An Efficient Approach to the Synthesis of Alkyl 7-Hydroxy-1-oxo-1,2,3,4-
tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylates via a One-Pot, Three-Component Reaction

Abdolali Alizadeh; Marziyeh Hossein Abadi; Rashid Ghanbaripour

doi:10.1055/s-0034-1378275

Synlett, Table of Contents

Synlett 2014; 25(12): 1705-1708
DOI: 10.1055/s-0034-1378275

letter

An Efficient Approach to the Synthesis of Alkyl 7-Hydroxy-1-oxo-1,2,3,4- tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylates via a One-Pot, Three-Component Reaction

Authors

Abdolali Alizadeh*

Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Fax: +98(21)88006544 Email: abdol_alizad@yahoo.com Email: aalizadeh@modares.ac.ir
Marziyeh Hossein Abadi

Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Fax: +98(21)88006544 Email: abdol_alizad@yahoo.com Email: aalizadeh@modares.ac.ir
Rashid Ghanbaripour

Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Fax: +98(21)88006544 Email: abdol_alizad@yahoo.com Email: aalizadeh@modares.ac.ir

Abstract

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Abstract

An efficient synthesis of alkyl 7-hydroxy-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylate derivatives by reaction between diamines, dialkyl acetylenedicarboxylates, and alkyl or aryl glyoxales is reported. Ease of handling, easy purification, and good yields are the main advantages of the presented method.

Key words

diamine - dialkyl acetylenedicarboxylate - glyoxale - alkyl 7-hydroxy-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylate - one-pot, three-component reaction

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References

References and Notes

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21 To a solution of ethylenediamine (1 mmol) in EtOH (2 mL), dimethyl acetylenedicarboxylate (1 mmol) was added dropwise at r.t. After 30 min, methylglyoxal (1 mmol) and PTSA (0.1 mmol) were added to the reaction mixture, and the solution was stirred for 2.5 h at reflux conditions. Upon completion (3 h), monitored by TLC, the solvent was cooled at an ice bath, and the precipitate was filtered to afford the pure products 3a–f. Methyl 7-Hydroxy-6-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazine-8-carboxylate (3a) Pale orange powder; 0.156 g, 70% yield; mp 187–189 °C. IR (KBr): 3211 (NH), 3099 (OH), 1715 (CO₂Me), 1675 (NCO), 1219 and 1146 (CO) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.20 (s, 3 H, CH₃), 3.65–3.68 (m, 2 H, CH₂NH), 3.94 (s, 3 H, OMe), 3.95 (t, ³ J _HH = 5.6 Hz, 2 H, CH₂N), 7.28 (s, 1 H, NH), 8.39 (s, 1 H, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 7.9 (CH₃), 39.3 (CH₂NH), 41.6 (CH₂N), 52.1 (OMe), 103.4 (C⁶), 114.4 (C⁸), 118.2 (C^8a), 145.9 (COH), 159.3 (CO₂CH₃), 167.5 (NCO). MS: m/z = 225 [M⁺ + 1], 224 [M⁺], 192, 164, 136, 123, 107, 95, 79, 66, 53. Anal. Calcd (%) for C₁₀H₁₂N₂O₄: C, 53.57; H, 5.39; N, 12.40. Found: C, 53.51; H, 5.46; N, 12.38. Ethyl 7-Hydroxy-6-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazine-8-carboxylate (3b) Pale brown powder; 0.178 g, 74%; mp 178–179 °C. IR (KBr): 3393 (NH), 3193 (OH), 1710 (CO₂Et), 1668 (NCO), 1335, 1225 and 1150 (CO) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.34 (t, ³ J _HH = 7.0 Hz, 3 H, CH₂CH ₃), 2.12 (s, 3 H, CH₃), 3.56–3.59 (m, 2 H, CH₂NH), 3.87 (t, ³ J _HH = 5.7 Hz, 2 H, CH₂N), 4.32 (q, ³ J _HH = 7.0 Hz, 2 H, CH ₂CH₃), 7.01 (s, 1 H, NH), 8.28 (s, 1 H, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 7.9 (CH₃), 14.2 (CH₃), 39.3 (CH₂NH), 41.6 (CH₂N), 60.9 (OCH₂), 103.9 (C⁶), 114.3 (C⁸), 118.3 (C^8a), 145.8 (COH), 159.2 (CO₂Et), 166.9 (NCO). MS: m/z = 239 [M⁺ + 1], 238 [M⁺], 192, 164, 136, 123, 107, 95, 80, 67, 53. Anal. Calcd (%) for C₁₁H₁₄N₂O₄: C, 55.46; H, 5.92; N, 11.76. Found: C, 55.36; H, 5.87; N, 11.82. Methyl 7-Hydroxy-1-oxo-6-1,2,3,4-tetrahydrophenyl-pyrrolo[1,2-a]pyrazine-8-carboxylate (3c) Pale yellow powder; 0.238 g, 83% yield; mp 90–92 °C. IR (KBr): 3350 (NH), 3235 (OH), 1706 (CO₂Me), 1664 (NCO), 1580 and 1481 (Ar), 1348, 1225 and 1141 (CO) cm^–1. ¹H NMR (300.13 MHz, CDCl₃): δ = 3.69–3.65 (m, 2 H, CH₂NH), 3.98 (s, 3 H, OMe), 4.11 (t, ³ J _HH = 5.9 Hz, 2 H, CH₂N), 6.59 (s, 1 H, NH), 7.35–7.39 (m, 1 H, CH _para of Ph), 7.44–7.50 (m, 4 H, 2 × CH _ortho and 2 × CH _meta of Ph), 8.80 (s, 1 H, OH). ¹³C NMR (75 MHz, CDCl₃): δ = 39. 7 (CH₂NH), 43.1 (CH₂N), 52.2 (OMe), 103.7 (C⁶), 118.7 (C⁸), 119.6 (C^8a), 128.0 (CH _para of Ph), 128.3 (C _ipso ), 128.7 (2 × CH _ortho of Ph), 129.4 (2 × CH _meta of Ph), 146.6 (COH), 158.9 (CO₂Me), 167.6 (NCO). MS: m/z = 287 [M⁺ + 1], 287 [M⁺], 279, 262, 254, 219, 205, 167, 149, 132, 121, 113, 104, 93, 83, 71, 57. Anal. Calcd (%) for C₁₅H₁₄N₂O₄: C, 62.93; H, 4.93, N, 9.79. Found: C, 62.97; H, 5.01; N, 9.86. Ethyl 7-Hydroxy-1-oxo-6-1,2,3,4-tetrahydrophenyl-pyrrolo[1,2-a]pyrazine-8-carboxylate (3d) Pale yellow powder; 0.198 g 66% yield; mp 213–214 °C. IR (KBr): 3184 (NH), 3064 (OH), 1708 (CO₂Et), 1665 (NCO), 1580 and 1481 (Ar), 1300, 1239 and 1197 (CO) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.45 (t, ³J _HH = 7.2 Hz, 3H, CH₂CH ₃), 3.10–3.64 (m, 2 H, CH₂NH), 4.11 (t, ³ J _HH = 5.6 Hz, 2 H, CH₂N), 4.45 (q, ³J _HH = 7.2 Hz, 2 H, CH ₂CH₃), 7.12 (s, 1 H, NH), 7.36–7.40 (m, 1 H, CH _para of Ph), 7.46–7.51 (m, 4 H, 2 × CH _ortho and 2 × CH _meta of Ph), 8.75 (s, 1 H, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2 (CH₃), 39.6 (CH₂NH), 43.1 (CH₂N), 61.1 (OCH₂), 104.1 (C⁶), 118.6 (C⁸), 119.8 (C^8a), 127.9 (CH _para of Ph), 128.4 (C _ipso ), 128.7 (2 × CH _ortho of Ph), 129.4 (2 × CH _meta of Ph), 146.4 (COH), 159.2 (CO₂Et), 166.9 (NCO). MS: m/z = 301 [M⁺ + 1], 300 [M⁺], 254, 225, 211, 198, 183, 169, 155, 141, 128, 115, 104, 95, 77, 67, 53. Anal. Calcd (%) for C₁₆H₁₆N₂O₄: C, 63.99; H, 5.37, N, 9.33. Found: C, 64.01; H, 5.49; N, 9.30. Methyl 7-Hydroxy-1-oxo-6-(4-chlorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylate (3e) Pale beige powder; 0.245 g, 86% yield; mp 203–204 °C. IR (KBr): 3325 (NH), 3200 (OH), 1710 (CO₂Me), 1660 (NCO), 1574 and 1481 (Ar), 1299, 1233 and 1138 (C–O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.63–3.68 (m, 2 H, CH₂NH), 3.99 (s, 3 H, OMe), 4.10 (t, ³ J _HH = 5.8 Hz, 2 H, CH₂N), 6.84 (s, 1 H, NH), 7.41 (d, ³ J _HH = 8.8 Hz, 2 H, 2 × CH of Ar), 7.46 (d, ³ J _HH = 8.4 Hz, 2 H, 2 × CH of Ar), 8.85 (s, 1 H, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 39.6 (CH₂NH), 43.1 (CH₂N), 52.3 (OMe), 103.7 (C⁶), 117.5 (C⁸), 120.0 (C^8a), 126.7 (C _ipso ), 129.0 (2 × CH of Ar), 130.7 (2 × CH of Ar), 133.9 (C _ipso Cl), 146.8 (COH), 158.9 (CO₂Me), 167.5 (NCO). MS: m/z = 322 [M⁺ + 2], 321 [M⁺ + 1], 320 [M⁺], 288, 262, 253, 232, 189, 175, 162, 151, 137, 123, 111, 95, 80, 67, 53. Anal. Calcd (%) for C₁₅H₁₃ClN₂O₄: C, 66.02; H, 5.30; N, 13.39. Found: C, 65.98; H, 5.45; N, 13.43. Ethyl 7-Hydroxy-1-oxo-6-(4-chlorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylate (3f) Yellow powder; 0.223 g, 66% yield; mp 243–244 °C. IR (KBr): 3181 (NH), 3073 (OH), 1713 (CO₂Et), 1677 (NCO), 1566 and 1476 (Ar), 1302, 1224 and 1150 (CO) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.45 (t, ³ J _HH = 7.0 Hz, 3 H, CH₂CH ₃), 3.63–3.68 (m, 2 H, CH₂NH), 4.10 (t, ³ J _HH = 5.8 Hz, 2 H, CH₂N), 4.46 (q, ³ J _HH = 7.0 Hz, 2 H, CH ₂CH₃), 6.51 (s, 1 H, NH), 7.41 (d, ³ J _HH = 8.8 Hz, 2 H, 2 × CH of Ar), 7.46 (d, ³ J _HH = 8.8 Hz, 2 H, 2 × CH of Ar), 8.84 (s, 1 H, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2 (CH₃), 39.7 (CH₂NH), 43.1 (CH₂N), 61.3 (OCH₂), 104.2 (C⁶), 117.4 (C⁸), 120.1 (C^8a), 126.8 (C _ipso ), 129.0 (2 × CH of Ar), 130.5 (2 × CH of Ar), 133.9 (C _ipso Cl), 146.7 (COH), 158.7 (CO₂Et), 166.9 (NCO). MS: m/z = 336 [M⁺ + 2], 335 [M⁺ + 1], 334 [M⁺], 288, 259, 245, 232, 203, 189, 175, 162, 138, 123, 111, 95, 80, 67, 53. Anal. Calcd (%) for C₁₆H₁₅ClN₂O₄: C, 57.41; H, 4.52; N, 8.37. Found: C, 57.32; H, 4.47; N, 8.31.