2-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-2-methyl-propionic acid ethyl ester → 2-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-2-methyl-propionic acid ethyl ester

HRID 1515653Notes

Reaction equation

HRID 1515653 reaction equation
[CH2:1]([O:3][C:4](=[O:35])[C:5]([O:8][C:9]1[CH:10]=[C:11]2[CH:17]=[C:16]([C:18]([C:25]3[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=3)=[CH:19][CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[NH:15][C:12]2=[N:13][CH:14]=1)([CH3:7])[CH3:6])[CH3:2]>[Pd].CO>[CH2:1]([O:3][C:4](=[O:35])[C:5]([O:8][C:9]1[CH:10]=[C:11]2[CH:17]=[C:16]([CH:18]([C:25]3[CH:26]=[CH:27][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][CH:30]=3)[CH2:19][CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[NH:15][C:12]2=[N:13][CH:14]=1)([CH3:7])[CH3:6])[CH3:2]

Participants

4

Reactant 1

HCID 672283142-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-2-methyl-propionic acid ethyl ester

Product 1

HCID 583052662-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-2-methyl-propionic acid ethyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-2-methyl-propionic acid ethyl ester (1.04 g, 2.1 mmol) and 10% palladium on activated carbon (200 mg) in methanol (300 mL) was heated at 50° C. under hydrogen (50 psi) for 6 h. The mixture was cooled to room temperature. The catalyst was removed by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo and purified 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) to afford 2-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-2-methyl-propionic acid ethyl ester (700 mg, 70%) as a white solid: LC/MS m/e calcd for C27H34N2O5S [M+H]+ 499.65, observed 499.7; 1H NMR (400 MHz, CD3OD) δ ppm 1.24 (m, 2H), 1.30 (t, J=7.2 Hz, 3H), 1.51 (m, 2H), 1.57 (s, 6H), 1.60-1.90 (m, 5H, H), 2.13 (m, 1H), 2.29 (m, 1H), 3.10 (s, 3H), 4.26 (q, J=7.2 Hz, 2H), 4.33 (t, J=7.9 Hz, 1H), 6.46 (s, 1H), 7.61 (d, J=8.3 Hz, 2H), 7.71 (d, J=2.4 Hz, 1H), 7.91 (d, J=8.3 Hz, 2H), 7.92 (br, 1H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe catalyst was removed by filtration
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified

Sources & evidence

ORD record
ord-d1e228d42006455da9d3d249d4d5742e
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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