by Suzuki and Sonogashira cross-coupling reactions ... · 1 Regiocontrolled functionalization of 2,3-dihalogenoimidazo[1,2-a]pyridines by Suzuki and Sonogashira cross-coupling reactions

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Regiocontrolled functionalization of 2,3-dihalogenoimidazo[1,2-a]pyridines by Suzuki and Sonogashira cross-coupling reactions

P.-O. Delaye,a M. Pénichon,a H. Allouchi,a C. Enguehard-Gueiffierb and A. Gueiffierb

a) UMR INRA 1282 Infectiologie et Santé Publique, Recherche et Innovation en Chimie Médicinale, Université François Rabelais, 31 avenue Monge, 37200 Tours, France.

b) UMR INSERM 1069 Nutrition, Croissance et cancer, Université François Rabelais, 31 avenue Monge, 37200 Tours, France.

SUPPORTING INFORMATIONS

1) Generals considerations2) Characterization data for products

3) Copies of NMR spectra for products

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2017

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General considerationsAll reagents were used directly as obtained commercially. Thin-layer chromatography (TLC) were performed using Merk® silica gel 60F254 plates. Column chromatography were preformed using Merck Geduran® Si 60 (40-63µm) silica. Melting points were determined on a capillary apparatus (Stuart, Staffordshire, United Kingdom) and are uncorrected. Microwave heating was performed using CEM® Explorer SP 12 S class apparatus (max power 300W). NMR experiments were performed at 300 mHz (1H) and 75 mHz (13C) on a Bruker-Avance 300 MHz spectrometer. Assignment of carbons noted C* may be interchanged. Mass spectra were determined on a Hewlett Packard 5988A spectrometer or on a Shimadzu QP 2010 spectrometer by direct inlet at 70 eV. NMR data for compounds 2a1, 2b2, 3a3, 3b4, 3d5, 3f4 and 6a6 were previously described in literature.

2,3-diodoimidazo[1,2-a]pyridine (1a)To a stirred solution of 2-iodoimidazo[1,2-a]pyridine (1.22g, 5mmol, 1eq) in CH3CN (20mL) was

added NIS (1.24g, 5.5mmol, 1.1eq) in one portion at room temperature. A white solid precipitated quickly. After 3h at room temperature the reaction was quenched with 30mL of water and extracted thrice with 30mL of CH2Cl2. The combined organic phases were washed with 50mL of Na2S2O3 aqueous saturated solution, dried on Na2SO4 and evaporated to dryness. The pale yellow solid obtained (1.7g, 4,6mmol, yield: 92%) is used without further purification. 1H NMR (CDCl3) δ: 8.03 (d, 1H, J = 9Hz, H-5), 7.54 (d, 1H, J = 9Hz, H-8), 7.20 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.0Hz H-7), 6.89 (td, 1H, J = 9.0Hz, 0.6Hz, H-6). 13C NMR (CDCl3) δ: 149.4 (C-8a), 127.0 (C-5), 125.7 (C-7), 117.2 (C-8), 113.9 (C-6), 104.6 (C-2), 73.0 (C-3). m.p.: 114-118°C.HRMS (ESI): m/z calculated for C7H4I2N2 [M+H]+ : 370.85366, found: 370.85389.

2-iodo-3-bromoimidazo[1,2-a]pyridine (1b)To a stirred solution of 2-iodoimidazo[1,2-a]pyridine (1.75g, 7.2mmol, 1eq) in CH3CN (30mL) was

added NBS (1.4g, 7.9mmol, 1.1eq) in one portion at room temperature. A white solid precipitated quickly. After 3h at room temperature the reaction was quenched with 30mL of water and extract thrice with 30mL of CH2Cl2. The combined organic phases were washed with 50mL of Na2S2O3 aqueous saturated solution, dried on Na2SO4 and evaporated to dryness. The crude mixture was purified by column chromatography (silica, eluent: CH2Cl2). 1b is obtained as a gray solid (2.1g, 6.5mmol, yield: 90%). 1H NMR (CDCl3) δ: 8.06 (dt, 1H, J = 6.9Hz, 0.9Hz, H-5), 7.56 (dt, 1H, J = 9.3Hz, 0.9Hz, H-8), 7.21 (ddd, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 6.91 (td, 1H, J = 6.9Hz, 0.9Hz, H-6). 13C NMR (CDCl3) δ: 147.4 (C-8a), 125.3 (C-7), 124.3 (C-5), 117.3 (C-8), 113.7 (C-6), 101.9 (C-2*), 95.9 (C-3*). m.p.: 114-118°C. HRMS (ESI): m/z calculated for C7H4BrIN2 [M+H]+ : 322.86753, found: 322.86793.

General procedure for Suzuki coupling at C-2 position or C-3 position.1b (646mg, 2mmol, 1eq) or 2b-d (n mmol, 1 eq for C-3 functionalization), Pd(PPh3)4 (116mg,

0.1mmol, 5%), Na2CO3 (424mg, 4mmol, 2eq) and boronic acid (2.2mmol, 1.1eq) were introduced into a microwave tube. The tube was sealed with a rubber septum and then evacuated and refilled with argon thrice. 1,4-Dioxane (8mL) and water (4mL) were then added. The reaction mixture was heated under microwave iradiation at 120°C for 1h. After cooling, the reaction mixture was partitioned between EtOAc (10mL) and water (10mL). The aqueous phase was extracted twice with EtOAc (10mL). Organic phases were combined, dried over MgSO4 and evaporated to dryness. The crude mixture was purified by column chromatography (silica, eluent: mixture of CH2Cl2 and EtOAc).

3-bromo-2-(thiophen-3-yl)imidazo[1,2-a]pyridine (2c)

1 Gao, Y.; Yin, M.; Wu, W.; Huang, H.; Jiang, H. Adv. Synth. Catal. 2013, 355, 2263-2273.2 Zhou, X.; Yan, H.; Ma, C.; He, Y.; Li, Y.; Cao, J.; Yan, R.; Huang, G. J. Org. Chem. 2016, 81, 25-31.3 Hiebel, M.-A.; Fall, Y.; Scherrmann, M.-C.; Berteina-Raboin, S. Eur. J. Org. Chem. 2014, 4646-4650.4 Marhadour, S.; Marchand, P.; Pagniez, F.; Bazin, M.-A.; Picot, C.; Lozach, O.; Ruchaud, S.; Antoine, M.; Meijer, L.; Rachidi, N.; Le Pape, P. Eur. J. Med. Chem. 2012, 58, 543-556.5 Enguehard, C.; Renou, J.-L.; Collot, V.; Hervet, M.; Rault, S.; Gueiffier, A. J. Org. Chem. 2000, 65, 6572-6575. 6 Meng, X.; Yu, C.; Chen, G.; Zhao, P. Catal. Sci. Technol. 2015, 5, 372-379.

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Eluent: CH2Cl2/EtOAc 98/297/3. Pale yellow solid, yield: 80%. 1H NMR (CDCl3) δ: 8.04 (m, 2H, H-5, thienyl-2), 7.86 (dd, 1H, J = 4.8Hz, 1.2Hz, thienyl-4), 7.56 (dt, 1H, J = 9.0Hz, 0.9Hz, H-8), 7.39 (dd, 1H, J = 4.8Hz, 3.0Hz, thienyl-5), 7.18 (ddd, 1H, J = 9.0Hz, 6.6Hz, 1.2Hz, H-7), 6.84 (td, 1H, J = 6.9Hz, 0.9Hz, H-6). 13C NMR (CDCl3) δ: 145.2 (C-8-a), 139.1 (C-2), 133.9 (thienyl-3), 127.0 (thienyl-4), 125.8 (thienyl-5), 125.6 (C-7), 124.0 (C-5), 123.8 (thienyl-2), 117.4 (C-8), 113.4 (C-6), 91.5 (C-3). m.p.: 130-134°C. HRMS (ESI): m/z calculated for C11H7BrN2S [M+H]+ : 278.95861, found: 278.95892.

3-bromo-2-methylimidazo[1,2-a]pyridine (2d)Eluent: CH2Cl2/EtOAc 90/1080/20. Yellow solid, yield: 42%. 1H NMR (CDCl3) δ: 7.99 (dt, 1H,

J = 6.9Hz, 0.9Hz, H-5), 7.48 (dt, 1H, J = 9.0Hz, 0.9Hz, H-8), 7.15 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 6.84 (td, 1H, J = 6.9Hz, 0.9Hz, H-6), 2.43 (s, 3H, CH3). 13C NMR (CDCl3) δ: 145.2 (C-8a), 142.0 (C-2), 124.4 (C-7), 123.7 (C-5), 117.0 (C-8), 112.6 (C-6), 93.0 (C-3), 13.7 (CH3). m.p.: 45-49°C. HRMS (ESI): m/z calculated for C8H7BrN2 [M+H]+ : 210.98654, found: 210.98671.

3-(furan-2-yl)-2-phenylimidazo[1,2-a]pyridine (3c)Eluent: CH2Cl2/EtOAc 95/5. Brown solid, yield: 67%. 1H NMR (CDCl3) δ: 8.19 (dt, 1H, J = 6.9Hz,

0.9Hz, H-5), 7.77-7.74 (m, 2H, Ph-2,6), 7.66 (dt, 1H, J = 9.0Hz, 0.9Hz, H-8), 7.63 (t, 1H, J = 1.2Hz, furyl-5), 7.40-7.31 (m, 3H, Ph-3,4,5), 7.22 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 6.80 (td, 1H, J = 6.9Hz, 1.2Hz, H-6), 6.56 (m, 2H, furyl-3,4). 13C NMR (CDCl3) δ: 145.5 (C-8a), 145.3 (furyl-2), 143.6 (C-2), 143.4 (furyl-5), 134.0 (Ph-1), 128.5 (Ph-3,5*), 128.2 (Ph-2,6*), 128.1 (Ph-4), 125.5 (C-7), 124.8 (C-5), 117.6 (C-8), 112.8 (C-6), 111.8 (furyl-3*), 111.6 (furyl-4*). m.p.: 111-115°C. HRMS (ESI): m/z calculated for C17H12N2O [M+H]+ : 261.10224, found: 261.10229.

3-phenyl-2-(thiophen-3-yl)imidazo[1,2-a]pyridine (3e)Eluent: CH2Cl2/EtOAc 100/093/7. white solid, yield: 88%. 1H NMR (CDCl3) δ: 7.91 (dt, 1H J =

6.9Hz, 1.2Hz, H-5), 7.78 (d, 1H, J = 9.3Hz, H-8), 7.65 (dd, 1H, J = 3.0Hz, 1.5Hz, thienyl-2), 7.61-7.48 (m, 5H, Ph-2,3,4,5,6), 7.31-7.21 (m, 3H, H-7, thienyl-4,5), 6.80 (td, 1H, J = 6.9Hz, 1.2Hz, H-6). 13C NMR (CDCl3) δ: 143.9 (C-8a), 137.5 (C-2), 134.2 (thienyl-3), 131.1 (Ph-3,5*), 129.8 (Ph-2,6*), 129.7 (Ph-4), 129.0 (Ph-1), 127.0 (thienyl-2), 126.0 (C-7), 125.6 (thienyl-4*), 123.62 (C-5*), 123.59 (thienyl-5*), 120.6 (C-3), 116.9 (C-8), 113.2 (C-6). m.p.: 148-152°C. HRMS (ESI): m/z calculated for C17H12N2S [M+H]+ : 277.07940, found: 277.07945.

2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (3f)4

1b (200mg, 0.619mmol, 1eq), Pd(PPh3)4 (36mg, 0.031mmol, 5%), Na2CO3 (131mg, 1.24mmol, 2eq) and phenylboronic acid (83mg, 0.681mmol, 1.1eq) were introduced into a microwave tube. The tube was sealed with a rubber septum and then evacuated and refilled with argon thrice. 1,4-Dioxane (2.8mL) and water (1.4mL) were then added. The reaction mixture was heated under microwave irradiation at 120°C for 1h. After cooling, 4-pyridylboronic acid (98mg, 0.681mmol, 1.1eq) was added and the reaction was heated again under microwave irradiation at 120°C for 1h. After cooling, the reaction mixture was partitioned between CH2Cl2 (10mL) and water (10mL). The aqueous phase was extracted twice with CH2Cl2 (10mL). Organic phases were combined, dried over MgSO4 and evaporated to dryness. The crude mixture was purified by column chromatography (silica, eluent: CH2Cl2/EtOAc 100/093/7) to afford 3a as a white solid (106mg), yield: 73%.

General procedure for Sonogashira coupling at C-2 position.1b (161mg, 0.5mmol, 1eq), PdCl2(PPh3)2 (35mg, 0.05mmol, 10%) and CuI (10mg, 0.05mmol, 10%)

were introduced into a screw-cap test tube. The tube was sealed with a rubber septum and then evacuated and refilled with argon thrice. DMF (2mL), Et3N (278µL, 2mmol, 4eq) and alkyne (0.55mmol, 1.1eq) were then added. The reaction mixture was stirred for 30 minutes at room temperature. The reaction mixture was partitioned between CH2Cl2 (10mL) and brine (10mL). The aqueous phase was extracted twice with CH2Cl2 (10mL). Organic phases were combined, dried over MgSO4 and evaporated to dryness. The crude mixture was purified by column chromatography (silica, eluent: mixture of petroleum ether and diethylether).

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3-bromo-2-(phenylethynyl)imidazo[1,2-a]pyridine (4a)Eluent: PE/Et2O 50/50. Orange solid, yield: 95%. 1H NMR (CDCl3) δ: 8.08 (dt, 1H, J = 6.9Hz,

0.9Hz, H-5), 7.64-7.61 (m, 3H, 2CH Ph, H-8), 7.38-7.36 (m, 3H, 3CH Ph), 7.31 (ddd, 1H, J = 9.0Hz, 6.6Hz, 1.2Hz, H-7), 6.98 (td, 1H, J = 6.9Hz, 1.2Hz, H-6). 13C NMR (CDCl3) δ: 145.1 (C-8a), 132.0 (2CH Ph), 129.0 (CH Ph), 128.5 (2CH Ph), 128.4 (C-2), 126.2 (C-7), 124.1 (C-5), 122.5 (Cq Ph), 117.7 (C-8), 114.1 (C-6), 99.4 (C-3), 94.6 (CC-Ph), 81.0 (CC-Ph). m.p.: 117-121°C. HRMS (ESI): m/z calculated for C15H9BrN2 [M+H]+ : 297.00219, found: 297.00257.

3-bromo-2-(cyclopropylethynyl)imidazo[1,2-a]pyridine (4b)Eluent: PE/Et2O 50/50. Yellow solid, yield: 98%. 1H NMR (CDCl3) δ: 7.96 (dt, 1H, J = 6.9Hz,

0.9Hz, H-5), 7.47 (dt, 1H, J = 9.3Hz, 0.9Hz, H-8), 7.19 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 6.87 (td, 1H, J = 6.9Hz, 0.9Hz, H-6), 1.50 (quint, 1H, CH c-Pr), 0.88 (m, 4H, 2CH2 c-Pr). 13C NMR (CDCl3) δ: 144.9 (C-8a), 129.1 (C-2), 125.5 (C-7), 123.8 (C-5), 117.5 (C-8), 113.6 (C-6), 98.9 (CC-c-Pr), 98.4 (C-3), 67.6 (CC-c-Pr), 9.0 (2CH2 c-Pr), 0.4 (CH c-Pr). m.p.: 79-83°C. HRMS (ESI): m/z calculated for C12H9BrN2 [M+H]+ : 261.00219, found: 261.00244.

General procedure for Sonogashira coupling at C-3 position.4a-b (0.5mmol, 1eq), PdCl2(PPh3)2 (35mg, 0.05mmol, 10%) and CuI (10mg, 0.05mmol, 10%) were

introduced into a screw-cap test tube. The tube was sealed with a rubber septum and then evacuated and refilled with argon thrice. DMF (2mL), Et3N (278µL, 2mmol, 4eq) and alkyne (0.55mmol, 1.1eq) were then added. The reaction mixture was stirred for 1h30 at 80°C. After cooling, the reaction mixture was partitioned between CH2Cl2 (10mL) and brine (10mL). The aqueous phase was extracted twice with CH2Cl2 (10mL). Organic phases were combined, dried over MgSO4 and evaporated to dryness. The crude mixture was purified by column chromatography (silica, eluent: mixture of petroleum ether and diethylether).

2-(phenylethynyl)-3-(p-tolylethynyl)imidazo[1,2-a]pyridine (5a) Eluent: PE/Et2O 50/50. Orange solid, yield: 97%. 1H NMR (CDCl3) δ: 8.29 (d, 1H, J = 6.6Hz, H-5),

7.65-7.62 (m, 3H, Ph-2,6, H-8), 7.51 (d, 2H, J = 8.1Hz, tolyl-2,6), 7.39-7.35 (m, 3H, Ph-3,4,5), 7.32 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 7.21 (d, 2H, J = 7.8Hz, tolyl-3,5), 6.97 (td, 1H, J = 6.6Hz, 0.9Hz, H-6), 2.40 (s, 3H, CH3 tolyl). 13C NMR (CDCl3) δ: 144.7 (C-8a), 139.5 (tolyl-4), 132.0 (Ph-2,6), 131.9 (C-2), 131.5 (tolyl-2,6), 129.4 (tolyl-3,5), 128.9 (Ph-4), 128.5 (Ph-3,5), 127.1 (C-7), 125.3 (C-5), 122.7 (Ph-1), 119.3 (tolyl-1), 117.6 (C-8), 113.8 (C-6), 112.2 (C-3), 102.3 (CC-tolyl), 94.7 (CC-Ph), 82.3 (CC-Ph), 75.2 (CC-tolyl), 21.7 (CH3 tolyl). m.p.: 113-117°C. HRMS (ESI): m/z calculated for C24H17N2 [M+H]+ : 333.13917, found: 333.13888.

3-(cyclopropylethynyl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5b)Eluent: PE/Et2O 50/5040/60. Brown solid, yield: 82%. 1H NMR (CDCl3) δ: 8.16 (dt, 1H, J =

6.9Hz, 0.9Hz, H-5), 7.63-7.59 (m, 2H, Ph-2,6), 7.54 (dt, 1H, J = 9.0Hz, 0.9Hz, H-8), 7.38-7.33 (m, 3H, Ph-3,4,5), 7.24 (ddd, 1H, J = 9.0Hz, 6.6Hz, 1.2Hz, H-7), 6.88 (td, 1H, J = 6.6Hz, 0.9Hz, H-6), 1.70-1.61 (m, 1H, CH c-Pr), 1.04-0.91 (m, 4H, 2CH2 c-Pr). 13C NMR (CDCl3) δ: 144.5 (C-8a), 132.0 (Ph-2,6), 131.9 (C-2), 128.7 (Ph-4), 128.4 (Ph-3,5), 126.3 (C-7), 125.1 (C-5), 123.0 (Ph-1), 117.6 (C-8), 113.3 (C-6), 112.5 (C-3), 106.8 (CC-c-Pr), 93.7 (CC-Ph), 82.8 (CC-Ph), 62.4 (CC-c-Pr), 9.6 (2CH2 c-Pr), 0.8 (CH c-Pr). m.p.: 105-109°C. HRMS (ESI): m/z calculated for C20H14N2 [M+H]+ : 283.12298, found: 283.12315.

3-(3-methoxyprop-1-yn-1-yl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5c)Eluent: PE/Et2O 40/60. Brown oil, yield: 42%. 1H NMR (CDCl3) δ: 8.22 (dt, 1H, J = 6.9Hz, 0.9Hz,

H-5), 7.62-7.57 (m, 3H, Ph-2,6, H-8), 7.38-7.34 (m, 3H, Ph-3,4,5), 7.30 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 6.94 (td, 1H, J = 6.9Hz, 0.9Hz, H-6), 4.53 (s, 2H, CH2OCH3), 3.52 (s, 3H, CH2OCH3). 13C NMR (CDCl3) δ: 145.1 (C-8a), 133.2 (C-2), 132.0 (Ph-2,6), 128.9 (Ph-4), 128.5 (Ph-3,5), 126.9 (C-7), 125.2 (C-5), 122.7 (Ph-1), 117.8 (C-8), 113.7 (C-6), 111.2 (C-3), 98.2 (CC-CH2OCH3), 94.1 (CC-Ph), 82.3 (CC-Ph), 73.5 (CC-CH2OCH3), 60.8 (CH2OCH3), 57.9 (CH2OCH3). HRMS (ESI): m/z calculated for C19H14N2O [M+H]+ : 287.11789, found: 287.11822.

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2-(cyclopropylethynyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine (5d)Eluent: PE/Et2O 50/50. Brown oil, yield: 54%. 1H NMR (CDCl3) δ: 8.23 (dt, 1H, J = 6.9Hz, 0.9Hz,

H-5), 7.60-7.54 (m, 3H, Ph-2,6, H-8), 7.41-7.37 (m, 3H, Ph-3,4,5), 7.27 (ddd, 1H, J = 8.7Hz, 6.6Hz, 1.2Hz, H-7), 6.93 (td, 1H, J = 6.9Hz, 1.2Hz, H-6), 1.60-1.51 (m, 1H, CH c-Pr), 0.93-0.90 (m, 4H, 2CH2 c-Pr). 13C NMR (CDCl3) δ: 144.6 (C-8a), 132.9 (C-2), 131.5 (Ph-2,6), 128.9 (Ph-4), 128.6 (Ph-3,5), 126.8 (C-7), 125.1 (C-5), 122.5 (Ph-1), 117.5 (C-8), 113.6 (C-6), 113.3 (C-3), 101.5 (CC-Ph), 99.5 (CC-c-Pr), 76.1 (CC-Ph), 68.5 (CC-c-Pr), 9.1 (2CH2 c-Pr), 0.6 (CH c-Pr). HRMS (ESI): m/z calculated for C20H14N2 [M+H]+ : 283.12298, found: 283.12319.

3-((4-methoxyphenyl)ethynyl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5e)1b (200mg, 0.619mmol, 1eq), PdCl2(PPh3)2 (43mg, 0.062mmol, 10%) and CuI (12mg, 0.062mmol,

10%) were introduced into a screw-cap test tube. The tube was sealed with a rubber septum and then evacuated and refilled with argon thrice. DMF (2.5mL), Et3N (344µL, 2.48mmol, 4eq) and phenylacetylene (75µL, 0.68mmol, 1.1eq) were then added. The reaction mixture was stirred for 30 minutes at room temperature. 4-methoxyphenylacetylene (120µL, 0.929mmol, 1.5eq) was added, and the reaction heated at 80°C for 1h30. After cooling, the reaction mixture was partitioned between CH2Cl2 (12mL) and brine (12mL). The aqueous phase was extracted twice with CH2Cl2 (12mL). Organic phases were combined, dried over MgSO4 and evaporate to dryness. The crude mixture was purified by column chromatography (silica, eluent: PE/Et2O 40/6020/80) to afford 5e as a dark yellow solid (140mg), yield: 65%. 1H NMR (CDCl3) δ: 8.25 (dt, 1H, J = 6.6Hz, 0.9Hz, H-5), 7.65-7.59 (m, 3H, Ph-2,6, H-8), 7.54 (d, 2H, J = 8.7Hz, 4-MeOPh-2,6), 7.37-7.34 (m, 3H, Ph-3,4,5), 7.29 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.5Hz, H-7), 6.96-6.89 (m, 3H, 4-MeOPh-3,5, H-6), 3.83 (s, 3H, OCH3). 13C NMR (CDCl3) δ: 160.3 (4-MeOPh-4), 144.7 (C-8a), 133.4 (C-2*), 133.2 (4-MeOPh-2,6), 132.0 (Ph-2,6), 131.7 (4-MeOPh-1*), 128.8 (Ph-4), 128.4 (Ph-3,5), 126.9 (C-7), 125.2 (C-5), 122.7 (Ph-1), 117.6 (C-8), 114.3 (4-MeOPh-3,5), 113.7 (C-6), 112.3 (C-3), 102.1 (CC-4-MeOPh), 94.5 (CC-Ph), 82.4 (CC-Ph*), 74.5 (CC-4-MeOPh*), 55.4 (OCH3). m.p.: 54-58°C. HRMS (ESI): m/z calculated for C24H16N2O [M+H]+ : 349.13354, found: 349.13389.

2-methyl-3-(phenylethynyl)imidazo[1,2-a]pyridine (6b)Eluent: PE/Et2O 50/5020/80. Orange oil, yield: 67%. 1H NMR (CDCl3) δ: 8.24 (dt, 1H, J = 6.9Hz,

0.9Hz, H-5), 7.57-7.53 (m, 3H, Ph-2,6, H-8), 7.40-7.33 (m, 3H, Ph-3,4,5), 7.21 (ddd, 1H, J = 9.0Hz, 6.9Hz, 1.2Hz, H-7), 6.87 (td, 1H, J = 6.9Hz, 1.2Hz, H-6), 2.58 (s, 3H, CH3). 13C NMR (CDCl3) δ: 148.5 (C-2), 144.9 (C-8a), 131.3 (Ph-2,6), 128.6 (Ph-3,4,5), 125.7 (C-7), 125.1 (C-5), 122.9 (Ph-1), 116.9 (C-8), 112.8 (C-6), 106.4 (C-3), 100.7 (CC-Ph), 76.9 (CC-Ph), 14.4 (CH3). HRMS (ESI): m/z calculated for C16H12N2 [M+H]+ : 233.10732, found: 233.10744.

3-methyl-2-(phenylethynyl)imidazo[1,2-a]pyridine (6c)Eluent: CH2Cl2/MeOH 99/1. Brown solid, yield: 70%. 1H NMR (CDCl3) δ: 7.82 (dt, 1H, J = 6.9Hz,

0.9Hz, H-5), 7.60-7.53 (m, 3H, Ph-2,6, H-8), 7.37-7.33 (m, 3H, Ph-3,4,5), 7.18 (ddd, 1H, J = 9.3Hz, 6.9Hz, 1.2Hz, H-7), 6.85 (td, 1H, J = 6.6Hz, 0.9Hz, H-6), 2.59 (s, 3H, CH3). 13C NMR (CDCl3) δ: 144.5 (C-8a), 131.7 (Ph-2,6), 128.4 (Ph-3,4,5), 126.5 (C-2), 124.4 (C-7), 123.8 (C-3*), 123.2 (Ph-1*), 122.9 (C-5), 117.7 (C-8), 112.8 (C-6), 92.7 (CC-Ph), 83.1 (CC-Ph), 9.2 (CH3). m.p.: 119-123°C. HRMS (ESI): m/z calculated for C16H12N2 [M+H]+ : 233.10732, found: 233.10750.

2-(phenylethynyl)-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (6d)Eluent: CH2Cl2/MeOH 99/1. Off-white solid, yield: 89%. 1H NMR (CDCl3) δ: 8.81 (bd, 1H, J =

4.5Hz, Pyridyl-2,6), 8.37 (d, 1H, J = 7.2Hz, H-5), 7.76 (d, 1H, J = 5.7Hz, Pyridyl-3,5), 7.67 (d, 1H, J = 9.0Hz, H-8), 7.54-7.48 (m, 2H, Ph-2,6), 7.37-7.30 (m, 4H, Ph-3,4,5, H-7), 6.93 (td, 1H, J = 6.9Hz, 0.9Hz, H-6). 13C NMR (CDCl3) δ: 150.1 (Pyridyl-2,6), 146.2 (C-8a), 136.9 (Pyridyl-4), 131.9 (Ph-2,6), 129.0 (Ph-4), 128.9 (C-2), 128.6 (Ph-3,5), 126.8 (C-7), 124.6 (Ph-1), 123.4 (C-5), 122.4 (Pyridyl-3,5), 118.5 (C-8), 114.2 (C-6), 93.4 (CC-Ph), 82.7 (CC-Ph), (C-3 is missing). m.p.: 87-91°C. HRMS (ESI): m/z calculated for C20H13N3 [M+H]+ : 296.11822, found: 296.11851.

6

2,3-diiodoimidazo[1,2-a]pyridine (1a) 1H NMR (CDCl3)

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

f1 (ppm)

-2E+08

0 2E+08

4E+08

6E+08

8E+08

1E+09

1E+09

1E+09

2E+09

2E+09

2E+09

2E+09

2E+09

3E+09

3E+09

3E+09

1.06

1.08

1.05

1.00

6.876.876.896.896.926.927.207.217.26 Chloroform-d

7.537.56

8.058.08

N

N

I

I

2,3-diiodoimidazo[1,2-a]pyridine (1a) 13C NMR (CDCl3)

7

010

2030

4050

6070

8090

100110

120130

140150

160f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

73.01

77.16 Chloroform-d

104.60

113.90

117.16

125.71126.96

149.44

N

N

I

I

3-bromo-2-iodoimidazo[1,2-a]pyridine (1b) 1H NMR (CDCl3)

8

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1E+09

1E+09

2E+09

2E+09

1.16

1.14

1.00

1.00

6.896.896.916.916.936.947.227.26 Chloroform-d

7.547.557.58

8.048.058.058.078.078.07

N

N

I

Br

3-bromo-2-iodoimidazo[1,2-a]pyridine (1b) 13C NMR (CDCl3)

9

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

77.16 Chloroform-d

95.87

101.88

113.75

117.28

124.29125.31

147.38

N

N

I

Br

2-iodo-3-phenylimidazo[1,2-a]pyridine (2a) 1H NMR (CDCl3)

10

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.5f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

1.00

1.03

4.851.04

1.02

6.736.736.756.766.786.787.197.197.217.26 Chloroform-d7.507.547.567.607.63

8.058.08

N

N

I

2-iodo-3-phenylimidazo[1,2-a]pyridine (2a) 13C NMR (CDCl3)

11

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-3E+08

-2E+08

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

77.16 Chloroform-d

93.66

112.98

117.26

123.30125.13128.39129.35130.19

146.96

N

N

I

3-bromo-2-phenylimidazo[1,2-a]pyridine (2b) 1H NMR (CDCl3)

12

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1E+09

1E+09

2E+09

2E+09

2E+09

1.00

1.230.941.961.03

2.88

6.906.906.926.926.946.957.26 Chloroform-d7.397.467.497.637.66

8.118.128.148.158.158.17

N

NBr

6.86.9

7.07.1

7.27.3

7.47.5

7.67.7

7.87.9

8.08.1

8.28.3

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

5E+08

1.00

1.23

0.94

1.96

1.03

2.88

6.906.906.926.926.946.95

7.237.237.257.26 Chloroform-d7.287.287.367.397.417.427.467.497.51

7.637.66

8.118.128.148.158.158.17

3-bromo-2-phenylimidazo[1,2-a]pyridine (2b) 13C NMR (CDCl3)

13

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

77.16 Chloroform-d

91.68

113.00

117.47

123.86125.08127.83128.27128.44

132.80

142.49

145.32

N

NBr

3-bromo-2-(thiophen-3-yl)imidazo[1,2-a]pyridine (2c) 1H NMR (CDCl3)

14

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.5f1 (ppm

)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1.06

1.330.951.00

0.86

1.69

6.906.936.957.26 Chloroform-d7.267.407.417.427.437.627.887.887.897.908.078.088.128.15

N

NBr

S

6.76.8

6.97.0

7.17.2

7.37.4

7.57.6

7.77.8

7.98.0

8.18.2

8.3f1 (ppm

)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

6.906.936.95

7.237.247.26 Chloroform-d7.267.297.297.407.417.427.43

7.627.66

7.887.887.897.90

8.078.088.128.15

3-bromo-2-(thiophen-3-yl)imidazo[1,2-a]pyridine (2c) 13C NMR (CDCl3)

15

-100

1020

3040

5060

7080

90100

110120

130140

150f1 (ppm

)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

77.16 Chloroform-d

91.50

113.36

117.38

123.78123.99125.56125.81127.05

133.89

139.09

145.16

N

NBr

S

3-bromo-2-methylimidazo[1,2-a]pyridine (2d) 1H NMR (CDCl3)

16

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.0f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

3.29

1.00

1.01

0.91

0.92

2.43

6.816.826.836.846.866.867.157.167.167.187.26 Chloroform-d7.467.49

7.988.00

N

N

CH3

Br

6.76.9

7.17.3

7.57.7

7.98.1

f1 (ppm)

0 1E+07

2E+07

3E+07

4E+07

5E+07

6E+07

7E+07

8E+07

9E+07

6.816.826.836.846.866.86

7.137.137.157.157.167.167.187.187.26 Chloroform-d

7.467.49

7.988.00

3-bromo-2-methylimidazo[1,2-a]pyridine (2d) 13C NMR (CDCl3)

17

1020

3040

5060

7080

90100

110120

130140

150f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

8E+08

13.68

77.16 Chloroform-d

93.00

112.63

117.02

123.67124.38

141.99

145.22

N

N

CH3

Br

2-phenyl-3-(p-tolyl)imidazo[1,2-a]pyridine (3a) 1H NMR (CDCl3)

18

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.0f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

1.00

1.106.98

2.77

0.99

2.46

6.686.696.716.716.736.737.26 Chloroform-d7.277.297.33

7.677.697.697.707.717.727.937.95

N

N

CH3

6.66.8

7.07.2

7.47.6

7.88.0

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

6.686.696.716.716.736.737.157.167.177.187.187.197.217.217.247.26 Chloroform-d7.277.297.33

7.677.697.697.707.717.72

7.937.95

2-phenyl-3-(p-tolyl)imidazo[1,2-a]pyridine (3a) 13C NMR (CDCl3)

19

1520

2530

3540

4550

5560

6570

7580

8590

95100

105110

115120

125130

135140

145150

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

21.52

77.16 Chloroform-d

112.26

117.49123.40124.68126.78127.48128.10128.31130.35130.63

134.28

138.93142.16144.74

N

N

CH3

3-(4-methoxyphenyl)-2-phenylimidazo[1,2-a]pyridine (3b) 1H NMR (CDCl3)

20

-1.0-0.5

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.09.5

10.0f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

3.09

1.00

1.971.143.001.95

2.85

0.95

3.89

6.696.706.726.726.746.747.047.077.187.187.197.217.247.26 Chloroform-d7.277.297.357.387.667.697.697.717.727.907.907.907.927.92

N

N

O

CH3

6.66.8

7.07.2

7.47.6

7.88.0

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

6.696.706.726.726.746.747.047.077.187.187.187.197.217.217.247.26 Chloroform-d7.277.297.357.38

7.667.697.697.717.727.907.907.907.927.927.93

3-(4-methoxyphenyl)-2-phenylimidazo[1,2-a]pyridine (3b) 13C NMR (CDCl3)

21

010

2030

4050

6070

8090

100110

120130

140150

160f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

55.46

77.16 Chloroform-d

112.23115.13117.57120.98121.93123.41124.58127.46128.04128.35132.19134.43

142.24144.74

160.09

N

N

O

CH3

3-(furan-2-yl)-2-phenylimidazo[1,2-a]pyridine (3c) 1H NMR (CDCl3)

22

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.5f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

1.81

1.08

1.073.19

0.821.102.01

1.00

6.566.576.776.786.806.806.826.827.357.377.637.657.747.747.767.77

8.188.188.188.208.208.21

N

N

O

6.56.7

6.97.1

7.37.5

7.77.9

8.18.3

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6.566.57

6.776.786.806.806.826.827.227.227.237.237.257.257.26 Chloroform-d7.317.337.357.377.39

7.627.637.637.657.687.687.747.747.767.77

8.188.188.188.208.208.21

3-(furan-2-yl)-2-phenylimidazo[1,2-a]pyridine (3c) 13C NMR (CDCl3)

23

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

77.16 Chloroform-d

111.59111.84112.79

117.63

124.76125.49128.15128.24128.46

134.03

143.44143.60145.26145.48

N

N

O

3-methyl-2-phenylimidazo[1,2-a]pyridine (3d) 1H NMR (CDCl3)

24

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.5f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

3.19

1.00

1.050.972.061.122.091.05

2.64

6.826.826.846.846.866.867.177.187.26 Chloroform-d7.357.377.447.477.497.637.667.797.817.827.887.90

N

N

CH3

6.76.8

6.97.0

7.17.2

7.37.4

7.57.6

7.77.8

7.98.0

f1 (ppm)

0 2E+07

4E+07

6E+07

8E+07

1E+08

1E+08

1E+08

6.826.826.846.846.866.86

7.147.157.177.177.177.187.207.207.26 Chloroform-d7.327.337.337.357.377.387.447.477.497.637.66

7.797.817.827.887.90

3-methyl-2-phenylimidazo[1,2-a]pyridine (3d) 13C NMR (CDCl3)

25

1020

3040

5060

7080

90100

110120

130140

150f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

9.76

77.16 Chloroform-d

112.15

116.02117.58

122.96123.62127.48128.49128.63

134.98

142.57144.48

N

N

CH3

3-phenyl-2-(thiophen-3-yl)imidazo[1,2-a]pyridine (3e) 1H NMR (CDCl3)

26

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

f1 (ppm)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

1.00

3.37

4.770.990.930.97

6.776.776.796.796.816.827.237.26 Chloroform-d7.277.487.487.517.567.637.637.757.907.92

N

NS

6.66.7

6.86.9

7.07.1

7.27.3

7.47.5

7.67.7

7.87.9

8.0f1 (ppm

)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

6.776.776.796.796.816.82

7.217.237.26 Chloroform-d7.277.297.30

7.487.487.517.567.627.637.637.63

7.757.787.897.907.907.927.927.92

3-phenyl-2-(thiophen-3-yl)imidazo[1,2-a]pyridine (3e) 13C NMR (CDCl3)

27

-100

1020

3040

5060

7080

90100

110120

130140

150f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

77.16 Chloroform-d

113.18116.89120.64123.59125.64126.01127.02129.03129.67129.85131.10134.24137.46

143.95

N

NS

2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (3f) 1H NMR (CDCl3)

28

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.59.0

9.5f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

1.00

6.172.331.021.01

1.96

6.906.926.957.26 Chloroform-d7.337.347.357.437.447.607.617.627.638.128.15

8.79

N

N

N

7.07.5

8.08.5

9.0f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

6.906.926.957.26 Chloroform-d7.337.347.357.367.377.437.44

7.607.617.627.63

7.857.88

8.128.15

8.79

2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (3f) 13C NMR (CDCl3)

29

-100

1020

3040

5060

7080

90100

110120

130140

150160

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

77.16 Chloroform-d

114.07117.64118.32

123.23124.83126.99128.68128.85132.13

137.74

143.01144.97

150.95

N

N

N

3-bromo-2-(phenylethynyl)imidazo[1,2-a]pyridine (4a) 1H NMR (CDCl3)

30

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.59.0

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1.06

1.193.02

3.17

1.00

6.966.966.986.987.007.017.357.377.387.617.64

8.068.078.078.098.098.09

N

NBr

6.86.9

7.07.1

7.27.3

7.47.5

7.67.7

7.87.9

8.08.1

8.2f1 (ppm

)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

6.966.966.986.987.007.017.26 Chloroform-d7.287.307.317.317.317.337.347.357.377.387.38

7.617.627.637.64

8.068.078.078.098.098.09

3-bromo-2-(phenylethynyl)imidazo[1,2-a]pyridine (4a) 13C NMR (CDCl3)

31

-100

1020

3040

5060

7080

90100

110120

130140

150f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

8E+08

77.16 Chloroform-d

81.03

94.65

99.44

114.09

117.72

122.51124.10126.23128.50129.02132.01

145.17

N

NBr

3-bromo-2-(cyclopropylethynyl)imidazo[1,2-a]pyridine (4b) 1H NMR (CDCl3)

32

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

4.11

0.80

1.00

1.00

0.95

0.93

0.870.89

1.451.471.501.521.54

6.856.856.876.886.906.907.197.207.207.467.49

7.957.957.967.977.987.98

N

NBr

3-bromo-2-(cyclopropylethynyl)imidazo[1,2-a]pyridine (4b) 13C NMR (CDCl3)

33

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

0.40

8.97

67.57

77.16 Chloroform-d

98.3998.91

113.56

117.49

123.83125.49129.09

144.90

N

NBr

2-(phenylethynyl)-3-(p-tolylethynyl)imidazo[1,2-a]pyridine (5a) 1H NMR (CDCl3)

34

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

2.76

1.00

1.903.841.922.85

0.95

2.40

6.956.956.976.976.997.007.207.227.26 Chloroform-d7.307.307.327.337.337.357.367.377.387.507.537.627.637.647.668.288.30

N

N

CH3

6.97.1

7.37.5

7.77.9

8.18.3

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

6.956.956.976.976.997.007.207.227.26 Chloroform-d7.337.357.367.37

7.507.537.627.637.647.66

8.288.30

2-(phenylethynyl)-3-(p-tolylethynyl)imidazo[1,2-a]pyridine (5a) 13C NMR (CDCl3)

35

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

21.73

75.2577.16 Chloroform-d

82.28

94.72

102.34

112.24113.83117.65119.32122.73125.30127.10128.48128.91129.44131.51132.04

139.46

144.73

N

N

CH3

3-(cyclopropylethynyl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5b) 1H NMR (CDCl3)

36

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

4.06

0.81

1.00

1.392.961.081.95

0.91

0.910.950.980.991.021.031.041.611.631.651.651.681.70

6.866.866.886.896.906.917.26 Chloroform-d7.347.357.367.597.60

8.158.158.168.178.188.18

N

N

6.87.0

7.27.4

7.67.8

8.08.2

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6.886.896.906.917.237.247.247.247.26 Chloroform-d7.277.347.357.367.527.527.537.557.557.567.597.607.617.638.158.158.168.178.188.18

3-(cyclopropylethynyl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5b) 13C NMR (CDCl3)

37

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

8E+08

8E+08

0.84

9.62

62.39

77.16 Chloroform-d

82.76

93.66

106.84

112.52113.28

117.65

122.96125.09126.35128.42128.70131.93131.98

144.51

N

N

3-(3-methoxyprop-1-yn-1-yl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5c) 1H NMR (CDCl3)

38

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.59.0

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

2.82

1.97

1.00

1.202.872.92

0.93

3.52

4.53

6.916.926.946.946.966.967.26 Chloroform-d7.357.357.367.377.597.607.60

8.218.23

N

N

O

CH3

6.87.0

7.27.4

7.67.8

8.08.2

f1 (ppm)

0 5E+07

1E+08

2E+08

2E+08

6.916.926.946.946.966.967.26 Chloroform-d7.357.357.367.377.37

7.577.597.607.607.62

8.218.23

3-(3-methoxyprop-1-yn-1-yl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5c) 13C NMR (CDCl3)

39

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1E+09

1E+09

2E+09

57.87

60.76

73.54

77.16 Chloroform-d

82.31

94.14

98.18

111.16

113.71

117.82

122.69125.22126.90128.46128.91132.03133.20

145.06

N

N

O

CH3

2-(cyclopropylethynyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine (5d) 1H NMR (CDCl3)

40

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.5f1 (ppm

)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1E+09

1E+09

4.17

0.86

1.00

1.392.982.97

0.91

0.910.910.920.93

1.511.531.551.571.60

6.906.906.926.936.956.957.26 Chloroform-d7.377.387.397.397.547.577.587.59

8.228.248.24

N

N

6.87.0

7.27.4

7.67.8

8.08.2

f1 (ppm)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

6.906.906.926.936.956.957.26 Chloroform-d7.277.277.377.387.397.39

7.547.577.587.597.60

8.228.248.24

2-(cyclopropylethynyl)-3-(phenylethynyl)imidazo[1,2-a]pyridine (5d) 13C NMR (CDCl3)

41

-100

1020

3040

5060

7080

90100

110120

130140

150f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

0.60

9.12

68.54


99.54101.48

111.31113.60117.47

122.55125.14126.78128.60128.92131.53132.89

144.59

N

N

3-((4-methoxyphenyl)ethynyl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5e) 1H NMR (CDCl3)

42

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

3.28

3.35

4.112.393.02

1.00

6.896.906.926.926.946.946.966.967.347.357.367.537.567.62

8.248.248.258.268.27

N

N

O

CH3

6.66.8

7.07.2

7.47.6

7.88.0

8.28.4

f1 (ppm)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

6.896.906.926.926.946.946.967.26 Chloroform-d7.277.297.297.307.327.327.347.357.367.537.567.597.607.617.627.648.248.248.258.268.27

3-((4-methoxyphenyl)ethynyl)-2-(phenylethynyl)imidazo[1,2-a]pyridine (5e) 13C NMR (CDCl3)

43

010

2030

4050

6070

8090

100110

120130

140150

160f1 (ppm

)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

8E+08

55.45


82.41

94.49

102.06

112.33113.70114.29117.56122.72125.22126.93128.43128.83131.68131.96133.18133.45

144.66

160.30

N

N

O

CH3

2-phenyl-3-(phenylethynyl)imidazo[1,2-a]pyridine (6a) 1H NMR (CDCl3)

44

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1E+09

1E+09

1.10

1.344.292.252.001.00

2.78

6.936.936.956.966.986.987.26 Chloroform-d7.407.417.427.487.517.607.61

8.378.378.398.408.41

N

N

6.87.0

7.27.4

7.67.8

8.08.2

8.4f1 (ppm

)

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

6.936.936.956.966.986.987.26 Chloroform-d7.287.297.317.317.327.347.347.407.417.427.447.487.517.537.607.617.627.637.707.73

8.378.378.398.408.41

2-phenyl-3-(phenylethynyl)imidazo[1,2-a]pyridine (6a) 13C NMR (CDCl3)

45

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

77.16 Chloroform-d78.24

101.44

104.85

113.28

117.54122.78125.31126.65127.42128.72128.78128.90131.38133.33

145.19

147.81

N

N

2-methyl-3-(phenylethynyl)imidazo[1,2-a]pyridine (6b) 1H NMR (CDCl3)

46

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

2.91

1.00

1.022.932.92

0.84

2.58

6.856.856.876.876.896.907.357.357.377.547.547.567.56

8.228.238.238.258.258.25

N

N

CH3

6.87.0

7.27.4

7.67.8

8.08.2

f1 (ppm)

0 5E+07

1E+08

2E+08

2E+08

6.856.876.876.896.907.197.197.217.217.227.227.247.247.26 Chloroform-d7.357.357.377.397.537.547.547.567.567.578.228.238.238.258.258.25

2-methyl-3-(phenylethynyl)imidazo[1,2-a]pyridine (6b) 13C NMR (CDCl3)

47

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

1E+09

1E+09

1E+09

1E+09

2E+09

2E+09

2E+09

14.40


100.74

106.37

112.77

116.89

122.92125.06125.69128.57131.27

144.87

148.47

N

N

CH3

3-methyl-2-(phenylethynyl)imidazo[1,2-a]pyridine (6c) 1H NMR (CDCl3)

48

-0.50.0

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.5f1 (ppm

)

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

3.00

1.00

1.033.093.06

1.05

2.59

6.826.836.856.856.876.877.26 Chloroform-d7.337.347.357.367.537.537.567.577.587.597.607.807.83

6.87.0

7.27.4

7.67.8

8.0f1 (ppm

)

0 5E+07

1E+08

2E+08

6.826.836.856.856.876.877.187.197.197.217.26 Chloroform-d7.337.347.357.367.37

7.537.537.567.577.587.597.607.807.83

N

N

CH3

3-methyl-2-(phenylethynyl)imidazo[1,2-a]pyridine (6c) 13C NMR (CDCl3)

49

010

2030

4050

6070

8090

100110

120130

140150

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

9.18

77.16 Chloroform-d

83.07

92.73

112.76

117.74

122.95123.25123.78124.40126.46128.45131.74

144.48

N

N

CH3

2-(phenylethynyl)-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (6d) 1H NMR (CDCl3)

50

3.43.8

4.24.6

5.05.4

5.86.2

6.67.0

7.27.4

7.67.8

8.28.6

9.09.4

f1 (ppm)

-5E+07

0 5E+07

1E+08

2E+08

2E+08

2E+08

3E+08

4E+08

4E+08

4E+08

5E+08

6E+08

6E+08

6E+08

7E+08

8E+08

8E+08

8E+08

9E+08

1.00

3.78

1.921.001.93

0.96

1.92

6.916.916.936.936.956.967.26 Chloroform-d7.307.347.347.357.367.507.517.527.537.657.697.757.77

8.358.38

8.808.82

N

N

N

2-(phenylethynyl)-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (6d) 13C NMR (CDCl3)

51

-100

1020

3040

5060

7080

90100

110120

130140

150160

f1 (ppm)

-1E+08

0 1E+08

2E+08

3E+08

4E+08

5E+08

6E+08

7E+08

8E+08

9E+08

1E+09

77.16 Chloroform-d

82.72

93.39

114.18118.48122.40123.40124.60126.77128.57128.89129.05131.86

136.90

146.17

150.06

N

N

N

Documents

by Suzuki and Sonogashira cross-coupling reactions ... · 1 Regiocontrolled functionalization of 2,3-dihalogenoimidazo[1,2-a]pyridines by Suzuki and Sonogashira cross-coupling reactions