Water → 2-Chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine

HRID 1890038Notes

Reaction equation

HRID 1890038 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[C:22]2[N:23]([N:27]=[C:28]([Cl:30])[N:29]=2)[CH:24]=[CH:25][CH:26]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O.O1CCOCC1>[Cl:30][C:28]1[N:29]=[C:22]2[C:21]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=3[O:32][CH3:31])=[CH:26][CH:25]=[CH:24][N:23]2[N:27]=1

Participants

10

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27339582-Methoxyphenylboronic acidHCID 674813708-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 674814532-Chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridineYield 83.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A Schlenck flask was charged with palladium acetate (0.0966 g, 0.430 mmol), triphenylphosphine (0.4513 g, 1.721 mmol), and 1,4-dioxane (6 mL) and the mixture was stirred for 5 min until it turned bright yellow. 8-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.500 g, 2.15 mmol), 2-methoxybenzeneboronic acid (0.490 g, 3.23 mmol), N,N-dimethylformamide (10.00 mL), and 1.00 N sodium carbonate in water (4.3 mL, 4.3 mmol) were added successively and the reaction was heated at 80° C. overnight, cooled to room temperature, diluted with dichloromethane, filtered through diatomaceous earth and concentrated. The reaction was purified via chromatography (silica gel 10%→20% ethyl acetate in hexanes) and concentrated to give 2-chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.464 g, 83%). MS=260 (MH)+. 311b) To an oven-dried Schlenck flask under an atmosphere of argon was added 2-chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.460 g, 1.77 mmol), 7-amino-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.558 g, 2.12 mmol), palladium acetate (0.0875 g, 0.390 mmol), 2,2-bis-dicyclohexylphosphanyl-biphenyl (0.242 g, 0.443 mmol), cesium carbonate (1.44 g, 4.43 mmol), followed by 1,4-dioxane (12.00 mL) and was degassed under an atmosphere of argon for 5 min and heated at 100° C. overnight, cooled at room temperature, diluted with dichloromethane, filtered through diatomaceous earth and concentrated. The reaction was purified via chromatography (silica gel 20%-30% ethyl acetate/hexanes) and concentrated to give 7-[8-(2-methoxy-phenyl)[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.744 g, 87%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.54 (s, 1H), 8.78 (d, 1H), 7.55 (m, 2H), 7.45 (m, 2H), 7.35 (s, 1H) 7.15 (m, 1H), 7.05 (m, 3H), 3.74 (s, 3H), 3.48 (m, 4H), 2.78 (m, 4H), 1.41 (s, 9H): MS=486 (MH)+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through diatomaceous earth
  3. concentrationconcentrated
  4. customThe reaction was purified via chromatography (silica gel 10%→20% ethyl acetate in hexanes)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5653d769469c40248d3b65ca3b641cb1
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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