Water → 5-Trimethylsilylethynyl-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine

HRID 1845883Notes

Reaction equation

HRID 1845883 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=2[Cl:19])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:20][Si:21]([C:24]#[CH:25])([CH3:23])[CH3:22].[CH2:26](N(CC)CC)C.O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:20][Si:21]([C:24]#[C:25][C:2]1[CH:3]=[C:4]([O:9][CH:10]([C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=2[Cl:19])[CH3:26])[C:5]([NH2:8])=[N:6][CH:7]=1)([CH3:23])[CH3:22]

Participants

9

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 211114855-Bromo-3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridin-2-ylamine

Product 1

HCID 1234568855-Trimethylsilylethynyl-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridineYield 62.9%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

5-bromo-3-(2,6-dichloro-3-fluoro-benzyloxy)-pyridine-2-amine (3.8 g, 10 mmol), trimethylsilylethyne (3.87 mL, 28 mmol), triethylamine (Et3N, 4.15 mL, 30 mmol), triphenylphosphine (PPh3, 52 mg, 0.2 mmol) and bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2, 140.3 mg, 0.2 mmol) was dissolved in N,N-dimethyl formamide (DMF, 10 mL), to which argon gas was bubbled for 10 min, then CuI (19 mg, 0.1 mmol) was added, the resultant reaction liquid was stirred under heating at 90° C. After 4.5 h, the reaction liquid was cooled to room temperature, water (10 mL) was added to quench the reaction. The resultant mixture was extracted with ethyl acetate (3×20 mL), the organic phases were combined, washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated, the resultant residue was purified via silica gel column chromatography (PE/EA=3:1) to yield 2.5 g of the target product as brown solid.

Workup

  1. customwas bubbled for 10 min
  2. customthe resultant reaction liquid
  3. customthe reaction liquid
  4. temperaturewas cooled to room temperature
  5. customto quench
  6. customthe reaction
  7. extractionThe resultant mixture was extracted with ethyl acetate (3×20 mL)
  8. washwashed with water and saturated brine successively
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customthe resultant residue was purified via silica gel column chromatography (PE/EA=3:1)

Sources & evidence

ORD record
ord-68ec179b49284b9f9b0ede08d7e23fc6
Source dataset
uspto-grants-2015_02
Patent number
US08952002B2

Reaction notes

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