Lapatinib Ditosylate → Lapatinib ditosylate anhydrous

HRID 2370677Notes

Reaction equation

HRID 2370677 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([OH:11])(=[O:10])=[O:9])=[CH:6][CH:7]=1.[CH3:12][C:13]1[CH:14]=[CH:15][C:16]([S:19]([OH:22])(=[O:21])=[O:20])=[CH:17][CH:18]=1.[CH3:23][S:24]([CH2:27][CH2:28][NH:29][CH2:30][C:31]1[O:35][C:34]([C:36]2[CH:37]=[CH:38][C:39]3[N:45]=[CH:44][N:43]=[C:42]([NH:46][C:47]4[CH:48]=[CH:49][C:50]([O:54][CH2:55][C:56]5[CH:57]=[CH:58][CH:59]=[C:60]([F:62])[CH:61]=5)=[C:51]([Cl:53])[CH:52]=4)[C:40]=3[CH:41]=2)=[CH:33][CH:32]=1)(=[O:26])=[O:25].O>CN(C=O)C>[S:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)([OH:11])(=[O:10])=[O:9].[S:19]([C:16]1[CH:17]=[CH:18][C:13]([CH3:12])=[CH:14][CH:15]=1)([OH:22])(=[O:21])=[O:20].[Cl:53][C:51]1[CH:52]=[C:47]([NH:46][C:42]2[C:40]3[C:39](=[CH:38][CH:37]=[C:36]([C:34]4[O:35][C:31]([CH2:30][NH:29][CH2:28][CH2:27][S:24]([CH3:23])(=[O:25])=[O:26])=[CH:32][CH:33]=4)[CH:41]=3)[N:45]=[CH:44][N:43]=2)[CH:48]=[CH:49][C:50]=1[O:54][CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[C:60]([F:62])[CH:61]=1

Participants

3

Reactant 1

HCID 11557040Lapatinib Ditosylate

Product 1

HCID 9941095Lapatinib ditosylate anhydrous

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Lapatinib ditosylate (3 g, 3.25 mmol, 99.3% HPLC purity was dissolved in DMF (18 mL) at 80° C. and stirred for 1 hour. The mixture was hot-filtered. MeCN (18 mL) was added into the filtrate at 80° C. The temperature was cooled to 70° C. and crystal precipitated. The mixture was kept at 70° C. for 1 h and then 60° C. for 1 h. The mixture was further cooled to 0° C. and stirred for 2 h. The crystals of lapatinib ditosylate were isolated by filtration and were dried at 40° C. under vacuum overnight. Lapatinib ditosylate (2.5 g, 2.70 mmol, 83% yield) with 99.9% HPLC purity was obtained. XRPD analysis indicated that this was Form 2 as disclosed in WO 2009/079541 A1.

Workup

  1. filtrationThe mixture was hot-filtered
  2. additionMeCN (18 mL) was added into the filtrate at 80° C
  3. customcrystal precipitated
  4. waitThe mixture was kept at 70° C. for 1 h
  5. wait60° C. for 1 h
  6. temperatureThe mixture was further cooled to 0° C.
  7. stirringstirred for 2 h

Sources & evidence

ORD record
ord-55f96a891d224866bdb9b36ab62cb35b
Source dataset
uspto-grants-2014_04
Patent number
US08710221B2

Reaction notes

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