Boron tribromide → Vatalanib metabolite M26

HRID 1384150Notes

Reaction equation

HRID 1384150 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 dichioromethane 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(Grads5-40)=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-0396c00ac99b4d4f80b577a99a3e052b
Source dataset
uspto-grants-2001_07
Patent number
US06258812B1

Reaction notes

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