Pyridine → HCID 57556446, compound

HRID 556369Notes

Reaction equation

HRID 556369 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[C:20](Cl)[N:19]=[C:18]([NH2:23])[N:17]=3)=[CH:11][C:8]=2[S:9][CH:10]=1)=[O:5])[CH3:2].N1C=CC=CC=1>C1COCC1.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH2:23])[N:17]=3)=[CH:11][C:8]=2[S:9][CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 1049PyridineHCID 86626628HCID 86626628, compound

Product 1

HCID 57556446HCID 57556446, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3.70 g (10.6 mMol) 6-(2-amino-6-chloro-pyrimidin-4-yloxy)-benzo[b]thiophene-3-carboxylic acid ethyl ester in 300 ml THF and 8.68 ml (108 mMol) pyridine is hydrogenated in presence of 3.0 g Pd/C (10%; added in 3 portions during 23 h). The mixture is filtered and the solid washed extensively with MeOH. The filter cake still contains product and is therefore stirred in EtOAc and water. The separated EtOAc layer is washed twice with water, added to the filtrate and concentrated. The residue is re-dissolved in 300 ml EtOAc and 50 ml MeOH. Then water is added, the aq. layer separated off and extracted 4× with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated together with 21 g SiO2. The resulting powder is put on top of a SiO2-column and the title compound eluated with EtOAc/hexane 9:1: m.p.: 144-145° C.; TLC(EtOAc/hexane 9:1): Rf=0.27.

Workup

  1. filtrationThe mixture is filtered
  2. washthe solid washed extensively with MeOH
  3. washThe separated EtOAc layer is washed twice with water
  4. additionadded to the filtrate
  5. concentrationconcentrated
  6. dissolutionThe residue is re-dissolved in 300 ml EtOAc
  7. additionThen water is added
  8. customthe aq. layer separated off
  9. extractionextracted 4× with EtOAc
  10. washThe organic layers are washed with water and brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated together with 21 g SiO2

Sources & evidence

ORD record
ord-d10a6c7e4a2b4ed184cc0b9b38621892
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

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