Ammonium Chloride → (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanol

HRID 1854477Notes

Reaction equation

HRID 1854477 reaction equation
[Cl:1][C:2]1[C:3](I)=[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.[Li]CCCC.[CH2:27]([N:34]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C@H:35]1[CH2:39][CH2:38][CH:37]([CH:40]=[O:41])[CH2:36]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[C:3]([CH:40]([CH:37]2[CH2:38][CH2:39][C@H:35]([N:34]([CH2:42][C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:36]2)[OH:41])=[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

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 467363645-Chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 58009967(3S)-3-(dibenzylamino)cyclopentanecarbaldehydeHCID 178418339Butyllithium2×

Product 1

HCID 58010290(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanolYield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A round-bottomed flask was charged with 5-chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (3.5 g, 8.05 mmol, Adesis) in THF (161 mL) to give a colorless solution. The solution was cooled to about −78° C. and n-BuLi (1.6 M in hexanes, 6.54 mL, 10.46 mmol) was added drop-wise over about 15 min. After addition of the n-BuLi solution was complete, (3S)-3-(dibenzylamino)cyclopentanecarbaldehyde (2.48 g, 8.45 mmol) in THF (10 mL) was added drop-wise over about 5 min. The reaction mixture was stirred for about 4 h at about −78° C. Saturated aqueous NH4Cl (40 mL) was added slowly and the mixture was stirred for about 5 min. The organic solvent was removed under reduced pressure and EtOAc (100 mL) was added. The layers were separated and the organic layer was washed with brine (3×50 mL), dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give a yellow oil that was purified by silica gel chromatography eluting with a gradient of 5-10% EtOAc in heptane. The product containing fractions were combined and concentrated to give (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3S)-3-(dibenzylamino)cyclopentyl)methanol (3.5 g, 72%): LC/MS (Table 2, Method n) Rt=2.97 min; MS m/z: 603 (M+H)+.

Workup

  1. customto give a colorless solution
  2. stirringthe mixture was stirred for about 5 min
  3. customThe organic solvent was removed under reduced pressure and EtOAc (100 mL)
  4. additionwas added
  5. customThe layers were separated
  6. washthe organic layer was washed with brine (3×50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvent was removed under reduced pressure
  10. customto give a yellow oil that
  11. customwas purified by silica gel chromatography
  12. washeluting with a gradient of 5-10% EtOAc in heptane
  13. additionThe product containing fractions
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-d5ae4e907dfa4d9fadc5735ba5b3e849
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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