1,4-Dioxane → HCID 66599736, compound

HRID 1909013Notes

Reaction equation

HRID 1909013 reaction equation
COC(=O)[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1Br.[CH:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](B(O)O)=[CH:14][N:13]=1.[O-:25]P([O-])([O-])=O.[K+].[K+].[K+].O1C[CH2:37][O:36][CH2:35]C1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:35][O:36][C:37](=[O:25])[C:9]1[CH:4]=[CH:5][N:6]=[CH:7][C:8]=1[C:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 3761204Isoquinoline-4-boronic acidHCID 12349191Methyl 2-bromopyridine-3-carboxylate

Product 1

HCID 66599736HCID 66599736, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
70 °C

Procedure

To 2-bromonicotinic acid methyl ester (30 g, 111 mmol), isoquinoline-4-boronic acid (20 g, 92.6 mmol), 1,4-dioxane (770 mL) and 3M aqueous K3PO4 (35 mL, 105 mmol) were stirred together. The vessel was evacuated and flushed with nitrogen several times to remove oxygen. PdCl2(PPh3)2 (1.62 g, 1.85 mmol) was added and the vessel and the stirred mixture was heated at 70° C. overnight. The mixture was then cooled, concentrated in vacuo to 50% of original volume and filtered. The filtrate was concentrated in vacuo and the resulting residue stirred in butylmethylether (220 mL). The mixture was then filtered to remove solid. The filtrate was cooled in an ice bath and stirred for 1 hour after which time the product precipitated as a white solid. The product was collected and dried to give isoquinolin-4-yl-isonicotinic acid methyl ester (4.97 g, 16%) (combined from two crops) [M+H]+:264.7.

Workup

  1. customThe vessel was evacuated
  2. customflushed with nitrogen several times
  3. customto remove oxygen
  4. temperatureThe mixture was then cooled
  5. concentrationconcentrated in vacuo to 50% of original volume
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. filtrationThe mixture was then filtered
  9. customto remove solid
  10. temperatureThe filtrate was cooled in an ice bath
  11. stirringstirred for 1 hour after which time the product
  12. customprecipitated as a white solid
  13. customThe product was collected
  14. customdried

Sources & evidence

ORD record
ord-39e1f9c589f94bcdaee081b2bb809424
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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