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; Parinaz Jamal

doi:10.1055/s-0036-1591550

Synlett, Table of Contents

Synlett 2018; 29(08): 1107-1111
DOI: 10.1055/s-0036-1591550

letter

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

Authors

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

Abstract

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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

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References

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 (C^4a), 125.1 (CH⁶), 126.9 (CH⁷), 128.3 (CH⁵), 133.8 (C² of butenedioate), 141.3 (CH³ of butenedioate), 152.3 (C^8a), 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): M_W = 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 (C^4a), 128.8 (CH⁷), 129.0 (CH⁵), 136.5 (C² of butenedioate), 140.8 (CH³ of butenedioate), 151.0 (C^8a), 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, CH^12a), 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 (CH^12a), 98.78 (C^6a), 110.51 (C¹³), 122.04 (C^13b of chromene), 123.01 (CH⁴ of chromene), 128.42 (CH² of chromene), 132.76 (CH¹ of chromene), 136.37 (CH³ of chromene), 137.20 (C^13a of chromene), 157.15 (C^4a 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, CH^13a), 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 (CH^13a), 96.93 (C^6a of chromene), 106.11 (C¹⁴), 117.03 (CH⁴ of chromene), 118.75 (C^14b of chromene), 123.26 (CH² of chromene), 129.81 (CH of chromene¹), 131.56 (CH³ of chromene), 136.43 (C^14a of chromene), 152.30 (C^4a 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.

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