Hydrochloric Acid → 5-(Pyridin-4-yl)-2-[2-(quinolin-2-yl)ethyl]phthalazin-1(2H)-one hydrochloride

HRID 920925Notes

Reaction equation

HRID 920925 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[N:5][N:6]([CH2:13][CH2:14][C:15]1[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=1)[C:7]2=[O:12].[N:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].[ClH:40]>C(O)C.C1(C)C=CC=CC=1.CC(=O)OCC.C(Cl)Cl.CO>[ClH:40].[N:25]1[CH:30]=[CH:29][C:28]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[N:5][N:6]([CH2:13][CH2:14][C:15]2[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=2)[C:7]3=[O:12])=[CH:27][CH:26]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 866831355-Bromo-2-[2-(quinolin-2-yl)ethyl]phthalazin-1(2H)-one

Product 1

HCID 866831375-(Pyridin-4-yl)-2-[2-(quinolin-2-yl)ethyl]phthalazin-1(2H)-one hydrochlorideYield 72%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
130 °C

Procedure

A reaction tube was charged with a solution of 5-bromo-2-[2-(quinolin-2-yl)ethyl]phthalazin-1(2H)-one (70 mg, 0.184 mmol) in 1.5 mL of ethanol and 1.5 mL of toluene under argon. To this suspension, pyridin-4-ylboronic acid (22.63 mg, 0.184 mmol) and a 2M solution of Na2CO3 (39.2 mg, 0.369 mmol) were added. Then, tetrakis-(triphenylphoshine)palladium (21.27 mg, 0.018 mmol) was added. The reaction mixture was heated in a Biotage microwave at about 130° C. for about 30 min. The reaction was monitored by TLC (DCM/methanol=9:1). After completion of the reaction, EA was added followed by the addition of 1 N HCl. The mixture was extracted twice with EtOAc. The organic layer was basified with NaHCO3 and extracted with brine. The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was dissolved in isopropanol. Isopropanol containing HCl was added. The precipitate was sucked off and recrystallized from hot isopropanol to give a bright gray solid (55 mg, 72.0%).

Workup

  1. additionwas added
  2. extractionThe mixture was extracted twice with EtOAc
  3. extractionextracted with brine
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe crude product was dissolved in isopropanol
  8. additionIsopropanol containing HCl
  9. additionwas added
  10. customrecrystallized from hot isopropanol

Sources & evidence

ORD record
ord-394c0540575d491f9aafbadfe6484e0f
Source dataset
uspto-grants-2016_03
Patent number
US09273068B2

Reaction notes

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