Hydrochloric Acid → 2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenylamine

HRID 472477Notes

Reaction equation

HRID 472477 reaction equation
[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

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 41539052-EthynylanilineHCID 674813708-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 674790482-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylethynyl)-phenylamine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

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 prepartory 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)+.

Workup

  1. extractionextracted with ethyl acetate (3×30 mL)
  2. washThe combined organic layers were washed with water (2×20 mL) and saturated aqueous sodium chloride (20 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified

Sources & evidence

ORD record
ord-826e9c8dd9894ed592d833044c1dbf5f
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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