Phenol → 2,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one

HRID 600385Notes

Reaction equation

HRID 600385 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:5]2=[N:6][CH:7]=1.[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1N(C)C)(C)(C)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:13][C:12]([CH3:15])([CH3:14])[C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([O:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:3]=2)[N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:9]=1)=[O:16]

Participants

7

Reactant 4

HCID 996PhenolHCID 62657Potassium Phosphate, TribasicHCID 27349362-Di-tert-butylphosphino-2'-(N,N-dimethylamino)biphenylHCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

Product 1

HCID 578310492,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-oneYield 62.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.051 g, 0.12 mmol), phenol (0.017 g, 0.18 mmol), potassium phosphate (0.056 g, 0.26 mmol), 2-di-tert-butylphosphino-2′-(N,N-dimethylamino)biphenyl (0.0041 g, 0.012 mmol) and Pd(OAc)2 (0.002 g, 0.009 mmol) in 1 mL of toluene was stirred at 100° C. for 13 h, then at 150° C. for 4 h. The resulting dark orange mixture was partitioned between 10 mL of ethyl acetate and 10 mL of water. The organic layer was dried over MgSO4, filtered and concentrated to an orange oil. Column chromatography (0-20% EtOAc/hexanes) afforded 0.032 g (62%) of impure 2,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one as a yellow oil, which was used without further purification.

Workup

  1. waitat 150° C. for 4 h
  2. customThe resulting dark orange mixture was partitioned between 10 mL of ethyl acetate and 10 mL of water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an orange oil

Sources & evidence

ORD record
ord-efb3b03f13664245898e361fe81a4d0e
Source dataset
uspto-grants-2011_03
Patent number
US07902197B2

Reaction notes

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