Potassium Carbonate → HCID 86709414, compound

HRID 882222Notes

Reaction equation

HRID 882222 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2].Br[C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:36][CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:34]3[CH:39]=[CH:38][C:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:36][CH:35]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 7020609Ethyl 2-(4-bromophenyl)acetateHCID 70976772HCID 70976772, compound

Product 1

HCID 86709414HCID 86709414, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-(((2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 5) (1.67 g, 3.86 mmol), ethyl 2-(4-bromophenyl)acetate (1.127 g, 4.64 mmol) and potassium carbonate (1.602 g, 11.59 mmol) in toluene (10 mL) and ethanol (10.0 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.446 g, 0.386 mmol) under nitrogen. The reaction mixture heated at 100° C. for 1 h, then partitioned between EtOAc and water. The layers were separated and the aqueous phase was extracted with EtOAc (×3). The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (25 g), eluting with an EtOAc/cyclohexane gradient (10 to 80%). The appropriate fractions were combined and concentrated in vacuo to give ethyl 2-(4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetate (752 mg, 42%) as a viscous colourless oil. LCMS (Formate, 2 min), Rt=1.10 min, MH+=469.

Workup

  1. custompartitioned between EtOAc and water
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (25 g)
  9. washeluting with an EtOAc/cyclohexane gradient (10 to 80%)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26b3ab64469e47e9aa6f8451ed99e0d0
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

Loading…