Potassium Carbonate → Methyl 4-(2-fluoro-4-methoxyphenyl)-7-[1-(2-methylpyrimidin-5-yl)propan-2-yl]quinoline-2-carboxylate

HRID 922814Notes

Reaction equation

HRID 922814 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[C:19]2[C:14](=[CH:15][C:16]([C:20]([CH3:22])=[CH2:21])=[CH:17][CH:18]=2)[N:13]=[C:12]([C:23]([O:25][CH3:26])=[O:24])[CH:11]=1.B1C2CCCC1CCC2.Br[C:37]1[CH:38]=[N:39][C:40]([CH3:43])=[N:41][CH:42]=1.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.[Cl-].[Na+].O.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].CCOC(C)=O.O>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[C:19]2[C:14](=[CH:15][C:16]([CH:20]([CH3:22])[CH2:21][C:37]3[CH:38]=[N:39][C:40]([CH3:43])=[N:41][CH:42]=3)=[CH:17][CH:18]=2)[N:13]=[C:12]([C:23]([O:25][CH3:26])=[O:24])[CH:11]=1

Participants

11

Reactant 5

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 143877445-Bromo-2-methylpyrimidineHCID 89543695Methyl 4-(2-fluoro-4-methoxyphenyl)-7-(prop-1-en-2-yl)quinoline-2-carboxylate

Product 1

HCID 89543793Methyl 4-(2-fluoro-4-methoxyphenyl)-7-[1-(2-methylpyrimidin-5-yl)propan-2-yl]quinoline-2-carboxylateYield 17.62%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 4-(2-fluoro-4-methoxyphenyl)-7-(prop-1-en-2-yl)quinoline-2-carboxylate (1.5 g, 4.27 mmol) was dissolved in THF (7.8 ml), heated to 60° C. and then added 9-BBN (0.5M THF, 10.7 ml, 5.35 mmol) dropwise over 5 minutes. After 1 hour, allowed to cool to ambient. Added 5-bromo-2-methylpyrimidine (0.886 g, 5.12 mmol), Pd2(dba)3 (0.195 g, 0.213 mmol), butyldi-1-adamantylphosphine (0.153 g, 0.427 mmol), potassium carbonate (2.360 g, 17.08 mmol) and water (0.776 ml), degassed 5 minutes with nitrogen and then heated to 90° C. in a sealed tube for 30 minutes. The reaction was allowed to cool to ambient temperature. To the mixture was added brine and then EtOAc. The organic portion was collected, dried (MgSO4) and then concentrated. The residue was purified by column chromatography on silica gel, eluting with CHCl3 to 70:25:5 CHCl3/EtOAc/MeOH to afford methyl 4-(2-fluoro-4-methoxyphenyl)-7-[1-(2-methylpyrimidin-5-yl)propan-2-yl]quinoline-2-carboxylate (335 mg, 0.752 mmol, 17.62% yield) as an orange oil.

Workup

  1. temperatureto cool to ambient
  2. temperatureheated to 90° C. in a sealed tube for 30 minutes
  3. temperatureto cool to ambient temperature
  4. customThe organic portion was collected
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluting with CHCl3 to 70:25:5 CHCl3/EtOAc/MeOH

Sources & evidence

ORD record
ord-d2781b01549f46e1be92400831c9b7bc
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

Loading…