Dimethylformamide → HCID 178522916, compound

HRID 2290027Notes

Reaction equation

HRID 2290027 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18](I)=[CH:17][C:16]=3[F:24])=[O:11])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:54][N:55]([CH:57]=[O:58])[CH3:56].N1C[CH2:63][O:62][CH2:61]C1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18]([C:57]([N:55]2[CH2:56][CH2:63][O:62][CH2:61][CH2:54]2)=[O:58])=[CH:17][C:16]=3[F:24])=[O:11])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8083MorpholineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 178522917HCID 178522917, compound

Product 1

HCID 178522916HCID 178522916, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To a pressure tube containing N-[(4-chlorophenyl)methyl]-8-fluoro-4-hydroxy-6-iodo-3-quinolinecarboxamide of Example No. 5 (0.23 g), palladium (II) acetate (12 mg), and 1,3-bis(diphenylphosphino)propane (20 mg) is added DMF (5 mL), triethylamine (0.14 mL) and morpholine (0.13 mL). The reaction mixture is placed under an atmosphere of carbon monoxide gas, then tightly sealed and heated at 60° C. overnight. The reaction is cooled to room temperature and concentrated under reduced pressure. The residue is partioned between dichloromethane and aqueous phosphate buffer (0.1M, pH=4). The organic phase is washed with aqueous phosphate buffer (0.1M, pH=10), brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue is chromatographed on silica eluting with 2% MeOH:CH2Cl2 to 8% MeOH:CH2Cl2. The product-containing fractions are evaporated to give 0.13 g of the title compound as a tan solid.

Workup

  1. customtightly sealed
  2. temperatureThe reaction is cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. washThe organic phase is washed with aqueous phosphate buffer (0.1M, pH=10), brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed on silica eluting with 2% MeOH
  9. customThe product-containing fractions are evaporated

Sources & evidence

ORD record
ord-1ca889433dbb48b186f2d559a5b4d4d3
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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