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

HRID 1515703Notes

Reaction equation

HRID 1515703 reaction equation
[CH:1]1(/[CH:5]=[C:6](/[C:17]2[NH:26][C:20]3=[N:21][CH:22]=[C:23]([F:25])[CH:24]=[C:19]3[CH:18]=2)\[C:7]2[CH:12]=[CH:11][C:10]([S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH2:4][CH2:3][CH2:2]1>[Pd].CO>[CH:1]1([CH2:5][CH:6]([C:17]2[NH:26][C:20]3=[N:21][CH:22]=[C:23]([F:25])[CH:24]=[C:19]3[CH:18]=2)[C:7]2[CH:12]=[CH:11][C:10]([S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 532501452-[(E)-2-cyclobutyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 532512492-[2-cyclobutyl-1-(4-methanesulfonyl-phenyl)-ethyl]-5-fluoro-1H-pyrrolo[2,3-b]pyridineYield 17.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of [2-(E)-cyclobutyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-fluoro-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 46, 200 mg, 0.54 mmol) and 10% palladium on activated carbon (70 mg) in methanol (250 mL) was heated at 50° C. under hydrogen (50 psi) for 8 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. 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-cyclobutyl-1-(4-methanesulfonyl-phenyl)-ethyl]-5-fluoro-1H-pyrrolo[2,3-b]pyridine (35 mg, 17.5%) as a light yellow solid: LC/MS m/e calcd for C20H21FN2O2S [M+H]+ 373.46, observed 372.8; 1H NMR (400 MHz, CD3OD) δ ppm 8.03 (t, J=2.1 Hz, 1H), 7.88-7.93 (m, J=8.3 Hz, 2H), 7.67-7.79 (m, 1H), 7.56-7.61 (m, J=8.3 Hz, 2H), 6.42 (s, 1H), 4.20 (t, J=7.7 Hz, 1H), 3.06-3.19 (m, 3H), 2.16-2.40 (m, 3H), 1.93-2.08 (m, 2H), 1.64-1.90 (m, 4H).

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. customPurification

Sources & evidence

ORD record
ord-041a4818f0d14db7a718440cd1e0e95d
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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