Triethylamine → {(1R,3S)-3-[(6-Nitrothieno[3,2-b]pyridin-7-yl)amino]cyclopentyl}acetonitrile

HRID 712082Notes

Reaction equation

HRID 712082 reaction equation
CS(Cl)(=O)=O.[N+:6]([C:9]1[C:10]([NH:18][C@H:19]2[CH2:23][CH2:22][C@@H:21]([CH2:24]O)[CH2:20]2)=[C:11]2[S:17][CH:16]=[CH:15][C:12]2=[N:13][CH:14]=1)([O-:8])=[O:7].[CH2:26]([N:28](CC)CC)C.S([O-])(=O)(=O)C.[C-]#N.[Na+]>C(Cl)Cl.[Cl-].[Na+].O.CCOC(C)=O.CS(C)=O>[N+:6]([C:9]1[C:10]([NH:18][C@H:19]2[CH2:23][CH2:22][C@@H:21]([CH2:24][C:26]#[N:28])[CH2:20]2)=[C:11]2[S:17][CH:16]=[CH:15][C:12]2=[N:13][CH:14]=1)([O-:8])=[O:7]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 8929Sodium CyanideHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 86717537{(1R,3S)-3-[(6-Nitrothieno[3,2-b]pyridin-7-yl)amino]cyclopentyl}methanol

Product 1

HCID 86717538{(1R,3S)-3-[(6-Nitrothieno[3,2-b]pyridin-7-yl)amino]cyclopentyl}acetonitrileYield 13.2%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Methanesulfonyl chloride (24.0 μL, 0.310 mmol) was added to a solution of {(1R,3S)-3-[(6-nitrothieno[3,2-b]pyridin-7-yl)amino]cyclopentyl}methanol (70 mg, 0.2 mmol) and triethylamine (66.5 μL, 0.477 mmol) in methylene chloride (2.1 mL) at about 0° C. with stirring. The resulting mixture was allowed to warm to room temperature and stir overnight. The mixture was diluted with dichloromethane then washed with water and brine. The organic was dried (MgSO4), filtered, and concentrated to give a bright yellow gum. To the crude mesylate was added dimethyl sulfoxide (2.0 mL) and sodium cyanide (22 mg, 0.45 mmol). The resulting mixture was stirred at room temperature. After 2 h, the temperature was increased to 80° C. and stirred for 3 h. After cooling, EtOAc and brine were added. The layers were separated and the organic washed with water (2×), dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel, eluted with 10-70% EtOAc in hexanes to give 8 mg (10%) of the desired product. LCMS calculated for C14H15N4O2S (M+H)+: m/z=303.1. Found: 303.0.

Workup

  1. stirringstir overnight
  2. washthen washed with water and brine
  3. dry with materialThe organic was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a bright yellow gum
  7. stirringThe resulting mixture was stirred at room temperature
  8. temperaturethe temperature was increased to 80° C.
  9. stirringstirred for 3 h
  10. temperatureAfter cooling
  11. customThe layers were separated
  12. washthe organic washed with water (2×)
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe crude was purified on silica gel
  17. washeluted with 10-70% EtOAc in hexanes

Sources & evidence

ORD record
ord-74a4ff9fe7ea42ca9ab7f6b91b155242
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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