The First Example of Azole-Fused Cyclic Anhydride Reacting in the Castagnoli–Cushman Way

^◊ On research training leave from National Polytechnic Institute of Industrial and Chemical Engineering, Toulouse, France.

Abstract

Pyrazole-fused cyclic anhydrides have been employed for the first time as the Castagnoli–Cushman reaction partners to produce hitherto unknown 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-7-carboxylates in remarkably convenient and speedy fashion. Attempts to realize the same chemistry with indole and benzimidazole analogues failed.

Key words

multicomponent reactions - Castagnoli–Cushman reaction - nonstabilized enolate - pyrazole-fused - cyclic anhydrides

• References and Notes

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• 8 General Procedure for the Synthesis of Compounds 13a–n A mixture of anhydride 12 (0.5 mmol) and the corresponding imine (0.52 mmol) in dry chlorobenzene (2 mL) was stirred in a screw-cap vial at 130 °C for 16 h. Upon cooling to r.t. the solvent was removed in vacuo, and the residue was dissolved in acetone (10 mL). To the solution were added K₂CO₃ (1 mmol) and MeI (1 mmol), and the mixture was vigorously stirred at r.t. for 20 h. The solution was separated from solids, evaporated, and the resulting residue was subjected to column chromatography on silica gel.
• 9 Characterization Data of Representative Compounds Compound 13a: colorless amorphous solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.68 (d, J = 8.2 Hz, 2 H), 7.23 (s, 1 H), 7.21 (d, J = 7.9 Hz, 2 H), 7.13 (d, J = 8.1 Hz, 2 H), 7.06 (d, J = 8.2 Hz, 2 H), 5.28 (s, 1 H), 5.26 (d, J = 1.4 Hz, 1 H), 4.22 (dq, J = 14.4, 7.2 Hz, 1 H), 3.79 (s, 3 H), 2.89 (dq, J = 14.2, 7.1 Hz, 1 H), 2.37 (s, 3 H), 2.31 (s, 3 H), 1.17 (t, J = 7.2 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 168.5, 157.1, 153.0, 138.8, 138.2, 135.7, 133.7, 129.9, 129.4, 129.4, 126.0, 125.6, 104.7, 65.3, 61.7, 53.5, 40.1, 21.3, 21.0, 13.1. HRMS: m/z [M + H]⁺ calcd for C₂₄H₂₆N₃O₃: 404.1969; found: 404.1986. Compound 13i: colorless viscous oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.36 (dd, J = 3.6, 1.1 Hz, 1 H), 7.25 (dd, J = 5.1, 1.1 Hz, 1 H), 7.15 (s, 1 H), 7.12 (d, J = 8.1 Hz, 2 H), 7.08–7.01 (m, 3 H), 5.27 (s, 1 H), 5.25 (d, J = 1.4 Hz, 1 H), 4.21 (dq, J = 14.4, 7.2 Hz, 1 H), 3.78 (s, 3 H), 2.87 (dq, J = 14.2, 7.1 Hz, 1 H), 2.29 (s, 3 H), 1.15 (t, J = 7.2 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 168.3, 156.8, 148.2, 138.8, 135.9, 135.2, 133.5, 129.9, 127.5, 125.9, 125.2, 124.7, 104.7, 65.2, 61.7, 53.5, 40.1, 21.0, 13.1. HRMS: m/z [M + H]⁺ calcd for C₂₁H₂₂N₃O₃S: 396.1376; found: 396.1379; Compound 13l: colorless viscous oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.13 (d, J = 7.9 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 2 H), 6.82 (s, 1 H), 5.20 (s, 1 H), 5.18 (s, 1 H), 4.13 (dt, J = 13.8, 7.9 Hz, 1 H), 3.77 (s, 3 H), 2.67 (ddd, J = 13.5, 8.2, 5.3 Hz, 1 H), 2.32 (s, 3 H), 1.65–1.46 (m, 2 H), 1.29 (s, 9 H), 0.89 (t, J = 7.4 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 168.8, 163.8, 157.7, 138.6, 134.9, 133.9, 129.8, 126.1, 104.7, 64.8, 61.9, 53.3, 46.5, 32.2, 30.4, 21.2, 21.0, 11.0. HRMS: m/z [M + H]⁺ calcd for C₂₂H₃₀N₃O₃: 384.2282; found: 384.2293.
• 10 Kantin G. Chupakhin E. Dar’in D. Krasavin M. Tetrahedron Lett. 2017; 58: 3160