Acetonitrile → Lapatinib ditosylate anhydrous

HRID 1044720Notes

Reaction equation

HRID 1044720 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.CC#N>CS(C)=O>[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

4

Reactant 2

HCID 6342Acetonitrile2×HCID 11557040Lapatinib Ditosylate

Product 1

HCID 9941095Lapatinib ditosylate anhydrous

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Lapatinib ditosylate (5.0 g, 5.4 mmol, 96.5% HPLC purity with the maximum individual impurity at 0.8%) was dissolved in DMSO (10 mL) at 70° C. (internal temperature). MeCN (10 mL) was added dropwise into the mixture at 70-80° C. (internal temperature) and was stirred at this temperature for 1 h. Over a 4 h period the mixture was cooled to room temperature. MeCN (30 mL) was added dropwise, and the mixture was stirred for 1 h, then filtered and washed with MeCN (10 mL). The filter cake was dried under vacuum at 60° C. for 16 h to give 4.0 g lapatinib ditosylate as crystalline Form 1 (as disclosed in U.S. Pat. No. 7,157,466 B2) with 99.6% HPLC purity in 78% HPLC yield.

Workup

  1. stirringthe mixture was stirred for 1 h
  2. filtrationfiltered
  3. washwashed with MeCN (10 mL)
  4. customThe filter cake was dried under vacuum at 60° C. for 16 h

Sources & evidence

ORD record
ord-d40eda1677a840ff93b83c7033a51786
Source dataset
uspto-grants-2013_10
Patent number
US08563719B2

Reaction notes

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