Réaction #166247

Équation de réaction

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

hydrochloric acid

→

solid

Rendement 55.0%

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

Rendement 55.0%

Solvants

methanol

Conditions de réaction

Traitement

1. 1
   ConcentrationThe 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
   Autreto form which
5. 5
   Filtrationwas filtered off
6. 6
   ExtractionThe filtrate was extracted twice with ethyl acetate
7. 7
   Séchagethe combined extracts dried (Na2SO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo
10. 10
    Autreto give a solid
11. 11
    AutreThe solid was triturated in diethyl ether

Mode opératoire

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).

Source