3.1.2. General Procedure for Sonogashira Cross-Coupling Reaction

A 25 mL oven-dried Schlenk tube was charged with 2 mol % of palladium (II) acetate (Pd(OAc)₂), 5 mol % of phosphine ligand (PPh₃) or PdCl₂(PPh₃)₂ (2–3 mol %), 3 mol % copper(I) iodide (CuI), and 1–2 mmol of chloro- or bromo-heterocyclic derivative under nitrogen (N₂) atmosphere, and the resultant mixture was dissolved in 5 mL of dry ACN or DMF. The reaction mixture was stirred for 5 min and supplied with 2 equiv. of 3,3′-diethoxy propyne and 5 equiv. of TEA or DIPEA. This was followed by stirring at 60 °C for 3–4 h. After consumption of the starting materials (monitored by TLC/TLC-MS), the solvent was removed under vacuum, and the residue was purified by column chromatography in hexane/EtOAc (10% to 30%) solvent system to afford the desired product.

The general procedure for Sonogashira coupling was applied using C (0.50 g, 1.64 mmol) yielding D as red oil in 62% (0.357 g, 1.017 mmol) yield. ¹H NMR (300 MHz, DMSO-d6) δ: 1.20 (t, J = 7.18 Hz, 6 H), 3.56–3.66 (m, 2 H), 3.66–3.79 (m, 2 H), 3.84 (s, 3 H), 5.60 (s, 1 H), 7.00–7.13 (m, 3 H), 7.99 (d, J = 8.69 Hz, 2 H), 8.33 (s, 1 H), 12.63 (br s, 1 H).

The general procedure for the Sonogashira reaction was applied using “X a” (1.94 g, 7.16 mmol), yielding the product as reddish-brown oil. The formation of “Y a” was confirmed by (+ve) APCI-MS m/z = 316.18 [M] calcd. for C₁₈H₂₄N₂O₃ [M], found: 317.22 m/z [M+H]. Without further purification, compound “Y a” was used in the next reaction.

Spectral data of the compound are in agreement with previous reports [48]. The general procedure for the Sonogashira reaction was applied using “X b” (1.00 g, 3.68 mmol) yielding the product as dark red liquid in 73% (0.85 g, 2.68 mmol) yield. ¹H NMR (300 MHz, CDCl₃) δ: 0.97–1.29 (m, 6 H), 2.67–2.71 (m, 2 H), 3.51–3.77 (m, 10 H), 5.40 (s, 1 H), 7.44 (d, J = 8.31 Hz, 1 H), 7.65 (dd, J = 7.74 Hz, 2.08 Hz, 1 H), 7.89 (s, 1 H); ¹³C NMR (75 MHz, CDCl3) δ: 14.4 (s, 1 C), 20.3 (s, 1 C), 30.7 (s, 1 C), 35.7 (s, 1 C), 37.9 (s, 1 C), 60.6 (s, 1 C), 66 (s, 1 C), 82.8 (s, 1 C), 85.1 (s, 1 C), 90.8 (s, 1 C), 126.4 (s, 1 C), 129.8 (s, 1 C), 134.7 (s, 1 C), 142.7 (s, 1 C), 147.6 (s, 1 C), 161.8 (s, 1 C), 166.4 (s, 1 C); (+ve) APCI-MS m/z = 318.16 [M] calcd. for C₁₇H₂₂N₂O₄ [M], found: 319.16 m/z [M+H].

The spectral data of compound “Y c” are in agreement with the literature [48]. The general procedure for the Sonogashira reaction was applied using “X c” (1.00 g, 3.89 mmol) yielding the product as reddish oil in 78% (0.923 g, 3.03 mmol) yield. ¹H NMR (300 MHz, CDCl₃) δ: 1.14 (t, J = 6.99 Hz, 12 H), 3.13 (br s, 2 H), 3.43 (br s, 2 H), 3.49–3.61 (m, 2 H), 3.64–3.76 (m, 2 H), 5.38 (s, 1 H), 7.38–7.43 (m, 1 H), 7.58 (dd, J = 8.12 Hz, 2.08 Hz, 1 H), 8.47 (s, 1 H); ¹³C NMR (75 MHz, CDCl3) δ: 14.7 (s, 1 C), 20.6 (s, 1 C), 31 (s, 1 C), 36.1 (s, 1 C), 39.3 (s, 1 C), 43.1 (s, 1 C), 60.9 (s, 1 C), 83.3 (s, 1 C), 85 (s, 1 C), 91.2 (s, 1 C), 126.7 (s, 1 C), 132 (s, 1 C), 134.2 (s, 1 C), 142.4 (s, 1 C), 147.2 (s, 1 C), 162.1 (s, 1 C), 167.5 (s, 1 C); (+ve) APCI-MS m/z = 304.18 [M] calcd. for C₁₇H₂₄N₂O₃ [M], found: 305 m/z [M+H].

The general procedure for the Sonogashira coupling was applied using “X d” (0.39 g, 1.00 mmol), yielding the product as a red oil. The formation of “Y d” was confirmed by (+ve) APCI-MS m/z = 439.48 m/z [M] calcd. for C₂₄H₂₆FN₃O₄ [M], found: 440.1 m/z [M+H]. The product was used further without additional purification.

The general procedure for the Sonogashira reaction was applied using “X e” (0.425 g, 1.00 mmol), yielding the product as a red liquid. The formation of “Y e” was confirmed by (+ve) APCI-MS m/z = 471.18 m/z [M] calcd. for C₂₄H₂₉N₃O₅S [M], found: 472.1 m/z [M+H]. The product was used further without additional purification.