HCID 9908871, compound → 1-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenyl-phthalazine

HRID 2297430Notes

Reaction equation

HRID 2297430 reaction equation
[C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH3:20])[CH:17]=2)[C:12]([CH2:21][C:22]2[C:27]([Cl:28])=[CH:26][N:25]=[CH:24][C:23]=2[Cl:29])=[N:11][N:10]=1>C1COCC1.[Cl-].[Cl-].[Zn+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:29][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([Cl:28])[C:22]=1[CH2:21][C:12]1[C:13]2[C:18](=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C:9]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:10][N:11]=1

Participants

7

Reactant 2

HCID 9908871HCID 9908871, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 99525921-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenyl-phthalazineYield 55%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

ZnCl2 (2.04 g, 15 mmoles) under N2 in THF (100 ml) was added with phenyl lithium (7.5 ml, 15 mmoles; 2M in cyclohexane/ethyl ether 7:3) at 0-4° C. The mixture was stirred at room temperature for 1 hour. 4-Bromo-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazine (3 g, 7.5 mmoles), prepared as described in example 46, palladium acetate (0.034 g, 0.15 mmole) and triphenylphosphine (0.08 g, 0.3 mmole) were added and the mixture was refluxed for 24 hours, cooled and extracted with a saturated solution of NHCl. The organic phase was extracted again with ethyl acetate, discoloured with charcoal, anhydrified and concentrated to give a solid which was flash chromatographed (eluent: petrolatum/ethyl acetate 6:4). The resultant solid was triturated in ethyl ether, crystallised from acetonitrile (80 ml) and dried overnight to give 1.44 g of the title compound (yield: 55%).

Workup

  1. additionwere added
  2. temperaturethe mixture was refluxed for 24 hours
  3. temperaturecooled
  4. extractionextracted with a saturated solution of NHCl
  5. extractionThe organic phase was extracted again with ethyl acetate
  6. concentrationconcentrated
  7. customto give a solid which
  8. customchromatographed (eluent: petrolatum/ethyl acetate 6:4)
  9. customThe resultant solid was triturated in ethyl ether
  10. customcrystallised from acetonitrile (80 ml)
  11. customdried overnight

Sources & evidence

ORD record
ord-81104d5b829f40f9b1ee4c9146339a7e
Source dataset
uspto-grants-2002_12
Patent number
US06492360B1

Reaction notes

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