Toluene → HCID 70976544, compound

HRID 882235Notes

Reaction equation

HRID 882235 reaction equation
[CH3:1][C@H:2]1[CH2:11][C@@H:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][N:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7](B3OC(C)(C)C(C)(C)O3)[CH:8]=2)[N:3]1[C:31](=[O:33])[CH3:32].Br[C:35]1[CH:44]=[CH:43][C:38]([C:39]([O:41][CH3:42])=[O:40])=[CH:37][N:36]=1.[C:45](=O)([O-])[O-].[K+].[K+].C1(C)C=CC=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].C(O)C>[C:31]([N:3]1[C:4]2[C:9](=[CH:8][C:7]([C:35]3[CH:44]=[CH:43][C:38]([C:39]([O:41][CH2:42][CH3:45])=[O:40])=[CH:37][N:36]=3)=[CH:6][CH:5]=2)[C@H:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][N:14]=2)[CH2:11][C@@H:2]1[CH3:1])(=[O:33])[CH3:32]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium Carbonate2×HCID 13349623Methyl 6-bromopyridine-3-carboxylate2×HCID 70976484HCID 70976484, compound

Product 1

HCID 70976544HCID 70976544, compoundYield 68.3%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst2×HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

to a flask charged with 1-((2S,4R)-2-methyl-4-((5-nitropyridin-2-yl)amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 24)(1.03 g, 2.277 mmol), methyl 6-bromonicotinate (0.541 g, 2.505 mmol), potassium carbonate (0.944 g, 6.83 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.263 g, 0.228 mmol) was added a previously degassed mixture of toluene (10 mL) and ethanol (10 mL). The resulting mixture was stirred at 90° C. under nitrogen. After 3 h, further portions of methyl 6-bromonicotinate (0.271 g, 1.252 mmol), potassium carbonate (0.472 g, 3.42 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.132 g, 0.114 mmol) were added and reaction mixture heated for a further 4 h. The reaction was cooled to room temperature and concentrated in vacuo. The crude residue was partitioned between EtOAc and water, the phases separated and aqueous phase extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by chromatography, eluting with an EtOAc/hexanes gradient gave ethyl 6-((2S,4R)-1-acetyl-2-methyl-4-((5-nitropyridin-2-yl)amino)-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate (740 mg, 1.556 mmol, 68.3% yield) as a yellow foam.

Workup

  1. additionwas added
  2. customreaction mixture
  3. temperatureheated for a further 4 h
  4. temperatureThe reaction was cooled to room temperature
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was partitioned between EtOAc and water
  7. customthe phases separated
  8. extractionaqueous phase extracted with EtOAc
  9. washThe combined organic phases were washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customPurification of the residue by chromatography
  13. washeluting with an EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-4ef03655b5bc46b78e7bda1f443374d9
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

Loading…