Reaktion #166247

Reaktionsgleichung

4-(2-fluoro-4-methylsulfanyl-phenylamino)-1H-indazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide

hydrochloric acid

→

solid

Ausbeute 55.0%

4-(2-Fluoro-4-methylsulfanyl-phenylamino)-1H-indazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide

Ausbeute 55.0%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was then concentrated in vacuo
2. 2
   workup.DISSOLUTIONthe residue dissolved in methanol and to this solution
3. 3
   workup.ADDITIONwas added water causing a precipitate
4. 4
   Sonstigeto form which
5. 5
   Filtrationwas filtered off
6. 6
   ExtraktionThe filtrate was extracted twice with ethyl acetate
7. 7
   Trocknenthe combined extracts dried (Na2SO4)
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated in vacuo
10. 10
    Sonstigeto give a solid
11. 11
    SonstigeThe solid was triturated in diethyl ether

Vorschrift

A solution of 4-(2-fluoro-4-methylsulfanyl-phenylamino)-1H-indazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide (45 mg, 0.112 mmol) in methanol (5 mL) was treated with hydrochloric acid (1M, 0.225 mL, 0.22 mmol) and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was then concentrated in vacuo and the residue dissolved in methanol and to this solution was added water causing a precipitate to form which was filtered off. The filtrate was extracted twice with ethyl acetate, the combined extracts dried (Na2SO4), filtered and concentrated in vacuo. The crude product was combined with the earlier solid precipitate and subjected to flash chromatography (Si—PPC, gradient 0 to 10% methanol in DCM) to give a solid. The solid was triturated in diethyl ether to give a pale tan solid (23 mg, 55%). LCMS (Method A) RT 7.79 [M+H]+ 377. 1H NMR (MeOD, 400 MHz): 7.52-7.44 (1 H, m), 7.21-7.09 (3 H, m), 7.06 (1 H, dd, J=8.41, 2.08 Hz), 6.93 (1 H, d, J=8.88 Hz), 4.54 (1 H, s), 4.02-3.98 (2 H, m), 3.75 (2 H, dd, J=5.28, 4.05 Hz), 2.48 (3 H, s).

Quelle