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

HRID 2205943Notes

Reaction equation

HRID 2205943 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][N:6]([CH2:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1)#[CH:2].[Br:13][C:14]1[CH:19]=[C:18]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:17](I)=[CH:16][N:15]=1.C(N(CC)CC)C>CN(C=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:13][C:14]1[N:15]=[CH:16][C:17]2[CH:2]=[C:1]([C:3]3[CH:4]=[N:5][N:6]([CH2:8][C:9]([F:11])([F:12])[F:10])[CH:7]=3)[N:20]([S:21]([CH3:24])(=[O:23])=[O:22])[C:18]=2[CH:19]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamideHCID 867063294-Ethynyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole

Product 1

HCID 867063306-Bromo-1-(methylsulfonyl)-2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridineYield 47.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
60 °C

Procedure

4-Ethynyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole (Preparation 148, 326 mg 1.87 mmole) was dissolved in DMF (4.9 mL) and N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide (Preparation 8, 565 mg 1.50 mmole) was added. To the solution was added triethylamine (0.91 mL, 655 mg 6.5 mmole) and copper(I) iodide (10 mg 0.052 mmole). The reaction was sealed and flushed with nitrogen. Bis(triphenylphosphine)palladium dichloride (37 mg 0.052 mmole) was added and the reaction was again flushed with nitrogen, then heated at 60° C. for 110 minutes. The reaction was cooled and added to water (50 ml). The reaction were extracted with ethyl acetate thrice (3×20 ml). The combined organic extracts were washed with water (3×20 mL) and brine, dried and concentrated in vacuo. The residue was purified using column chromatography eluting with 100% dichloromethane, 5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane to 30% ethyl acetate in dichloromethane to afford the title compound (300 mg, 47%). 1H-NMR (CDCl3, 500 MHz): δ 2.98 (s, 3H), 4.80 (q, J=8.20 Hz, 2H), 6.76 (d, J=0.95 Hz, 1H), 7.84 (d, J=0.63 Hz, 1H), 7.94 (s, 1H), 8.25 (t, J=0.95 Hz, 1H), 8.67 (d, J=0.95 Hz, 1H). 19F-NMR (CDCl3, 470.385 MHz): −71.56.

Workup

  1. customThe reaction was sealed
  2. customflushed with nitrogen
  3. customthe reaction was again flushed with nitrogen
  4. temperatureThe reaction was cooled
  5. additionadded to water (50 ml)
  6. extractionThe reaction were extracted with ethyl acetate thrice (3×20 ml)
  7. washThe combined organic extracts were washed with water (3×20 mL) and brine
  8. customdried
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with 100% dichloromethane, 5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane to 30% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-536eb89cbd904d60992a5477070efea2
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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