4-Ethynyl-1-methyl-1H-pyrazole → 2-bromo-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amine

HRID 2205864Notes

Reaction equation

HRID 2205864 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5](I)=[CH:4][N:3]=1.[C:10]([C:12]1[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=1)#[CH:11]>CN(C=O)C.C(N(CC)CC)C.C(OCC)(=O)C.[Cu]I.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>[Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([C:11]#[C:10][C:12]2[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=2)=[CH:4][N:3]=1

Participants

8

Reactant 2

HCID 511383214-Ethynyl-1-methyl-1H-pyrazoleHCID 601457042-Bromo-5-iodopyridin-4-amine

Product 1

HCID 867062772-bromo-5-((1-methyl-1H-pyrazol-4-yl)ethynyl)pyridin-4-amineYield 88.2%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-Amino-2-bromo-5-iodopyridine (5) (2.58 g 8.63 mmole), copper(I) iodide (164 mg 0.86 mmole) and bis(triphenylphosphine)palladium dichloride (216 mg 0.432 mmole) were weighed into a 100 mL flask and DMF (25 mL) with triethylamine (22 mL) was added. The mixture was stirred at r.t. for 15 minutes under nitrogen. 4-Ethynyl-1-methyl-1H-pyrazole (20) (945 mg at 100%, 8.91 mmole) in DMF (10 mL) and triethylamine (5 mL) was added to the flask. The reaction was stirred at r.t. for 1.75 hrs. The reaction was diluted with ethyl acetate (450 mL) and the solution was washed with water (3×240 mL), brine (120 mL), dried and evaporated. The residue was flash chromatographed (silica/ethyl acetate) to give the title compound (2.11 g, 88%). 1H-NMR (CDCl3, 500 MHz): δ 3.94 (s, 3H), 4.80 (br s, 2H), 6.79 (s, 1H), 7.59 (s, 1H), 7.66 (s, 1H), 8.15 (s, 1H).

Workup

  1. stirringThe reaction was stirred at r.t. for 1.75 hrs
  2. washthe solution was washed with water (3×240 mL), brine (120 mL)
  3. customdried
  4. customevaporated
  5. customchromatographed (silica/ethyl acetate)

Sources & evidence

ORD record
ord-0b67e1aed9f143caa376a7ef6b23a970
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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