Efficient One-pot Synthesis of 1H-Pyrazolo[1,5-b]indazoles by a Domino Staudinger–Aza-Wittig Cyclization

Abstract

1H-Pyrazolo[1,5-b]indazoles were prepared via a domino Staudinger–aza-Wittig cyclization in one-pot fashion, starting from easily accessible azides and triphenylphosphine.

Key words

1H-pyrazolo[1,5-b]indazole - domino reaction - aza-Wittig reaction - azide - iminophosphorane

• References and Notes

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• 12 General Procedure for the Preparation of Azides 5 To a mixture of piperidine (0.85 g, 10 mmol) and AcOH (0.6 g, 10 mmol) in EtOH (10 mL) at 0 °C was added 2-azidobenzaldehyde (1.32 g, 10 mmol) and ketone (10 mmol). After stirring for 1–2 h, the solvent was evaporated under vacuum, and the residue was recrystallized to give the azide 5. Compound 5a: light yellow solid (yield 89%), mp 75–76 °C. ¹H NMR (600 MHz, CDCl₃): δ = 7.80 (s, 1 H, =CH), 7.46–7.11 (m, 4 H, ArH), 4.30–4.25 (m, 2 H, OCH₂), 2.45 (s, 3 H, CH₃), 1.24–1.20 (m, 3 H, CH₃) ppm. ¹³C NMR (150 MHz, CDCl₃): d = 194.7, 167.1, 139.3, 136.2, 135.5, 131.6, 128.9, 124.6, 118.3, 61.5, 26.4, 13.7 ppm. MS (EI, 70 eV): m/z (%) = 259 (4) [M⁺], 231 (12), 217 (19), 203 (27), 143 (100), 115 (58). Anal. Calcd for C₁₃H₁₃N₃O₃: C, 60.22; H, 5.05; N, 16.21. Found: C, 60.01; H, 4.92; N, 16.02.
• 13 General Procedure for the Preparation of 9 To a solution of azide 5 (2 mmol) in dry toluene (10 mL) was added dropwise a solution of Ph₃P (0.52 g, 2 mmol) in toluene (10 mL) at 0 °C. The reaction mixture was stirred for 2 h and then was refluxed for 2–8 h. The mixture was condensed, and the precipitate was collected or the residue was chromatographed (PE–Et₂O, 4:1) on a silica gel column to give 1H-pyrazolo[1,5-b]indazole derivatives 9. Compound 9a: white solid (yield 90%); mp 193–194 °C. ¹H NMR (600 MHz, CDCl₃): δ = 12.0 (s, 1 H, NH), 8.27 (d, J = 7.8 Hz, 2 H, ArH), 7.54–7.32 (m, 4 H, ArH), 4.45 (q, J = 7.2 Hz, 2 H, OCH₂), 2.67 (s, 3 H, CH₃), 1.50 (t, J = 7.2 Hz, 3 H, CH₃) ppm. ¹³C NMR (150 MHz, CDCl₃): δ = 164.0, 152.7, 143.4, 135.5, 128.4, 123.0, 122.4, 116.2, 110.8, 100.2, 59.9, 14.8, 14.3 ppm. MS (EI, 70 eV): m/z (%) = 243 (39) [M⁺], 198 (10), 144 (100). Anal. Calcd for C₁₃H₁₃N₃O₂: C, 64.19; H, 5.39; N, 17.27. Found: C, 63.89; H, 5.22; N, 17.32.
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