反応 #1131903

反応方程式

Lapatinib ditosylate

→

lapatinib ditosylate

N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-((2-(methylsulfonyl)ethylamino)methyl)furan-2-yl)quinazolin-4-amine ditosylate

溶媒

DMF

反応条件

後処理

1. 1
   ろ過The mixture was hot-filtered
2. 2
   workup.ADDITIONMeCN (18 mL) was added into the filtrate at 80° C
3. 3
   その他crystal precipitated
4. 4
   workup.WAITThe mixture was kept at 70° C. for 1 h
5. 5
   workup.WAIT60° C. for 1 h
6. 6
   温度The mixture was further cooled to 0° C.
7. 7
   workup.STIRRINGstirred for 2 h

実験手順

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 (FIG. 9) indicated that this was Form 2 as disclosed in WO 2009/079541 A1.

出典