Dimethylformamide → 1-(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}propyl)-5-isoquinolinecarbonitrile

HRID 2192470Notes

Reaction equation

HRID 2192470 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH2:12][CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[CH3:23][N:24](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][C:19]([Si:16]([CH3:18])([CH3:17])[O:15][CH2:14][CH2:13][CH2:12][C:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:2]([C:23]#[N:24])[C:3]=2[CH:4]=[CH:5][N:6]=1)([CH3:22])[CH3:21]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 581498995-Bromo-1-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)isoquinoline

Product 1

HCID 581498881-(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}propyl)-5-isoquinolinecarbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A microwave vial was charged with 5-bromo-1-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)isoquinoline (D11; 640 mg, 1.68 mmol), dry, degassed N,N-dimethylformamide (DMF) (8 ml), zinc cyanide (217 mg, 1.85 mmol) and tetrakis(triphenylphosphine)palladium(0) (194 mg, 0.168 mmol). The reaction vessel was sealed and heated using microwave irradiation to 120° C. for 60 min. After cooling, the mixture was diluted with ethyl acetate, the organic layers partitioned with water (×3) and the aqueous layer discarded. The organic layers were passed through a hydrophobic frit before being concentrated in vacuo. The resultant yellow oil was purified by flash column chromatography on silica using 2% to 20% ethyl acetate in cyclohexane as eluent. The relevant fractions were pooled and concentrated in vacuo to give the title compound as a yellow oil (417 mg).

Workup

  1. customdry
  2. customThe reaction vessel was sealed
  3. temperatureheated
  4. custommicrowave irradiation to 120° C. for 60 min
  5. temperatureAfter cooling
  6. customthe organic layers partitioned with water (×3)
  7. concentrationbefore being concentrated in vacuo
  8. customThe resultant yellow oil was purified by flash column chromatography on silica using 2% to 20% ethyl acetate in cyclohexane as eluent
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4008526604074efdbcee16631abba4b1
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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