Dimethylformamide → HCID 22335233, compound

HRID 586714Notes

Reaction equation

HRID 586714 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]=[C:13](Cl)[CH:12]=[CH:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Li+].[CH3:21][N:22](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]=[C:13]([C:21]#[N:22])[CH:12]=[CH:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 433294Lithium ChlorideHCID 162287476-Benzyl-2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine

Product 1

HCID 22335233HCID 22335233, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst3×

Conditions

Temperature
100 °C

Procedure

6-Benzyl-2-chloro-5,6,7,8-tetrahydro-[1,6]naphthyridine (129 mg, 0.5 mmol) (See Reference WO9830560 Example 33b) was added to zinc cyanide (58.7 mg, 0.5 mmol), lithium chloride (27 mg, 0.65 mmol) and tetrakis(triphenylphosphine)palladium (0) (35 mg, 0.03 mmol) in N,N-dimethylformamide (3 ml). The mixture was purged with argon and was heated at 100° C. for 17 hours. The reaction mixture was cooled to room temperature and a further quantity of tetrakis(triphenylphosphine)palladium (0) (35 mg, 0.03 mmol) was added and the mixture was heated at 125° C. for 3 hours. The reaction mixture was cooled to room temperature and a further quantity of tetrakis(triphenylphosphine)palladium (0) (35 mg, 0.03 mmol) was added and the mixture was heated at 125° C. for 3 hours. The reaction mixture was cooled to room temperature and was partitioned between ethyl acetate (40 ml) and water (40 ml). The phases were separated and the organic phase was washed with water (3×30 ml) dried over magnesium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using ethyl acetate in pentane as eluant (33:67) to give the title compound as a brown gum (97 mg).

Workup

  1. customThe mixture was purged with argon
  2. temperatureThe reaction mixture was cooled to room temperature
  3. temperaturethe mixture was heated at 125° C. for 3 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. temperaturethe mixture was heated at 125° C. for 3 hours
  6. temperatureThe reaction mixture was cooled to room temperature
  7. customwas partitioned between ethyl acetate (40 ml) and water (40 ml)
  8. customThe phases were separated
  9. washthe organic phase was washed with water (3×30 ml)
  10. dry with materialdried over magnesium sulphate
  11. customevaporated under reduced pressure
  12. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-2cab6c20059447128af231a092f394ae
Source dataset
uspto-grants-2005_08
Patent number
US06936619B2

Reaction notes

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