Triethylamine → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,4-[(1e)-2-ethoxyethenyl]-1-[(4-fluorophenyl)methyl]-,ethyl ester

HRID 640703Notes

Reaction equation

HRID 640703 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:15](OS(C(F)(F)F)(=O)=O)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[CH2:31]([O:33][CH:34]=[CH:35][Sn](CCCC)(CCCC)CCCC)[CH3:32].C(N(CC)CC)C>CN(C=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>[CH2:34]([O:33]/[CH:31]=[CH:32]/[C:15]1[C:14]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:13][CH:12]=[C:11]2[N:7]([CH2:6][C:5]3[CH:29]=[CH:30][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=[CH:9][C:10]=12)[CH3:35]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 2763294(Z)-1-Ethoxy-2-(tributylstannyl)etheneHCID 768529391h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-4-[[(trifluoromethyl)sulfonyl]oxy]-,ethyl ester

Product 1

HCID 686655661h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,4-[(1e)-2-ethoxyethenyl]-1-[(4-fluorophenyl)methyl]-,ethyl ester

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a stirred solution of ethyl 1-(4-fluorobenzyl)-4-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (10.09, 22.4 mmol) and ethoxyvinyl tributyltin [prepared according to A. Leusik, H. A. Budding, J. W. Marsman, J. Organomet. Chem., 1967, 9, 285-294] (9.7 g, 26.9 mmol, mixture of E-1,2: Z-1,2:1:1, ratio=1:0.3:0.1) in DMF (30 mL) under a nitrogen atmosphere were added triethylamine (3.2 mL, 22.4 mmol) and dichlorobis(triphenylphosphine)palladium(II) (1.0 g, 1.4 mmol). The resulting mixture was heated to 140° C. for 10 minutes. It was quenched with aq NaHCO3 solution, and extracted with ethyl acetate. The organic layer was washed with brine (2×), dried over sodium sulfate, concentrated in vacuo and purified by Biotage flash chromatography. Elution with hexane:ethyl acetate (3:2) provided the title compound as a brown glue (2.1 g) pure E-isomer together with 5.6 g of a mixture of E-1,2 and Z-1,2 and 1,1 isomers). 1H NMR (DMSO-d6) δ; 8.69 (s, 1H), 7.85 (d, J=3.3 Hz, 1H), 7.33 (t, J=6.8 Hz, 2H), 7.13-7.20 (m, 3H), 6.86 (d, J=3.3 Hz, 1 H), 6.43 (d, J=13 Hz, 1H), 5.55 (s, 2H), 4.27 (q, J=7.2 Hz, 2 H), 3.98 (q, J=7.0 Hz, 2 H), 1.29 (t, J=7.1 Hz, 6 H). LCMS (APCl, M+H+): 369.1.

Workup

  1. customIt was quenched with aq NaHCO3 solution
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine (2×)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by Biotage flash chromatography
  7. washElution with hexane:ethyl acetate (3:2)

Sources & evidence

ORD record
ord-8d9e45b20f9b473992b5090bd10f3a27
Source dataset
uspto-grants-2010_04
Patent number
US07692014B2

Reaction notes

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