Reacción #166247

Ecuación de reacción

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

hydrochloric acid

→

solid

Rendimiento 55.0%

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

Rendimiento 55.0%

Disolventes

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe 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
   Otroto form which
5. 5
   Filtraciónwas filtered off
6. 6
   ExtracciónThe filtrate was extracted twice with ethyl acetate
7. 7
   Secadothe combined extracts dried (Na2SO4)
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated in vacuo
10. 10
    Otroto give a solid
11. 11
    OtroThe solid was triturated in diethyl ether

Procedimiento

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).

Fuente