Toluene → HCID 70980749, compound

HRID 572337Notes

Reaction equation

HRID 572337 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:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][N:35]=1.[C:44](=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>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(O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:34]3[CH:43]=[CH:42][C:37]([C:38]([O:40][CH2:41][CH3:44])=[O:39])=[CH:36][N: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 4

HCID 1140TolueneHCID 11430Potassium Carbonate2×HCID 13349623Methyl 6-bromopyridine-3-carboxylate2×HCID 70976772HCID 70976772, compound

Product 1

HCID 70980749HCID 70980749, compoundYield 71.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

To a flask charged with 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) (800 mg, 1.850 mmol), methyl 6-bromonicotinate (440 mg, 2.036 mmol), potassium carbonate (767 mg, 5.55 mmol) and tetrakis(triphenylphosphine)palladium(0) (214 mg, 0.185 mmol) were added toluene (8 mL) and ethanol (8 mL). The resulting mixture was stirred at 90° C. under nitrogen for 3 h at which point portions of potassium carbonate (384 mg) tetrakis(triphenylphosphine)palladium(0) (107 mg) and methyl 6-bromonicotinate (220 mg) were added and the reaction mixture stirring continued for 5 h. The mixture was then cooled to room temperature and concentrated in vacuo. The residue was partitioned between EtOAc and water. The phases were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography [25 g column, EtOAc/Hexanes gradient] to give ethyl 6-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate (600 mg, 1.317 mmol, 71.2% yield) as a white foam. LCMS (HpH, 2 min), Rt=1.07 min, MH+=456.

Workup

  1. additionwere added
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between EtOAc and water
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography [25 g column, EtOAc/Hexanes gradient]

Sources & evidence

ORD record
ord-f34e5df5c77e450fb34eab3307b27293
Source dataset
uspto-grants-2015_05
Patent number
US09029395B2

Reaction notes

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