Sodium Sulfite → (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanone

HRID 2204629Notes

Reaction equation

HRID 2204629 reaction equation
[Cl:1][C:2]1[C:3]([CH:21]([CH:23]2[CH2:27][CH2:26][C@H:25]([N:28]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:24]2)[OH:22])=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[C:5]2=[N:6][CH:7]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.S([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:3]([C:21]([CH:23]2[CH2:27][CH2:26][C@H:25]([N:28]([CH2:36][C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:24]2)=[O:22])=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:18]([CH3:19])[CH3:20])([CH:15]([CH3:16])[CH3:17])[CH:12]([CH3:14])[CH3:13])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24437Sodium SulfiteHCID 159087TriacetoxyperiodinaneHCID 58010290(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanol

Product 1

HCID 58009956(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanoneYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round-bottomed flask was charged with (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanol (3.51 g, 5.83 mmol) in DCM (104 mL) to give a yellow solution. The solution was cooled to about 0° C. Dess-Martin periodinane (7.41 g, 17.48 mmol) was added and the mixture was stirred at about 0° C. for about 2 h then at ambient temperature for about 3 h. The reaction mixture was then re-cooled to about 0° C. and saturated aqueous sodium sulfite (50 mL) was added slowly. The organic solvent was removed under reduced pressure. EtOAc (100 mL) was added and the layers were partitioned. The organic layer was washed with saturated aqueous NaHCO3 (2×20 mL) and brine (3×50 mL), dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to give a brown oil. The crude material was purified by silica gel chromatography eluting with 5% EtOAc in heptane. A second purification by neutral alumina chromatography eluting with a step-wise gradient of 0-100% EtOAc in heptane yielded (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanone (1.7 g, 50%) as a yellow oil: LC/MS (Table 2, Method n) Rt=3.90 min; MS m/z: 601 (M+H)+.

Workup

  1. customto give a yellow solution
  2. waitat ambient temperature for about 3 h
  3. temperatureThe reaction mixture was then re-cooled to about 0° C.
  4. customThe organic solvent was removed under reduced pressure
  5. additionEtOAc (100 mL) was added
  6. customthe layers were partitioned
  7. washThe organic layer was washed with saturated aqueous NaHCO3 (2×20 mL) and brine (3×50 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. customthe solvent was removed under reduced pressure
  11. customto give a brown oil
  12. customThe crude material was purified by silica gel chromatography
  13. washeluting with 5% EtOAc in heptane
  14. customA second purification by neutral alumina chromatography
  15. washeluting with a step-wise gradient of 0-100% EtOAc in heptane

Sources & evidence

ORD record
ord-7820fc8dd6c6481b92a449094b6603eb
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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