Boron tribromide → Vatalanib metabolite M26

HRID 49908Notes

Reaction equation

HRID 49908 reaction equation
B(Br)(Br)Br.[Cl:5][C:6]1[CH:29]=[CH:28][C:9]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)=[N:13][N:12]=2)=[CH:8][C:7]=1[O:30]C>ClCCl>[Cl:5][C:6]1[CH:29]=[CH:28][C:9]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)=[N:13][N:12]=2)=[CH:8][C:7]=1[OH:30]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 6419393HCID 6419393, compound

Product 1

HCID 22741987Vatalanib metabolite M26

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2 ml boron tribromide (≈1M in CH2Cl2) is mixed with a suspension of 0.19 g (0.50 mmol) 1-(4-chloro-3-methoxyanilino)-4-(4-pyridylmethyl)phthalazine (Example 68B) in 4 ml dichloromethane at 0° C. under a nitrogen atmosphere. The resinous mixture is left to stand for 18 h at RT, the dichloromethane phase is then decanted, and the glutinous residue stirred with 10 ml THF and 5 ml sat. NaHCO3 solution. The resulting suspension is filtered, the filter residue washed with THF and discarded. The THF phase is separated and dried (Na2SO4), concentrated by evaporation, chromatographed (SiO2; acetate/CH3OH, 40:1→19:1) and title compound crystallized from acetonitrile/methanol: m.p.: 245-246° C.; HPLC: tRet(Grad5-40)=8.8; FAB MS (M+H)+=363.

Workup

  1. waitThe resinous mixture is left
  2. customthe dichloromethane phase is then decanted
  3. filtrationThe resulting suspension is filtered
  4. washthe filter residue washed with THF
  5. customThe THF phase is separated
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated by evaporation
  8. customchromatographed (SiO2; acetate/CH3OH, 40:1→19:1) and title compound
  9. customcrystallized from acetonitrile/methanol

Sources & evidence

ORD record
ord-752133b08fb24a7295af5f5b55e78ce9
Source dataset
uspto-grants-2004_03
Patent number
US06710047B2

Reaction notes

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