Sodium Carbonate → HCID 18407054, compound

HRID 1016633Notes

Reaction equation

HRID 1016633 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](I)[C:5]([NH2:8])=[N:6][CH:7]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]#[C:18][CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:18]([CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])=[C:17]([C:14]3[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 11776Triphenylphosphine2×HCID 433294Lithium ChlorideHCID 110760102-Amino-5-chloro-3-iodopyridineHCID 18407038HCID 18407038, compound

Product 1

HCID 18407054HCID 18407054, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-chloro-3-iodo-2-pyridinamine (Description 3, 2.31 g, 9.1 mmol), methyl 5-(4-chlorophenyl)-4-pentynoate (Description 2, 3.03 g, 13.6 mmol), triphenylphosphine (126 mg, 0.48 mmol), lithium chloride (385 mg, 9.1 mmol) and sodium carbonate (4.82, 45.5 mmol) in dimethylformamide (75 mL) was degassed with bubbling nitrogen, then palladium (II) acetate (102 mg, 0.45 mmol) was added and the mixture was stirred at 100° C. for 18 h. The mixture was cooled and further triphenylphosphine (126 mg, 0.48 mmol) and palladium (II) acetate (102 mg, 0.45 mmol) were added. The mixture was degassed with bubbling nitrogen and stirred at 100° C. for 6 h. The mixture was poured into saturated aqueous ammonium chloride and water and extracted with ethyl acetate. The combined organic fractions were washed with water and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (90:10 increasing to 75:25), to give the title compound (530 mg, 17%). 1H NMR (360 MHz, CDCl3) δ 10.90 (1H, br s), 8.10 (1H, d, J 2.2 Hz), 7.92 (1H, d, J 2.2 Hz), 7.60-7.52 (4H, m), 3.64 (3H, s), 3.19 (2H, t, J 7.9 Hz), and 2.65 (2H, t, J 7.9 Hz).

Workup

  1. customwas degassed with bubbling nitrogen
  2. temperatureThe mixture was cooled
  3. customThe mixture was degassed with bubbling nitrogen
  4. stirringstirred at 100° C. for 6 h
  5. additionThe mixture was poured into saturated aqueous ammonium chloride and water
  6. extractionextracted with ethyl acetate
  7. washThe combined organic fractions were washed with water and brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by flash column chromatography on silica gel
  11. washeluting with isohexane/EtOAc (90:10 increasing to 75:25)

Sources & evidence

ORD record
ord-39ce004106d44e25b0e9071cc9c0ab81
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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