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

HRID 2205912Notes

Reaction equation

HRID 2205912 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]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:20]=1)#[CH:15].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.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]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:20]=3)[N:8]([S:9]([CH3:12])(=[O:11])=[O:10])[C:6]=2[CH:7]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamideHCID 867063112-(4-Ethynyl-1H-pyrazol-1-yl)-N,N-dimethylacetamide

Product 1

HCID 867063122-(4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamideYield 88%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Bis(triphenylphosphine)palladiumdichloride (69 mg, 0.099 mmol) was added to a solution of N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide (Preparation 8, 0.5 g, 1.98 mmol), 2-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylacetamide (Preparation 101, 0.3 g, 1.7 mmol), triethylamine (1.05 g, 1.05 mmol) and copper iodide (19.5 mg, 0.098 mmol) in DMF (5 ml). The reaction mixture was heated for 1 hour at 60° C. The reaction was cooled to room temperature and diluted with ethyl acetate. The organic solution was washed with water, brine and dried over sodium sulphate. The solvent was removed in vacuum and the crude product purified on silica gel column chromatography eluting with a gradient of 10 to 20% methanol in ethyl acetate to afford the title compound as a white powder (0.3 g, 88%). 1H-NMR (500 MHz, d6-DMSO): δ 2.86 (s, 3H), 3.04 (s, 1H), 3.42 (s, 3H), 5.2 (s, 2H), 6.96 (s, 1H), 7.76 (s, 1H), 8.05 (s, 2H), 8.72 (s, 1H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washThe organic solution was washed with water, brine
  3. dry with materialdried over sodium sulphate
  4. customThe solvent was removed in vacuum
  5. customthe crude product purified on silica gel column chromatography
  6. washeluting with a gradient of 10 to 20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-8c593fc627784d9db2a793ed3b42157c
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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