1-Chloro-4-(4-pyridinylmethyl)phthalazine → HCID 9931119, compound

HRID 1070534Notes

Reaction equation

HRID 1070534 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[N:4][N:3]=1.[NH2:19][C:20]1[CH:32]=[CH:31][C:23]([O:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)=[CH:22][CH:21]=1>C(O)CCC>[N:28]1[CH:27]=[CH:26][C:25]([O:24][C:23]2[CH:31]=[CH:32][C:20]([NH:19][C:2]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5]([CH2:12][C:13]4[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=4)=[N:4][N:3]=3)=[CH:21][CH:22]=2)=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 19446091-Chloro-4-(4-pyridinylmethyl)phthalazineHCID 115645894-(Pyridin-4-yloxy)aniline

Product 1

HCID 9931119HCID 9931119, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 1-chloro-4-(4-pyridylmethyl)phthalazine (for preparation see Novartis patent WO98135958, 11.02.98) (0.540 g, 2.11 mmol) and 4-(4-aminophenoxy)pyridine (1.18 g, 6.33 mmol) in anhydrous 1-butanol (8.4 mL) was stirred under argon at 130° C. for 18 h. The reaction mixture was quenched with saturated aqueous potassium carbonate (˜50 mL) and then extracted with dichloromethane (3×100 mL). The combined organic phases were dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography in 7:11:2 v/v acetone-dichloromethane-methanol provided the title compound as an oil (0.340 g, 0.84 mmol, 40% yield). 1H-NMR (DMSO-d6) 9.26 (s, 1H), 8.58 (d, J=8.3, 1H), 8.41 to 8.44 (m, 4H), 8.10 (d, J=8.2, 11H), 7.90 to 8.03 (m, 4H), 7.30 (d, J=5.9, 2H), 7.17 (d, J=9.2, 2H), 6.91 (d, J=5.8, 2H), 4.56 (s, 2H); MS ES 406 (M+H)+, calc. 405; TLC (1:7:12 v/v methanol-acetone-dichloromethane) Rf=0.08.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous potassium carbonate (˜50 mL)
  2. extractionextracted with dichloromethane (3×100 mL)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash column chromatography in 7:11:2 v/v acetone-dichloromethane-methanol

Sources & evidence

ORD record
ord-251ddc3aef3a46ac9d7c18d1b50e5792
Source dataset
uspto-grants-2005_06
Patent number
US06903101B1

Reaction notes

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