Methyl iodide → HCID 66673531, compound

HRID 423429Notes

Reaction equation

HRID 423429 reaction equation
C(O[C:6](=O)[NH:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([C:28]5[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=5)[S:27][C:21]=4[C:20]3=[O:35])=[CH:15][N:14]=2)[CH2:9]1)(C)(C)C.[H-].[Na+].IC>CN(C=O)C>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]2[S:27][C:21]3[C:20](=[O:35])[N:19]([C:16]4[CH:15]=[N:14][C:13]([N:10]5[CH2:11][CH2:12][C@@H:8]([NH:7][CH3:6])[CH2:9]5)=[CH:18][CH:17]=4)[CH2:24][CH2:23][C:22]=3[CH:25]=2)=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66674063HCID 66674063, compound

Product 1

HCID 66673531HCID 66673531, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dissolve ((R)-1-{5-[2-(4-chloro-phenyl)-7-oxo-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-pyridin-2-yl}-pyrrolidin-3-yl)-carbamic acid tert-butyl ester (0.367 g, 0.70 mmol) in DMF (10 mL). Treat the mixture with 60% NaH (33.7 mg, 0.84 mmol). Stir the resulting suspension at room temperature for 1 h. Add iodomethane (66 μL, 1.05 mmol) and stir at room temperature for 3 h. Quench the mixture with water (35 mL) and extract with EtOAc (3×40 mL). Wash the combined organic layers with water (3×30 mL), dry with Na2SO4, filter, and concentrate. Dissolve the resulting crude material in CH2Cl2 (5 mL), treat with TFA (3 mL) and stir at room temperature for 1 h. Remove the excess reagent in vacuo. Dilute the residue with CHCl3 (40 mL) and wash with 2.0 M NaOH (30 mL). Treat the cloudy organic layer with CH3OH (1.0 mL), dry with Na2SO4, filter, and concentrate. Purify the crude material by chromatography, eluting with 10% CH3OH (with 2M NH3)/CHCl3 to give 0.222 g (72%) of 2-(4-chloro-phenyl)-6-[6-((R)-3-methylamino-pyrrolidin-1-yl)-pyridin-3-yl]-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one.

Workup

  1. customQuench the mixture with water (35 mL)
  2. extractionextract with EtOAc (3×40 mL)
  3. washWash the combined organic layers with water (3×30 mL)
  4. dry with materialdry with Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. dissolutionDissolve the resulting crude material in CH2Cl2 (5 mL)
  8. additiontreat with TFA (3 mL)
  9. stirringstir at room temperature for 1 h
  10. customRemove the excess reagent in vacuo
  11. additionDilute the residue with CHCl3 (40 mL)
  12. washwash with 2.0 M NaOH (30 mL)
  13. additionTreat the cloudy organic layer with CH3OH (1.0 mL)
  14. dry with materialdry with Na2SO4
  15. filtrationfilter
  16. concentrationconcentrate
  17. customPurify the crude material by chromatography
  18. washeluting with 10% CH3OH (with 2M NH3)/CHCl3

Sources & evidence

ORD record
ord-d32c6bcf04674de0994affcc35ee47e0
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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