Hydrogen Peroxide → HCID 9808717, compound

HRID 1070526Notes

Reaction equation

HRID 1070526 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20](C)[CH:19]=3)=[N:9][N:8]=2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.OO.[CH3:34][NH:35][CH:36]=[O:37]>O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2]>[CH3:34][NH:35][C:36]([C:20]1[CH:19]=[C:18]([CH2:17][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:7]([NH:6][C:5]3[CH:25]=[CH:26][C:2]([Cl:1])=[CH:3][CH:4]=3)=[N:8][N:9]=2)[CH:23]=[CH:22][N:21]=1)=[O:37]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 1118Sulfuric AcidHCID 31254N-MethylformamideHCID 6326419HCID 6326419, compound

Product 1

HCID 9808717HCID 9808717, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 62662Ferrous sulfate heptahydrateCatalyst

Conditions

Temperature
70 °C

Procedure

To a 3-necked flask charged with 1-(4-chloroanilino) 4-[(2-methyl-4-pyridyl)methyl] phthalazine (for preparation see Novartis patent WO98/35958, 11.02.98) (0.828 g, 2.39 mmol) in anhydrous N-methylformamide (4.8 mL) was added concentrated sulfuric acid)0.12 mL. 2.39 mmol) and iron (II) sulfate heptahydrate (0.33 g, 1.19 mmol). Hydrogen peroxide (0.256 mL, 8.35 mmol; 30 wt. % solution in water) was added dropwise to keep the internal temperature below 80° C. The resultant wine color reaction was then stirred at 70° C. for 5 h. The reaction mixture was cooled to RT and quenched with 10% aqueous sodium hydroxide (10 mL) followed by 10% aqueous ammonia (˜100 mL). The resultant brown precipitate was filtered through a pad of celite, and the filtrate was extracted with 10% methanol-dichloromethane (3×100 mL). The combined organic phases were washed with water (2×50 mL) and brine (1×50 mL), dried over MgSO4, filtered, and evaporated in vacuo. The crude oil was purified by flash column chromatography (10% acetone-dichloromethane followed by 1:4:20 v/v methanol-acetone-dichloromethane). Recrystallization from methanol afforded 0.165 g (0.404 mmol, 17% yield) of the title compound as a yellow solid. 1H-NMR (DMSO-d6) 9.28 (s, 1H), 8.70 (d, J=4.9, 1H), 8.58 (d, J=7.4, 1H), 8.49 (d, J=5.4, 1H), 8.12 (d, J=8.4, 1H), 7.89 to 7.99 (m, 5H), 7.51 (dd, J=5.1, 1.7, 1H), 7.38 (dd, J=7.1, 1.9, 2H), 4.67 (s, 2H), 2.75 (d, J=4.9, 3H); MS ES 404 (M+H)+, calc. 403; TLC (1:4:15 v/v methanol-acetone-dichloromethane) Rf=0.74.

Workup

  1. customthe internal temperature below 80° C
  2. customThe resultant wine color reaction
  3. temperatureThe reaction mixture was cooled to RT
  4. customquenched with 10% aqueous sodium hydroxide (10 mL)
  5. filtrationThe resultant brown precipitate was filtered through a pad of celite
  6. extractionthe filtrate was extracted with 10% methanol-dichloromethane (3×100 mL)
  7. washThe combined organic phases were washed with water (2×50 mL) and brine (1×50 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe crude oil was purified by flash column chromatography (10% acetone-dichloromethane followed by 1:4:20 v/v methanol-acetone-dichloromethane)
  12. customRecrystallization from methanol

Sources & evidence

ORD record
ord-744ecd847e2f4b1db7c7bc728702b56f
Source dataset
uspto-grants-2005_06
Patent number
US06903101B1

Reaction notes

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