3-Pyridinemethanol → 1-(4-Chlorophenylamino)-4-(3-pyridylmethoxy)phthalazine

HRID 1070527Notes

Reaction equation

HRID 1070527 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[N:4][N:3]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][OH:27])[CH:21]=1.C1CCN2C(=NCCC2)CC1>>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([O:27][CH2:26][C:22]3[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=3)=[N:3][N:4]=2)=[CH:14][CH:15]=1

Participants

4

Reactant 3

HCID 75103-PyridinemethanolHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 120756491-Chloro-4-(4-chlorophenylamino)-phthalazine

Product 1

HCID 99508801-(4-Chlorophenylamino)-4-(3-pyridylmethoxy)phthalazineYield 56%

Procedure

A dry 50-mL round-bottomed flask was equipped with a stir bar and an argon inlet. The flask was charged with 1-chloro-4-(4-chlorophenylamino)-phthalazine (R. D. Haworth and S. Robinson, J. Chem. Soc. 1948, pp.777-782) (2.00 g; ˜6.12 mmol), 3-pyridyl-carbinol (Aldrich) (10.02 g, 91.85 mmol), and DBU (18.3 mL, ˜18.7 g, ˜123 mmol). The reaction was heated at 125 C for 28 h. The mixture was cooled to room temperature and distilled water (400 mL) was added with stirring. The aqueous phase was extracted with ethyl acetate (3×300 mL). The combined organics were dried (MgSO4) and concentrated to yield a tan solid, which was purified by silica gel chromatography (100% dichloromethane→50% acetone/dichloromethane) to give the clean desired compound as a white solid (1.24 g, 3.42 mmol; 56% yield). TLC (20% acetone/dichloromethane): Rf=0.48.

Workup

  1. customA dry 50-mL round-bottomed flask was equipped with a stir bar and an argon inlet
  2. temperatureThe reaction was heated at 125 C for 28 h
  3. distillationdistilled water (400 mL)
  4. additionwas added
  5. extractionThe aqueous phase was extracted with ethyl acetate (3×300 mL)
  6. dry with materialThe combined organics were dried (MgSO4)
  7. concentrationconcentrated
  8. customto yield a tan solid, which
  9. customwas purified by silica gel chromatography (100% dichloromethane→50% acetone/dichloromethane)

Sources & evidence

ORD record
ord-19aa84d564294230968104f47b928bf9
Source dataset
uspto-grants-2005_06
Patent number
US06903101B1

Reaction notes

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