Lawesson's reagent → HCID 178461967, compound

HRID 243156Notes

Reaction equation

HRID 243156 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=O)[C@@H:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][N:17]3C2CCCCO2)[CH3:11])=[C:4]([NH:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)[CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:45])=CC=1>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[S:45])[C@@H:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][NH:17]3)[CH3:11])=[C:4]([NH:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)[CH:3]=1

Participants

5

Reactant 2

HCID 87949Lawesson's reagent2×HCID 68158153HCID 68158153, compound

Product 1

HCID 178461967HCID 178461967, compoundYield 12.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)—N-[4-Fluoro-2-(pyrimidin-4-ylamino)phenyl]-2-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-ylamino]propionamide (88 mg, 0.18 mmol) and Lawesson's reagent (298 mg, 0.74 mmol) were heated at reflux in THF (4 mL) under nitrogen for 16 h. Further Lawesson's reagent (150 mg, 0.37 mmol) was added and the reaction refluxed for a further 24 h. The reaction mixture was cooled, diluted with EtOAc (30 mL) and extracted with 1M HCl (2×5 mL). The aqueous extracts were basified with Na2CO3 and extracted with EtOAc (2×20 mL). The combined organic extracts were dried (Na2SO4), concentrated in vacuo and purified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM to give the title compound as a colourless gum, (9 mg, 12%). LCMS (Method B): RT 1.88 min [M+H]+ 410.09

Workup

  1. temperaturethe reaction refluxed for a further 24 h
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted with 1M HCl (2×5 mL)
  4. extractionextracted with EtOAc (2×20 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM

Sources & evidence

ORD record
ord-4207514821724a01bdcef0bedf0c2e11
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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