Lapatinib → p-Toluenesulfonic acid

HRID 1044716Notes

Reaction equation

HRID 1044716 reaction equation
[CH3:1][S:2]([CH2:5][CH2:6][NH:7][CH2:8][C:9]1[O:13][C:12]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]4[CH:26]=[CH:27][C:28]([O:32][CH2:33][C:34]5[CH:35]=[CH:36][CH:37]=[C:38]([F:40])[CH:39]=5)=[C:29]([Cl:31])[CH:30]=4)[C:18]=3[CH:19]=2)=[CH:11][CH:10]=1)(=[O:4])=[O:3].[CH3:41][C:42]1[CH:43]=[CH:44][C:45]([S:48]([OH:51])(=[O:50])=[O:49])=[CH:46][CH:47]=1.[CH3:52][C:53]1[CH:54]=[CH:55][C:56]([S:59]([OH:62])(=[O:61])=[O:60])=[CH:57][CH:58]=1.CS(CCNCC1OC(C2C=CC3N=CN=C(NC4C=CC(OCC5C=CC=C(F)C=5)=C(Cl)C=4)C=3C=2)=CC=1)(=O)=[O:65].O>>[CH3:41][C:42]1[CH:47]=[CH:46][C:45]([S:48]([OH:51])(=[O:50])=[O:49])=[CH:44][CH:43]=1.[CH3:52][C:53]1[CH:58]=[CH:57][C:56]([S:59]([OH:62])(=[O:61])=[O:60])=[CH:55][CH:54]=1.[CH3:1][S:2]([CH2:5][CH2:6][NH:7][CH2:8][C:9]1[O:13][C:12]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]4[CH:26]=[CH:27][C:28]([O:32][CH2:33][C:34]5[CH:35]=[CH:36][CH:37]=[C:38]([F:40])[CH:39]=5)=[C:29]([Cl:31])[CH:30]=4)[C:18]=3[CH:19]=2)=[CH:11][CH:10]=1)(=[O:4])=[O:3].[OH2:65].[C:42]1([CH3:41])[CH:43]=[CH:44][C:45]([S:48]([OH:51])(=[O:49])=[O:50])=[CH:46][CH:47]=1

Participants

4

Reactant 2

HCID 208908Lapatinib2×HCID 11557040Lapatinib Ditosylate2×

Product 2

HCID 6101p-Toluenesulfonic acidHCID 11557040Lapatinib Ditosylate

Procedure

Lapatinib prepared using the method of this embodiment can be isolated, or more preferably it can be directly converted into highly pure lapatinib ditosylate salt without isolation of the lapatinib from the step iii) reaction product mixture. The isolated lapatinib ditosylate has a HPLC purity of 97.0-99.9%, preferably >99.0%, most preferably >99.8%. The reaction product mixture from the step iii) is quenched with a basic aqueous solution such as aq. NaOH, separated and the organic phase is washed with an acidic aqueous solution such as aq. NH4Cl. The organic phase is then filtered and lapatinib ditosylate as crystalline Form I is obtained by crystallisation from the organic phase in the presence of p-toluenesulfonic acid. The lapatinib ditosylate is isolated by filtration or centrifugation, or other methods of solid isolation.

Workup

  1. customcan be isolated
  2. customreaction product mixture
  3. customThe reaction product mixture from the step iii) is quenched with a basic aqueous solution such as aq. NaOH
  4. customseparated
  5. washthe organic phase is washed with an acidic aqueous solution such as aq. NH4Cl
  6. filtrationThe organic phase is then filtered

Sources & evidence

ORD record
ord-c138e68d3cc54adc8415e7322c24cc61
Source dataset
uspto-grants-2013_10
Patent number
US08563719B2

Reaction notes

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