Cesium carbonate → HCID 89739691, compound

HRID 2206560Notes

Reaction equation

HRID 2206560 reaction equation
F[C:2]1[C:7]([I:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:9][C:10]([S@@:13]([NH2:15])=[O:14])([CH3:12])[CH3:11].[Cl-].[O:17]1[CH2:22][CH2:21][CH:20]([C@H:23]([NH3+:25])[CH3:24])[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[CH3:9][C:10]([S@@:13]([NH2:15])=[O:14])([CH3:12])[CH3:11].[I:8][C:7]1[C:2]([NH:25][C@@H:23]([CH:20]2[CH2:21][CH2:22][O:17][CH2:18][CH2:19]2)[CH3:24])=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 70095012-Fluoro-3-iodopyridineHCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 897415721269756-03-7

Product 2

HCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 89739691HCID 89739691, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
125 °C

Procedure

To a re-sealable vial containing 2-fluoro-3-iodopyridine (2.14 g, 9.60 mmol), (S)- or (R)-1-(tetrahydro-2H-pyran-4-yl)ethanaminium chloride (1.2175 g, 7.35 mmol) and cesium carbonate (7.54 g, 23.14 mmol) was added DMAc (10 mL). The vial was subsequently scaled and placed in a 125° C. bath. After stirring at 125° C. for 48 h, the reaction mixture was cooled to room temperature and partitioned between EtOAc with water. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were washed with a minimal amount of water (2×), dried over Na2SO4, and concentrated to give a heterogeneous brown oil. The oil was diluted with EtOAc/Hexanes (1:3) and filtered. The solids were washed with EtOAc:Hexanes (1:3) and the filtrate was concentrated to give a brown oil. The resultant oil was purified on a Biotage system (40 g, gradient elution 2% EtOAc: 98% Hexanes to 10% EtOAc: 900 Hexanes, then isocratic 10% EtOAc: 90% Hexanes). The product (S)- or (R)-3-iodo-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)pyridin-2-amine (0.84 g, 2.53 mmol, 34.4% yield) was isolated as a clear colorless oil. LRMS (M+H+) m/z: calcd 333.0. found 333.

Workup

  1. customplaced in a 125° C.
  2. temperaturethe reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc with water
  4. extractionThe aqueous layer was extracted with EtOAc (3×)
  5. washThe combined organic layers were washed with a minimal amount of water (2×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give a heterogeneous brown oil
  9. filtrationfiltered
  10. washThe solids were washed with EtOAc:Hexanes (1:3)
  11. concentrationthe filtrate was concentrated
  12. customto give a brown oil
  13. customThe resultant oil was purified on a Biotage system (
  14. wash40 g, gradient elution 2% EtOAc

Sources & evidence

ORD record
ord-21bac79d2a9b47eabea50ced803e5a09
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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