Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH2:9])#[CH:2].C(N(CC)C(C)C)(C)C.Br[C:20]1[C:21]2[N:22]([N:26]=[C:27]([Cl:29])[N:28]=2)[CH:23]=[CH:24][CH:25]=1.Cl>CN(C)C=O.[Cu]I>[Cl:29][C:27]1[N:28]=[C:21]2[C:20]([C:2]#[C:1][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[NH2:9])=[CH:25][CH:24]=[CH:23][N:22]2[N:26]=1
Reactant: C#Cc1ccccc1N
Reactant: Clc1nc2c(Br)cccn2n1
Agent: [Cu]I
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Nc1ccccc1C#Cc1cccn2nc(Cl)nc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
189 a) To a mixture of 2-ethynyl-phenylamine (126.0 mg, 1.075 mmol) and N,N-diisopropylethylamine (2 mL, 10 mmol) in N,N-dimethylformamide (1 mL) at room temperature under an atmosphere of nitrogen was added 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (250.0 mg, 1.075 mmol), bBis(triphenylphosphine)palladium(II) chloride (10.0 mg, 0.0142 mmol) and copper(I) iodide (7.0 mg, 0.037 mmol). The mixture was stirred at room temperature for 18 hours then was poured into 0.1N hydrochloric acid (100 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with water (2×20 mL) and saturated aqueous sodium chloride (20 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified using preparatory silica gel plates (20 cm×20 cm 100% dichloromethane). 2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenylamine was isolated as a yellow solid (0.158 g, 55%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.43 (d, J=6.7 Hz, 1H), 7.66 (d, J=7.4 Hz, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.19 (t, J=7.8 Hz, 1H), 7.07 (t, J=7.0 Hz, 1H), 6.77-6.67 (m, 2H), 4.81 (br s, 2H). MS=269, 271 (MH)+. 189 b) To a cooled solution of 2-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenylamine (840.0 mg, 3.126 mmol) and N,N-diisopropylethylamine (2.8 mL, 16 mmol) in 1,2-dichloroethane (10 mL) in a ice/water bath at 5° C. was added dropwise methanesulfonyl chloride (0.64 mL, 8.2 mmol). The mixture was stirred 1 hour at 5° C. then at room temperature overnight. 0.1N hydrochloric acid (50 mL) was added to reaction mixture, stirred for 20 minutes then extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water (50 mL) and saturated aqueous sodium chloride (50 mL), dried over magnesium sulfate, filtered and evaporated to a tan solid (1.34 g). To a suspension of the tan solid (1.34 g) from in tetrahydrofuran (10 mL,) was added 1.0 M of tetra-n-butylammonium fluoride in tetrahydrofuran (12.50 mL, 12.50 mmol). The mixture was stirred at room temperature for 18 hours. The volatiles were evaporated to yield a viscous oil. Hydrochloric acid (2N, 30 mL) was added to viscous oil and stirred then was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated. The residue was purified via chromatography (silica gel column 40 g 20%→100% ethyl acetate:hexane). N-[2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-methanesulfonamide was isolated as a tan solid (0.90 g, 83%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.50 (d, J=6.7 Hz, 1H), 7.93 (br s, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.71 (d, J=7.3 Hz, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.44 (t, J=7.9 Hz, 1H), 7.19 (t, J=7.8 Hz, 1H), 7.11 (t, J=7.1 Hz, 1H), 3.17 (s, 3H). MS=347, 349 (MH)+. 189 c) To a suspension of N-[2-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-methanesulfonamide (900.0 mg, 2.595 mmol) and cesium carbonate (950.0 mg, 2.916 mmol) in acetonitrile (5 mL) was added iodomethane (0.25 mL, 4.0 mmol). The reaction flask was capped and the mixture was stirred at room temperature over weekend. The volatiles were evaporated. The recovered solid was triturated with water (30 mL), filtered and rinsed with water then was dissolved in dichloromethane (50 mL) and was separated. The organic layer was dried over magnesium sulfate, filtered and evaporated. N-[2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-N-methyl-methanesulfonamide was isolated as a tan solid (0.871 g, 93%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.51 (d, J=6.7 Hz, 1H), 7.78 (d, J=7.4 Hz, 1H), 7.68 (d, J=7.6 Hz, 1H), 7.52 (d, J=7.8 Hz, 1H), 7.46 (t, J=7.4 Hz, 1H), 7.38 (t, J=7.5 Hz, 1H), 7.10 (t, J=7.1 Hz, 1H), 3.54 (s, 3H), 3.21 (s, 3H). MS=361, 363 (MH)+. 189 d) N-Methyl-N-(2-{2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl}-phenyl)-methanesulfonamide was prepared from N-[2-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenyl]-N-methyl-methanesulfonamide (125.0 mg, 0.3464 mmol) and 4-(4-methyl-piperazin-1-yl)-phenylamine (73.0 mg, 0.382 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (37.0 mg, 0.0677 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a yellow foam (0.138 g, 77%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.40 (d, J=6.6 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.61 (d, J=7.4 Hz, 1H), 7.55-7.48 (m, 3H), 7.43 (t, J=7.5 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.00 (d, J=7.7 Hz, 2H), 6.86 (t, J=7.0 Hz, 1H), 6.73 (s, 1H), 3.61 (s, 3H), 3.23-3.16 (m, 7H), 2.63-2.58 (m, 4H), 2.37 (s, 3H). MS=516 (MH)+.