Hexane → 1-(tert-Butyl-dimethyl-silanyl)-5-(3-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine

HRID 493149Notes

Reaction equation

HRID 493149 reaction equation
[Li]CCCC.CCCCCC.[F:12][C:13]1[CH:14]=[C:15]([C:19]2[CH:20]=[C:21]3[CH:27]=[CH:26][NH:25][C:22]3=[N:23][CH:24]=2)[CH:16]=[CH:17][CH:18]=1.[CH3:28][C:29]([Si:32](Cl)([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C1COCC1.CN(C1C=CN=CC=1)C>[C:29]([Si:32]([CH3:34])([CH3:33])[N:25]1[C:22]2=[N:23][CH:24]=[C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([F:12])[CH:14]=3)[CH:20]=[C:21]2[CH:27]=[CH:26]1)([CH3:31])([CH3:30])[CH3:28]

Participants

7

Reactant 4

HCID 8058HexaneHCID 28928tert-Butyldimethylsilyl chlorideHCID 103079645-(3-Fluorophenyl)-1h-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 497590641-(tert-Butyl-dimethyl-silanyl)-5-(3-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridineYield 81%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

2.5 M solution of n-BuLi in hexane (13.7 mL, 34.3 mmol) was added dropwise to a stirred and cooled (−78° C.) solution of azaindole 7 (6.04 g, 28.5 mmol) in THF (30 mL). After the mixture was stirred for 10 min at −78° C., DMAP (66 mg, 0.54 mmol) was added, followed by a solution of TBSCl (5.14 g, 34.1 mmol) in THF (2.5 mL). The mixture was stirred at −78° C. for 1 h. Cooling bath was removed, the mixture was stirred at r.t. for 3 days, and separated between AcOEt:saturated aqueous NaHCO3 solution. The aqueous layer was extracted with AcOEt (3×). Combined organic solutions were dried (MgSO4), concentrated, and separated by means of SGC with hexane:benzene as eluent in gradient (up to 15% benzene) to afford 8 (7.50 g, 81%) as white solid. 1H NMR (400 MHz, CDCl3) δ 0.67 (s, 6H), 0.96 (s, 9H), 6.59 (d, J=3.5 Hz, 1H), 6.99-7.07 (m, 1H), 7.29 (d, J=3.5 Hz, 1H), 7.33 (ddd, J=10.9, 3.0, 1.7 Hz, 1H), 7.38-7.44 (m, 2H), 8.04 (d, J=2.3 Hz, 1H), 8.51 (d, J=2.3 Hz, 1H).

Workup

  1. stirringAfter the mixture was stirred for 10 min at −78° C.
  2. stirringThe mixture was stirred at −78° C. for 1 h
  3. temperatureCooling bath
  4. customwas removed
  5. stirringthe mixture was stirred at r.t. for 3 days
  6. customseparated between AcOEt
  7. extractionThe aqueous layer was extracted with AcOEt (3×)
  8. dry with materialCombined organic solutions were dried (MgSO4)
  9. concentrationconcentrated
  10. customseparated by means of SGC with hexane

Sources & evidence

ORD record
ord-fe9e310605f343ed9951961ef573d7bd
Source dataset
uspto-grants-2009_05
Patent number
US07534800B2

Reaction notes

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