Dimethylformamide → HCID 118093617, compound

HRID 1520100Notes

Reaction equation

HRID 1520100 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][S:17]([N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:19])=[O:18])=[CH:12][CH:11]=2)[CH:3]=1.[CH3:29][N:30](C=O)C>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.[C-]#N.[Zn+2].[C-]#N>[C:29]([C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][S:17]([N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:19])=[O:18])=[CH:12][CH:11]=2)[CH:3]=1)#[N:30]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 118093611HCID 118093611, compound

Product 1

HCID 118093617HCID 118093617, compoundYield 80.9%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

Under an atmosphere of nitrogen, combine tert-butyl N-[[4-(6-chloro-2-methyl-pyrimidin-4-y)oxyphenyl]methylsulfonyl]-N-methyl-carbamate (2.24 g, 3.4 mmol), DMF (2 mL), tetrakis(triphenylphosphine)palladium (1.9 g, 1.7 mmol), and zinc cyanide (2.0 g, 16.8 mmol). Heat the mixture to 90° C. and stir for 3 hours. Quench the reaction with water and sodium hydroxide. Extract the mixture with EtOAc; wash the EtOAc extract(s) with brine; dry over magnesium sulfate; filter and concentrate the filtrate under reduced pressure to provide a residue. Purify the title compound via flash column chromatography using 80 g of silica gel, and eluting with a 0-55% gradient of EtOAc in hexanes. Evaporate the relevant fractions to provide the title compound as a yellow oil (1.2 g, 80.9%). MS (m/z): 419 (M+1).

Workup

  1. customQuench
  2. customthe reaction with water and sodium hydroxide
  3. extractionExtract the mixture with EtOAc
  4. washwash the EtOAc
  5. extractionextract(s) with brine
  6. dry with materialdry over magnesium sulfate
  7. filtrationfilter
  8. concentrationconcentrate the filtrate under reduced pressure
  9. customto provide a residue
  10. customPurify the title compound via flash column chromatography
  11. washeluting with a 0-55% gradient of EtOAc in hexanes
  12. customEvaporate the relevant fractions

Sources & evidence

ORD record
ord-97a16ed44d3b4d458ac03e6149732d93
Source dataset
uspto-grants-2015_07
Patent number
US09073901B2

Reaction notes

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