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

HRID 640697Notes

Reaction equation

HRID 640697 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:23]([O:25][CH3:26])=[O:24])[C:15](OC(=O)C(F)(F)F)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[CH2:29]([O:31]/[CH:32]=[CH:33]/[Sn](CCCC)(CCCC)CCCC)[CH3:30].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>[CH2:32]([O:31]/[CH:29]=[CH:30]/[C:15]1[C:14]([C:23]([O:25][CH3:26])=[O:24])=[N:13][CH:12]=[C:11]2[N:7]([CH2:6][C:5]3[CH:27]=[CH:28][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=[CH:9][C:10]=12)[CH3:33]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6508882Stannane, tributyl(2-ethoxyethenyl)-HCID 68665297methyl 1-(4-fluorobenzyl)-4-[(trifluoroacetyl)oxy]-1H-pyrrolo[2,3-c]pyridine-5-carboxylate

Product 1

HCID 686652681h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,4-[(1e)-2-ethoxyethenyl]-1-[(4-fluorophenyl)methyl]-,methyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a stirred solution of methyl 1-(4-fluorobenzyl)-4-[(trifluoroacetyl)oxy]-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (1.4 g, 3.24 mmol) and (E)-2-ethoxyvinyl tributyltin (E [prepared according to A. Leusik, H. A. Budding, J. W. Marsman, J. Organomet. Chem., 1967, 9, 285-294] (2.2 g, 6.48 mmol) in DMF (10 mL) under a nitrogen atmosphere were added triethylamine (0.48 mL, 3.24 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.24 g, 0.32 mmol). The resulting mixture was heated to 140° C. for 2 hours. It was quenched with water, and extracted with ethyl acetate three times. The combined organic extracts were washed with water (2×30 mL), dried over sodium sulfate, concentrated in vacuo and purified by Biotage flash chromatography. Elution with hexane:ethyl acetate (1:1) provided the title compound as brown glue (0.40 g, 35% yield). 1H NMR (MeOD) δ; 8.50 (s, 1H), 7.64 (d, 1H, J=3.3 Hz), 7.22 (t, 2H, J=6.8 Hz), 7.05 (t, 2H, J=6.8 Hz), 6.89 (d, 1H, J=3.3 Hz), 5.53 (s, 2H), 4.02 (q, 2H, J=7.1 Hz), 1.37 (t, 3H, J=7.1 Hz). LCMS (APCl, M+H+): 355.2.

Workup

  1. customIt was quenched with water
  2. extractionextracted with ethyl acetate three times
  3. washThe combined organic extracts were washed with water (2×30 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by Biotage flash chromatography
  7. washElution with hexane:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-d67dca5539df43e89a233da3ab222c1b
Source dataset
uspto-grants-2010_04
Patent number
US07692014B2

Reaction notes

Loading…