5-Chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine → (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3R)-3-(dibenzylamino)cyclopentyl)methanol

HRID 2204624Notes

Reaction equation

HRID 2204624 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>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

5

Reactant 3

HCID 467363645-Chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 58010065(3R)-3-(dibenzylamino)cyclopentanecarbaldehydeHCID 178418339Butyllithium

Product 1

HCID 58009958(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3R)-3-(dibenzylamino)cyclopentyl)methanolYield 67.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (1.23 g, 2.83 mmol, Adesis) in THF (10 mL) was cooled to about 78° C. and n-BuLi (1.6 M in hexanes, 2.3 mL, 3.7 mmol) was added drop-wise while keeping the temperature below about −70° C. The mixture was stirred for about 40 min, and a solution of (3R)-3-(dibenzylamino)cyclopentanecarbaldehyde (0.83 g, 2.8 mmol, Step B) in THF (3 mL) was added drop-wise, and the resulting mixture was stirred at about −75° C. for about 2 h. The reaction mixture was quenched by a drop-wise addition of saturated aqueous NH4Cl (20 mL), and the organic solvent was removed under reduced pressure. The aqueous mixture was extracted with EtOAc (25 mL) and the organic layer was washed with brine (20 mL) and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-20% EtOAc in heptane to yield (5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3R)-3-(dibenzylamino)cyclopentyl)methanol (1.14 g, 67%): LC/MS (Table 2, Method a) Rt=3.31 min; MS m/z: 602 (M+H)+.

Workup

  1. customthe temperature below about −70° C
  2. stirringthe resulting mixture was stirred at about −75° C. for about 2 h
  3. customThe reaction mixture was quenched by a drop-wise addition of saturated aqueous NH4Cl (20 mL)
  4. customthe organic solvent was removed under reduced pressure
  5. extractionThe aqueous mixture was extracted with EtOAc (25 mL)
  6. washthe organic layer was washed with brine (20 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of 0-20% EtOAc in heptane

Sources & evidence

ORD record
ord-e311e0c2375c4dd9935139f2e3f50848
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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