Hydrochloric Acid → Vatalanib dihydrochloride

HRID 49883Notes

Reaction equation

HRID 49883 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][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]=[CH:20][CH:19]=3)=[N:9][N:8]=2)=[CH:4][CH:3]=1.[ClH:26].CCOCC>CO>[ClH:1].[ClH:26].[Cl:1][C:2]1[CH:3]=[CH:4][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]=[CH:20][CH:19]=3)=[N:9][N:8]=2)=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 151194Vatalanib

Product 1

HCID 22386467Vatalanib dihydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

While stirring, 6.24 g (18 mmol) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine is dissolved in 180 ml methanol at about 50° C. The solution is cooled to RT and mixed slowly with 3.15 ml (38.2 mmol) conc. (about 37%) hydrochloric acid. When 100 ml ether is added dropwise to the reaction mixture, a crystalline precipitate forms. The suspension thereof is stirred for 15 min at RT. A further 80 ml is added dropwise to the suspension, which is stirred for a further 15 min at 20° C. and then for 0.5 h under ice cooling. After filtration, washing of the filter residue with ether, drying under HV (5 h, 90° C.) and equilibration (room atmosphere, 24 h, 20° C.), title compound is obtained with a water content of 8.63%; m.p. 268-270° C.; 1H NMR (DMSO-d6): Identical to Example 1 apart from high-field shift of signals by 0.03 ppm.

Workup

  1. stirringThe suspension thereof is stirred for 15 min at RT
  2. additionA further 80 ml is added dropwise to the suspension, which
  3. stirringis stirred for a further 15 min at 20° C.
  4. filtrationAfter filtration
  5. washwashing of the filter residue with ether
  6. customdrying under HV (5 h, 90° C.) and equilibration (room atmosphere, 24 h, 20° C.)

Sources & evidence

ORD record
ord-98734e6aed2f4ea49b490eb0b0a31ad9
Source dataset
uspto-grants-2004_03
Patent number
US06710047B2

Reaction notes

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