Phenol → 1-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenoxy-phthalazine

HRID 2268890Notes

Reaction equation

HRID 2268890 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Cl[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=2)[C:14]([CH2:23][C:24]2[C:29]([Cl:30])=[CH:28][N:27]=[CH:26][C:25]=2[Cl:31])=[N:13][N:12]=1>CN(C=O)C>[Cl:31][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([Cl:30])[C:24]=1[CH2:23][C:14]1[C:15]2[C:20](=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:11]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:12][N:13]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 186292104-Chloro-1-[(3,5-dichloropyridin-4-yl)methyl]-6-methoxyphthalazine

Product 1

HCID 183324591-(3,5-Dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenoxy-phthalazineYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of DMF (15 ml), phenol (0.53 g, 5.64 mmoles) and NaH (4.23 mmoles) was stirred under dry N2 at room temperature. After 15 minutes 4-chloro-1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazine (0.5 g, 1.41 mmoles), prepared as described in example 45, was dropped and the temperature brought to 100° C. After 20 hours the mixture was partitioned between water and CH2Cl2. The organic phase was washed with water, anhydrified and concentrated to give a residue which was triturated in ethyl ether. The insoluble was flash chromatographed (eluent: hexane/ethyl acetate 7:3) to give a solid which was crystallised from isopropyl ether (15 ml) and yielded 0.25 g of the title compound (yield: 49%). m.p.: 130-132° C.

Workup

  1. customprepared
  2. additionwas dropped
  3. custombrought to 100° C
  4. customAfter 20 hours the mixture was partitioned between water and CH2Cl2
  5. washThe organic phase was washed with water, anhydrified
  6. concentrationconcentrated
  7. customto give a residue which
  8. customwas triturated in ethyl ether
  9. customchromatographed (eluent: hexane/ethyl acetate 7:3)
  10. customto give a solid which
  11. customwas crystallised from isopropyl ether (15 ml)

Sources & evidence

ORD record
ord-85ce08301438452383f63a5ed3fa4bfd
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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