Triethylamine → 6-Bromo-2-(diethoxymethyl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridine

HRID 2205932Notes

Reaction equation

HRID 2205932 reaction equation
C(N(CC)CC)C.[CH2:8]([O:10][CH:11]([O:14][CH2:15][CH3:16])[C:12]#[CH:13])[CH3:9].[Br:17][C:18]1[CH:23]=[C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:21](I)=[CH:20][N:19]=1>[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.CN(C=O)C>[Br:17][C:18]1[N:19]=[CH:20][C:21]2[CH:13]=[C:12]([CH:11]([O:14][CH2:15][CH3:16])[O:10][CH2:8][CH3:9])[N:24]([S:25]([CH3:28])(=[O:27])=[O:26])[C:22]=2[CH:23]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 662853,3-DiethoxypropyneHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamide

Product 1

HCID 867063206-Bromo-2-(diethoxymethyl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridineYield 51%

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

To DMF (3.4 mL) containing triethylamine (0.64 mL, 0.46 g 4.5 mmole) was added propargylaldehyde diethyl acetal (183 uL, 163 mg, 1.27 mmole) and N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide, (Preparation 8, 400 mg 1.06 mmole) followed by copper(I) iodide (7.1 mg, 0.037 mmole). The reaction was placed under nitrogen. Bis(triphenylphosphine)palladium dichloride (26.1 mg, 0.037 mmole) was added and the reaction was flushed again with nitrogen, then heated at 60° C. for 2 hours. The reaction was cooled and added to water (35 mL) containing a sodium bicarbonate solution (3 mL). The reaction was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with water containing sodium bicarbonate solution (3×10 mL), brine and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 100% dichloromethane to 5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane to give the title compound (207 mg, 51%). 1H-NMR (CDCl3, 500 MHz): δ 1.32 (t, J=6.94 Hz, 6H), 3.38 (s, 3H), 3.75 (m, 2H), 3.84 (m, 2H), 5.86 (d, J=0.95 Hz, 1H), 6.94 (t, J=0.95 Hz, 1H), 8.14 (t, J=0.95 Hz, 1H), 8.67 (d, J=0.95 Hz, 1H).

Workup

  1. additionwas added
  2. customthe reaction was flushed again with nitrogen
  3. temperatureThe reaction was cooled
  4. additionadded to water (35 mL)
  5. additioncontaining a sodium bicarbonate solution (3 mL)
  6. extractionThe reaction was extracted with ethyl acetate (3×20 mL)
  7. washThe combined organic layers were washed with water
  8. additioncontaining sodium bicarbonate solution (3×10 mL), brine
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with 100% dichloromethane to 5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-086a562d38164ae5816bdbf229e082e6
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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