HCID 66743453, compound → HCID 66743331, compound

HRID 1259352Notes

Reaction equation

HRID 1259352 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[N:16]=[C:15]3[C:17](=[CH2:31])[N:18]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH:25]=4)[C:19](=[O:20])[C:14]3=[CH:13][CH:12]=2)[CH:6]=[N:7][C:8]=1[O:9][CH3:10]>C1COCC1.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[N:16]=[C:15]3[CH:17]([CH3:31])[N:18]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH:25]=4)[C:19](=[O:20])[C:14]3=[CH:13][CH:12]=2)[CH:6]=[N:7][C:8]=1[O:9][CH3:10]

Participants

4

Reactant 1

HCID 66743453HCID 66743453, compound2×

Product 1

HCID 66743331HCID 66743331, compoundYield 68.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

As shown in step 22-v of Scheme 22, to a solution of 2-(5,6-dimethoxy-3-pyridyl)-7-methylene-6-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrrolo[3,4-b]pyridin-5-one (Compound 2071, 436 mg, 1.01 mmol) in THF (20 mL) was added Pd/C (200 mg, 10 wt % dry basis, wet, Degussa type). The reaction vessel was evacuated and then placed under an atmosphere of H2 (balloon). After stirring for 2.5 h, the reaction mixture was filtered through a pad of silica and washed with THF (80 mL). The resulting filtrate was concentrated under reduced pressure and the residue treated with EtOAc (6 mL). After heating to reflux to give a uniform suspension, hexanes (10 mL) were added. The resulting suspension was cooled to 0° C. (ice-water bath), held at 0° C. for 5 min, and the precipitate collected via filtration to give 2-(5,6-dimethoxy-3-pyridyl)-7-methyl-6-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-7H-pyrrolo[3,4-b]pyridin-5-one (Compound 254, 300 mg, 68%) as a pale tan-colored solid: ESMS (M+H) 434.44; 1H NMR (DMSO-d6, 300 MHz) δ 8.57 (d, J=3 Hz, 1H), 8.39 (s, 1H), 8.23 (d, J=9 Hz, 1H), 8.18 (d, J=9 Hz, 1H), 8.00 (d, J=3 Hz, 1H), 7.97 (s, 1H), 5.22 (m, 3H), 3.96 (s, 3H), 3.93 (s, 3H), 1.60 (d, J=6 Hz, 3H).

Workup

  1. customThe reaction vessel was evacuated
  2. filtrationthe reaction mixture was filtered through a pad of silica
  3. washwashed with THF (80 mL)
  4. concentrationThe resulting filtrate was concentrated under reduced pressure
  5. additionthe residue treated with EtOAc (6 mL)
  6. temperatureAfter heating
  7. temperatureto reflux
  8. customto give a uniform suspension, hexanes (10 mL)
  9. additionwere added
  10. waitheld at 0° C. for 5 min
  11. filtrationthe precipitate collected via filtration

Sources & evidence

ORD record
ord-83e6a08938a542d6851c82bfe0ee9f39
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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