 1729, 1693, 1655, 1490, 1418, 1365, 1306, 1258, 1106, 757 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 3.74 (3 H, s, OMe), 6.08 (1 H, s, CH), 7.12 (1 H, d, ^³ J = 7.8 Hz, CH), 7.20 (1 H, t, ^³ J = 7.9 Hz, CH), 7.30 (1 H, t, ^³ J = 8.0 Hz, CH), 9.19 (1 H, d, ^³ J = 7.8 Hz, CH), 11.76 (1 H, s, OH), 11.84 (1 H, s, NH) ppm. ^¹³C NMR (125.7 MHz, CDCl₃): δ = 52.6 (OMe), 102.9 (CH), 112.4 (C), 116.4 (CH), 121.5 (CH), 122.8 (CH), 123.9 (C), 127.3 (CH), 128.1 (C), 133.0 (C), 156.2 (COH), 162.1 (CO), 162.9 (CO), 165.3 (CO₂) ppm. MS: m/z (%) = 285 (20) [M - 1⁺], 262 (20), 236 (35), 179 (10), 123 (40), 97 (50), 83 (55), 69 (60), 57 (100), 43 (90). Anal. Calcd (%) for C₁₄H₁₀N₂O₅ (286.24): C, 58.75; H, 3.52; N, 9.79. Found: C, 58.60; H, 3.44; N, 9.65. Compound 4d: pale yellow powder; mp 298-300 ˚C (dec.); yield 0.55 g (97%). IR (KBr) ν_max = 3505, 1764, 1721, 1661, 1618, 1499, 1408, 1333, 1304, 1294, 1106, 759 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 3.79 (3 H, s, OMe), 6.12 (1 H, s, CH), 7.27 (1 H, t, ^³ J = 7.0 Hz, CH), 7.30 (1 H, d, ^³ J = 7.9 Hz, CH), 7.33 (1 H, t, ^³ J = 8.0 Hz, CH), 9.18 (1 H, d, ^³ J = 8.6 Hz, CH), 12.01 (1 H, s, OH) ppm.^¹³C NMR (125.7 MHz, CDCl₃): δ = 52.5 (OMe), 104.1 (CH), 114.8 (C), 116.8 (CH), 120.6 (CH), 123.1 (C), 124.3 (CH), 127.0 (CH), 127.9 (C), 141.1 (C), 154.2 (COH), 161.4 (CO), 161.5 (CO), 164.1 (CO₂) ppm. Anal. Calcd (%) for C₁₄H₉NO₆ (287.22): C, 58.54; H, 3.16; N, 4.88. Found: C, 58.60; H, 3.14; N, 4.85. Compound 4g: yellow powder; mp 298-301 ˚C (dec.); yield 0.58 g (98%). IR (KBr) ν_max = 3440, 1764, 1722, 1665, 1621, 1455, 1324, 1286, 1250, 1107, 765 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 2.32 (3 H, s, Me), 3.78 (3 H, s, OMe), 6.10 (1 H, s, CH), 7.15 (1 H, d, ^³ J = 8.3 Hz, CH), 7.19 (1 H, d, ^³ J = 8.3 Hz), 9.03 (1 H, s, CH), 11.99 (1 H, s, OH) ppm. ^¹³C NMR (125.7 MHz, CDCl₃): δ = 20.9 (Me), 52.4 (OMe), 104.1 (CH), 114.8 (C), 116.5 (CH), 120.7 (CH), 122.6 (C), 127.4 (CH), 127.9 (C), 133.5 (C), 139.0 (C), 154.3 (C-OH), 161.3 (CO), 161.4 (CO), 164.1 (CO₂) ppm. Anal. Calcd (%) for C₁₅H₁₁NO₆ (301.25): C, 59.81; H, 3.68; N, 4.65. Found: C, 59.80; H, 3.65; N, 4.65.
All other novel compounds isolated possessed spectroscopic and analytical data in keeping with their proposed structures.

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