Triethylamine → 3-((4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)methyl)-5-methylisoxazole

HRID 2205872Notes

Reaction equation

HRID 2205872 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5](I)=[CH:4][N:3]=1.[C:14]([C:16]1[CH:17]=[N:18][N:19]([CH2:21][C:22]2[CH:26]=[C:25]([CH3:27])[O:24][N:23]=2)[CH:20]=1)#[CH:15].C(N(CC)CC)C>CN(C=O)C.O.ClCCl.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)I>[Br:1][C:2]1[N:3]=[CH:4][C:5]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]4[CH:26]=[C:25]([CH3:27])[O:24][N:23]=4)[CH:20]=3)[N:8]([S:9]([CH3:12])(=[O:11])=[O:10])[C:6]=2[CH:7]=1

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamideHCID 867062833-((4-Ethynyl-1H-pyrazol-1-yl)methyl)-5-methylisoxazole

Product 1

HCID 867062843-((4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)methyl)-5-methylisoxazoleYield 52.1%

Reagents, catalysts & solvents 5

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Bis(triphenylphosphine)palladium dichloride (46 mg, 0.066 mmol) was added to a solution of N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide (8) (0.5 g, 1.32 mmol), 3-((4-ethynyl-1H-pyrazol-1-yl)methyl)-5-methylisoxazole (32) (0.278 g, 1.48 mmol), triethylamine (0.7 g, 7 mmol) and copper iodide (13 mg, 0.065 mmol) in DMF (5 ml). The reaction mixture was heated for 1 h at 60° C. The reaction mixture was cooled to room temperature and diluted with water (20 ml) and dichloromethane (30 ml). The organic solution was dried and concentrated in vacuo. The crude product was purified by flash silica chromatography (10 to 20% ethyl acetate in hexane) to afford the product as a white powder (300 mg, 51.8%). 1H-NMR (500 MHz, CDCl3) 2.43 (s, 3H), 2.96 (s, 3H), 5.41 (s, 2H), 6.02 (s, 1H), 6.69 (s, 1H), 7.78 (s, 1H), 7.87 (s, 1H), 8.22 (s, 1H), 8.62 (s, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic solution was dried
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash silica chromatography (10 to 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-3420180069364b38956c6984453ba5c5
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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