Potassium Acetate → 4-Chloro-2-[(1R,11S)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde

HRID 592740Notes

Reaction equation

HRID 592740 reaction equation
[C@@H:1]12[CH2:14][C@@H:11]([CH2:12][CH2:13]1)[C:10]1[CH:9]=[C:8]3[N:3]([CH2:4][CH2:5][NH:6][C:7]3=[O:15])[C:2]2=1.Br[C:17]1[N:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:18]=1[CH:19]=[O:20].C([O-])(=O)C.[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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].O1CCOCC1>[Cl:25][C:21]1[CH:22]=[CH:23][N:24]=[C:17]([N:6]2[C:7](=[O:15])[C:8]3[N:3]([C:2]4[C@H:1]5[CH2:14][C@@H:11]([C:10]=4[CH:9]=3)[CH2:12][CH2:13]5)[CH2:4][CH2:5]2)[C:18]=1[CH:19]=[O:20]

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866839142-Bromo-4-chloropyridine-3-carbaldehydeHCID 86684302(1S,11R)-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-7-one

Product 1

HCID 866843014-Chloro-2-[(1R,11S)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehydeYield 59.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (30 mL), (1S,11R)-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-7-one 170a (400 mg, 2.0 mmol), 2-bromo-4-chloronicotinaldehyde 103a (1.30 g, 6.0 mmol), and potassium acetate (390 mg, 4.0 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, Xantphos (110 mg, 0.20 mmol) and tris(dibenzylideneacetone)dipalladium(0) (180 mg, 0.20 mmol) were added, and the reaction mixture was heated at 80° C. for 10 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (30 mL). The aqueous layer was separated and extracted with ethyl acetate (3×30 mL). The combined organic layer was washed with brine (20 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 2:1 petroleum ether/ethyl acetate to afford 170b (405 mg, 59%) as a yellow solid. MS-ESI: [M+H]+ 342.2

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (30 mL)
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate (3×30 mL)
  8. washThe combined organic layer was washed with brine (20 mL)
  9. dry with materialdried over sodium sulfate
  10. customThe drying agent was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica-gel column chromatography
  13. washeluting with 2:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-82dab269a220413fb14dedc5dfd4f510
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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