2-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-ethyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid → 2-{2-cyclopentyl-1-[3-fluoro-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-ethyl}-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid

HRID 1515723Notes

Reaction equation

HRID 1515723 reaction equation
[CH:1]1([CH2:6][CH:7]([C:25]2[NH:36][C:28]3=[N:29][CH:30]=[C:31]([C:33]([OH:35])=[O:34])[CH:32]=[C:27]3[CH:26]=2)[C:8]2[CH:13]=[CH:12][C:11]([C:14]([CH3:23])([O:16]C3CCCCO3)[CH3:15])=[C:10]([F:24])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)C>[CH:1]1([CH2:6][CH:7]([C:25]2[NH:36][C:28]3=[N:29][CH:30]=[C:31]([C:33]([OH:35])=[O:34])[CH:32]=[C:27]3[CH:26]=2)[C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])([CH3:23])[CH3:15])=[C:10]([F:24])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 1

HCID 672287672-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-ethyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid

Product 1

HCID 532514092-{2-cyclopentyl-1-[3-fluoro-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-ethyl}-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acidYield 28.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 2-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-ethyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (1.5 g, 3.04 mmol) in 95% ethanol (50 mL) was added cupric chloride dihydrate (52 mg, 0.3 mmol) at room temperature. The mixture was refluxed for 3 h and then cooled to room temperature. The resulting mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-{2-cyclopentyl-1-[3-fluoro-4-(1-hydroxy-1-methyl-ethyl)-phenyl]-ethyl}-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (350 mg, 28.1%) as a light yellow solid: LC/MS m/e calcd for C24H27FN2O3 [M+H]+ 411.49, observed 410.9; 1H NMR (400 MHz, CD3OD) δ ppm 8.79 (br. s., 1H), 8.56 (br. s., 1H), 7.53-7.60 (m, 1H), 7.13 (br. s., 1H), 7.02 (d, J=12.1 Hz, 1H), 6.51 (br. s., 1H), 4.19 (br. s., 1H), 2.22 (br. s., 1H), 2.12 (br. s., 1H), 1.61-1.88 (m, 5H), 1.56 (br. s., 6H), 1.51 (br. s., 2H), 1.23 (br. s., 2H).

Workup

  1. temperatureThe mixture was refluxed for 3 h
  2. concentrationThe resulting mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification

Sources & evidence

ORD record
ord-23a442319293408ca34cc7bff3d22dde
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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