7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine → 4-hydroxy-3,3-dimethyl-4-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-butyronitrile

HRID 1677523Notes

Reaction equation

HRID 1677523 reaction equation
[Cl-].[Li+].C([Mg]Cl)CC.I[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=3)[N:16]=2)[N:11]([Si:30]([CH:37]([CH3:39])[CH3:38])([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])[CH3:32])[CH:10]=1.[CH3:40][C:41]([CH3:47])([CH:45]=[O:46])[CH2:42][C:43]#[N:44]>O1CCCC1>[OH:46][CH:45]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=3)[N:16]=2)[N:11]([Si:30]([CH:37]([CH3:39])[CH3:38])([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])[CH3:32])[CH:10]=1)[C:41]([CH3:47])([CH3:40])[CH2:42][C:43]#[N:44]

Participants

5

Reactant 3

HCID 595405257-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazineHCID 595406093,3-Dimethyl-4-oxo-butyronitrileHCID 178455856HCID 178455856, compound

Product 1

HCID 595407864-hydroxy-3,3-dimethyl-4-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-butyronitrileYield 62.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Propyl magnesium chloride lithium chloride (1.3 M solution in THF, 1.7 mL, 2.2 mmol) was added to 3 mL of tetrahydrofuran cooled to −78° C. A solution of 7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine (0.250 g, 0.440 mmol) in 2 mL of tetrahydrofuran was slowly added, and the mixture was stirred at −78° C. for 2 h. A solution of 3,3-dimethyl-4-oxo-butyronitrile (0.241 g, 2.17 mmol) in 2 mL of tetrahydrofuran was added dropwise, and the mixture was stirred, allowing to slowly warm to RT, for 19 h, then quenched with 100 mL of a sat. aq. NaHCO3 solution. The resulting mixture was extracted with 100 mL of ethyl acetate, and the organic layer was dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0→50% EtOAc/hexanes) afforded 0.152 g (62%) of 4-hydroxy-3,3-dimethyl-4-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-butyronitrile as a yellow oil.

Workup

  1. stirringthe mixture was stirred
  2. temperatureto slowly warm to RT, for 19 h
  3. customquenched with 100 mL of a sat. aq. NaHCO3 solution
  4. extractionThe resulting mixture was extracted with 100 mL of ethyl acetate
  5. dry with materialthe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-645855efac8f4609b9fde4c6afcd4d1a
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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