Reaktion #89960

Reaktionsgleichung

tert-butyl 5-(2-(3-butyramidophenyl)-6-(2-chloroethoxy)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate

1-methylpiperazine

→

N-(3-(4-(1H-indazol-5-ylamino)-7-methoxy-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl) butyramide di-hydrochloride salt

Ausbeute 43.0%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to RT
2. 2
   SonstigeA precipitate formed which
3. 3
   Filtrationwas collected via filtration and it
4. 4
   Sonstigewas dried under vacuum
5. 5
   SonstigeThe precipitate was purified via preparative TLC (SiO2, CH2Cl2:MeOH:NH4OH 9:1:0.1)
6. 6
   SonstigeThe volatiles were removed in vacuo
7. 7
   Sonstigethe residue was triturated with Et2O
8. 8
   Filtrationfiltered
9. 9
   Sonstigedried under vacuum

Vorschrift

To a solution of tert-butyl 5-(2-(3-butyramidophenyl)-6-(2-chloroethoxy)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.170 g, 0.299 mmol) in DMSO (2 mL) was added 1-methylpiperazine (0.5 mL). The subsequent mixture was heated at 85° C. for 2.5 h upon which it was allowed to cool to RT and poured into ice-water (100 mL). A precipitate formed which was collected via filtration and it was dried under vacuum. The precipitate was purified via preparative TLC (SiO2, CH2Cl2:MeOH:NH4OH 9:1:0.1). The purified compound was taken up in CH2Cl2 (2 mL) and HCl (4M in 1,4 dioxane, 10 mL) and stirred at RT for 4 h. The volatiles were removed in vacuo and the residue was triturated with Et2O, filtered and dried under vacuum to give N-(3-(4-(1H-indazol-5-ylamino)-7-methoxy-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl) butyramide di-hydrochloride salt (0.085 g, 0.128 mmol, 43% over two steps). MS 595 (M+1). HPLC retention time 4.337 mins.

Quelle