5-fluoro-2-[(E)-1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-1H-pyrrolo[2,3-b]pyridine → 5-fluoro-2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 1515898Notes

Reaction equation

HRID 1515898 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9](/[C:11](/[C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:12]/[CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[NH:8][C:5]2=[N:6][CH:7]=1>[Pd].CO>[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([CH:11]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH2:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 1

HCID 532303595-fluoro-2-[(E)-1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 532499855-fluoro-2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridineYield 60%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of 5-fluoro-2-[(E)-1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 122, 300 mg, 0.75 mmol) and 10% palladium on activated carbon (0.2 g) in methanol (50 mL) was heated at 45° C. under hydrogen (50 psi) for 5 h. After cooling to room temperature, the catalyst was removed by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo. The residue was 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 5-fluoro-2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridine as a white solid (180 mg, 60%): LC/MS m/e calcd for C21H23FN2O3S [M+H]+ 403.49, observed 403.2; 1H NMR (400 MHz, CD3OD) δ ppm 8.01 (t, J=2.1 Hz, 1H), 7.91 (d, J=8.3 Hz, 2H), 7.60-7.67 (m, 3H), 6.41 (s, 1H), 4.44 (t, J=8.1 Hz, 1H), 3.90 (d, J=11.4 Hz, 2H), 3.25-3.30 (m, 2H), 3.08-3.14 (m, 3H), 2.24 (dt, J=14.1, 7.3 Hz, 1H), 1.99-2.07 (m, 1H), 1.72 (t, J=14.1 Hz, 2H), 1.32-1.52 (m, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe catalyst was removed by filtration
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified

Sources & evidence

ORD record
ord-0a86c7ec4d4b4971ab0a21adf4ee963c
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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