Potassium Carbonate → HCID 70976664, compound

HRID 572341Notes

Reaction equation

HRID 572341 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][CH2:41][C:42]([OH:44])=[O:43])=[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][CH2:41][C:42]([OH:44])=[O:43])=[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 27356093-(4-Bromophenyl)propionic acidHCID 70976772HCID 70976772, compound

Product 1

HCID 70976664HCID 70976664, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °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) (382 mg, 0.884 mmol) and 3-(4-bromophenyl)propanoic acid (243 mg, 1.060 mmol) in toluene (6 mL) and ethanol (6 mL) were successively added tetrakis(triphenylphosphine)palladium(0) (102 mg, 0.088 mmol) and potassium carbonate (366 mg, 2.65 mmol). The resulting mixture was stirred at 80° C. for 2 h, then partitioned between water and EtOAc. 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 crude residue was purified by flash chromatography on silica gel (25 g), eluting with EtOAc in cyclohexane (10-70%). The appropriate fractions were combined and concentrated under reduced pressure to give 3-(4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)propanoic acid (209 mg, 52%) as a white solid. LCMS (Formate, 2 min), Rt=0.91 min, MH+=455.

Workup

  1. custompartitioned between water and EtOAc
  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 crude residue was purified by flash chromatography on silica gel (25 g)
  9. washeluting with EtOAc in cyclohexane (10-70%)
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d128ba5bbde347f0b3122321d456c330
Source dataset
uspto-grants-2015_05
Patent number
US09029395B2

Reaction notes

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