Nitrogen → Methyl 7-[2-(6-cyanopyridin-3-yl)ethyl]-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate

HRID 922811Notes

Reaction equation

HRID 922811 reaction equation
[CH:1]([C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=3[F:25])=[CH:8][C:9]([C:13]([O:15][CH3:16])=[O:14])=[N:10]2)=[CH:5][CH:4]=1)=[CH2:2].B1C2CCCC1CCC2.Br[C:36]1[CH:37]=[CH:38][C:39]([C:42]#[N:43])=[N:40][CH:41]=1.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.C(=O)([O-])[O-].[K+].[K+].N#N>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>[C:42]([C:39]1[N:40]=[CH:41][C:36]([CH2:2][CH2:1][C:3]2[CH:12]=[C:11]3[C:6]([C:7]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=4[F:25])=[CH:8][C:9]([C:13]([O:15][CH3:16])=[O:14])=[N:10]3)=[CH:5][CH:4]=2)=[CH:37][CH:38]=1)#[N:43]

Participants

12

Reactant 6

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 8171545-Bromopyridine-2-carbonitrileHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 89543754Methyl 4-(2-fluoro-4-methoxyphenyl)-7-vinylquinoline-2-carboxylate

Product 1

HCID 89543747Methyl 7-[2-(6-cyanopyridin-3-yl)ethyl]-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylateYield 48.9%

Reagents, catalysts & solvents 5

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

Conditions

Temperature
60 °C

Procedure

Methyl 7-ethenyl-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (250 mg, 0.741 mmol) was dissolved in THF (1.3 ml), heated to 60° C. and then added 9-BBN (0.5M THF, 1.85 ml, 0.93 mmol) dropwise over 5 minutes. After 1 hour, allowed to cool to ambient. Added 5-bromopyridine-2-carbonitrile (203 mg, 1.112 mmol), Pd2(dba)3 (33.9 mg, 0.037 mmol), butyldi-1-adamantylphosphine (26.6 mg, 0.074 mmol), potassium carbonate (410 mg, 2.96 mmol) and water (135 degassed 5 minutes with N2 and then heated to 90° C. in a sealed tube for 30 minutes. Reaction proceeded, allowed to cool to ambient. Added brine and then EtOAc. The organic portion was collected, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica gel, eluting with hexanes to EtOAc to afford methyl 7-[2-(6-cyanopyridin-3-yl)ethyl]-4-(2-fluoro-4-methoxyphenyl)quinoline-2-carboxylate (160 mg, 0.362 mmol, 48.9% yield) as an orange oil.

Workup

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

Sources & evidence

ORD record
ord-12de72b1f93c40a2920f82f43e89bfbc
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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