HCID 9908871, compound → 1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxy-4-phenylphthalazine

HRID 2268859Notes

Reaction equation

HRID 2268859 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-dichloropyridin-4-yl)methyl]-6-methoxy-4-phenylphthalazineYield 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-1-(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 NH4Cl. 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 NH4Cl
  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-5a6cb434328b480c967802b68a3d44e2
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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