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Synlett 2018; 29(08): 1107-1111
DOI: 10.1055/s-0036-1591550
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Chromeno[4′,3′:4,5]pyrido[1,2-a]pyrazines and -diazepines by the Reaction of Substituted 2-(3-Acetyl-2-oxo-2H-chromen-4-yl)fumarates with 1,n-Diamines

Abdolali Alizadeh*
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Parinaz Jamal
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 15 December 2017

Accepted after revision: 11 February 2018

Publication Date:
04 April 2018 (online)

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Abstract

A two-step sequence was developed for the synthesis of chromeno[4′,3′:4,5]pyrido[1,2-a]pyrazine-13-carboxylates and -diazepine-14-carboxylates by the reaction of substituted dimethyl 2-(3-acetyl-2-oxo-2H-chromen-4-yl)fumarates with 1,n-diamines at room temperature. Advantages of this protocol include ease of handling and the absence of a metal catalyst.

Key words

dimethyl acetyloxochromenfumarates - chromenopyrido­pyrazinecarboxylates - chromenopyridodiazepinecarboxylates - cyclization - polycyclic heterocycles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591550.
  • Supporting Information
 

  • References and Notes

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  • 28 Dimethyl 2-(3-Acetyl-2-oxo-2H-chromen-4-yl)fumarates 3a–c; General Procedure A solution of dimethyl acetylenedicarboxylate (1 mmol) in CH2Cl2 (3 mL) was added dropwise over 15 min to a magnetically stirred solution of the appropriate 3-acetylcoumarin (1 mmol) and Ph3P (1 mmol) in anhyd CH2Cl2 (3 mL) at r.t., and the mixture was stirred for 4 h. When the reaction was complete, the solvent was removed and the product was precipitated by adding hexane, collected by filtration, and washed with EtOH. Dimethyl (2E)-2-(3-Acetyl-2-oxo-2H-chromen-4-yl)but-2-enedioate (3a) Cream powder; yield: 0.31 g (95%); mp 111–113 °C. IR (KBr): 1720 (C=O), 1598 and 1533 (Ar) cm–1. 1H NMR (300.13 MHz, CDCl3): δ = 2.56 (s, 3 H, CH3), 3.55 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 7.09 (s, 1 H, CH3 of butenedioate), 7.23 (t, 3 J HH = 8.6 Hz, 1 H, CH6), 7.33 (d, 3 J HH = 7.8 Hz, 1 H, CH8), 7.35 (d, 3 J HH = 7.8 Hz, 1 H, CH5), 7.57 (t, 3 J HH = 7.7 Hz, 1 H, CH7). 13C NMR (75.46 MHz, CDCl3) δ = 30.9 (CH3), 52.3 (OCH3), 53.42 (OCH3), 117.2 (C3), 118.4 (CH8), 123.7 (C4a), 125.1 (CH6), 126.9 (CH7), 128.3 (CH5), 133.8 (C2 of butenedioate), 141.3 (CH3 of butenedioate), 152.3 (C8a), 153.7 (C4), 158.8 (C2=O), 163.8 (CO2Me), 164.2 (CO2Me), 198.1 (C=O). MS (EI, 70 eV): m/z (%) = 331 [M + 1]+ (2), 330 [M]+ (1), 288 (14), 287 (71), 272 (46), 271 (100), 257 (16), 243 (15), 229 (11), 227 (12), 213 (12), 197 (23), 113 (18), 59 (17), 43 (30). Anal. Calcd for C17H14O7 (330.07): C, 61.82; H, 4.27. Found: C, 61.79; H, 4.29. Crystal data for 3a (C17H14NO7): MW = 330.28, monoclinic, P21/n, a = 13.8388(18) Å, b = 8.6354(8) Å, c = 14.095(2) Å, β = 113.541(17), V = 1544.2(3) Å3, Z = 4, D c = 1.421 mg/m3, F (000) = 688; crystal dimensions, 0.45 × 0.40 × 0.38 mm; radiation, Mo Kα (λ = 0.71073 Å). 2.84 ≤ 2 ≤ 25.09, intensity data were collected at 293(2) K with a Bruker APEX area-detector diffractometer by employing an ω/2θ scanning technique in the range –16 ≤ h ≤ 13, –10 ≤ k ≤ 8, –16 ≤ l ≤ 15. The structure was solved by direct methods; all nonhydrogen atoms were positioned, and anisotropic thermal parameters were refined from 1699 observed reflections with R (into) = 0.1124 by a full-matrix least-squares technique, converging to R = 0.0754 and R aw = 0.2308 [I > 2σ (I)]. Dimethyl (2E)-2-(3-Acetyl-6-bromo-2-oxo-2H-chromen-4-yl)but-2-enedioate (3b) Cream powder; yield: 0.37 g (92%); mp 135–137 °C. IR (KBr): 1722 (C=O), 1601 and 1530 (Ar) cm–1. 1H NMR (300.13 MHz, CDCl3): δ = 2.58 (s, 3 H, CH3), 3.64 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3), 7.13 (s, 1 H, CH3 of butenedioate), 7.30 (d, 3 J HH = 8.8 Hz, 1 H, CH8), 7.50 (d, 4 J HH = 2.0 Hz, 1 H, CH5), 7.78 (dd, 3 J HH = 8.8 Hz, 4 J HH = 2.1 Hz, 1 H, CH7). 13C NMR (75.46 MHz, CDCl3): δ = 30.9 (CH3), 52.6 (OCH3), 53.6 (OCH3), 117.9 (C3), 119.0 (CH8), 120.0 (C-Br), 124.5 (C4a), 128.8 (CH7), 129.0 (CH5), 136.5 (C2 of butenedioate), 140.8 (CH3 of butenedioate), 151.0 (C8a), 152.5 (C4), 158.2 (C2=O), 163.6 (CO2Me), 164.2 (CO2Me), 197.8 (C=O). Anal. Calcd for C17H13BrO7 (409.19): C, 49.90; H, 3.20. Found: C, 49.87; H, 3.22.
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  • 32 Polycyclic Heterocycles 8a–g; General Procedure A solution of the appropriate diester 3 (1 mmol) and 1,n-diamine 7 (1 mmol) in CH2Cl2 was magnetically stirred at r.t. for 2 h until the reaction was complete (TLC). The mixture was then filtered, and the residue was purified by column chromatography [silica gel (Merck 230–240 mesh), EtOAc]. Methyl 7-Methyl-6,12-dioxo-10,11,12,12a-tetrahydro-6H,9H-chromeno[4′,3′:4,5]pyrido[1,2-a]pyrazine-13-carboxylate (8a) Yellow powder; yield: 0.214 g (63%); mp 170 °C (dec.). IR (KBr): 3425 (NH), 1686 (C=O), 1620 (NCO), 1527 and 1458 (Ar), 1221 (C–O) cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 2.56 (s, 3 H, Me), 3.36–3.40 (m, 2 H, CH2NH), 3.61 (s, 3 H, OMe), 3.70–3.74 (m, 1 H, CH2N), 4.23–4.027 (m, 1 H, CH2N), 5.06 (s, 1 H, CH12a), 7.07 (d, 3 J HH = 7.7 Hz, 1 H, CH4 of chromene), 7.08 (t, 3 J HH = 7.1 Hz, 1 H, CH2 of chromene), 7.23 (t, 3 J HH = 7.3 Hz, 1 H, CH3 of chromene), 7.37 (d, 3 J HH = 7.3 Hz, 1 H, CH1 of chromene), 8.16 (s, 1 H, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 21.92 (Me), 43.75 (CH2–NH), 50.26 (CH2–N), 56.90 (OMe), 66.10 (CH12a), 98.78 (C6a), 110.51 (C13), 122.04 (C13b of chromene), 123.01 (CH4 of chromene), 128.42 (CH2 of chromene), 132.76 (CH1 of chromene), 136.37 (CH3 of chromene), 137.20 (C13a of chromene), 157.15 (C4a of chromene), 165.77 (C7), 169.31 (COOMe), 172.23 (COO), 173.5 (CONH). MS (EI, 70 eV): m/z (%) = 340 [M+] (58), 325 (11), 282 (20), 281 (100), 212 (15), 211 (12), 210 (20), 155 (12), 140 (21), 139 (24), 128 (12), 127 (20), 126 (12), 115 (18), 77 (10), 70 (11), 63 (15), 59 (48), 56 (11), 44 (11), 43 (24), 42 (37), 41 (16). Anal. Calcd for C18H16N2O5 (340.33): C, 63.53; H, 4.74; N, 8.23. Found: C, 63.49; H, 4.75; N, 8.28. Methyl 7-Methyl-6,13-dioxo-9,10,11,12,13,13a-hexahydro-6H-chromeno[4′,3′:4,5]pyrido[1,2-a][1,4]diazepine-14-­carboxylate (8b) Yellow powder; yield: 0.230 g (65%); mp 245 °C (dec.). IR (KBr): 3424 and 3351 (NH), 1661 (C=O), 1611 (NCO), 1514 and 1455 (Ar), 1245 and 1099 (C–O) cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 1.77–1.93 (m, 2 H, CH2), 2.55 (s, 3 H, Me), 3.30–3.32 (m, 1 H, CH2N), 3.59–3.61 (m, 2 H, CH2NH), 3.60 (s, 3 H, OMe), 4.36–4.38 (m, 1 H, CH2N), 5.44 (s, 1 H, CH13a), 7.07 (d, 3 J HH = 7.7 Hz, 1 H, CH4 of chromene), 7.08 (t, 3 J HH = 7.1 Hz, 1 H, CH2 of chromene), 7.37 (t, 3 J HH = 7.3 Hz, 1 H, CH3 of chromene), 7.60 (d, 3 J HH = 7.3 Hz, 1 H, CH1 of chromene), 7.70 (s, 1 H, NH). 13C NMR (125 MHz, DMSO-d 6): δ = 17.08 (Me), 30.59 (CH2), 41.11 (CH2NH), 52.07 (OMe), 53.65 (CH2N), 62.71 (CH13a), 96.93 (C6a of chromene), 106.11 (C14), 117.03 (CH4 of chromene), 118.75 (C14b of chromene), 123.26 (CH2 of chromene), 129.81 (CH of chromene1), 131.56 (CH3 of chromene), 136.43 (C14a of chromene), 152.30 (C4a of chromene), 161.17 (C7), 162.90 (COOMe), 167.32 (COO), 171.93 (CONH). MS (EI, 70 eV): m/z (%) = 354 [M+] (3), 167 (11), 149 (53), 104 (13), 83 (15), 81 (10), 76 (10), 71 (26), 70 (24), 69 (28), 67 (12), 57 (93), 56 (20), 55 (57), 43 (100), 42 (18), 41 (92).Anal. Calcd for C19H18N2O5 (354.36): C, 64.40; H, 5.12; N, 7.91. Found: C, 66.50; H, 4.90; N, 6.92.