反応 #166247

反応方程式

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

hydrochloric acid

→

solid

収率 55.0%

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

収率 55.0%

溶媒

methanol

反応条件

後処理

1. 1
   濃縮The 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
   その他to form which
5. 5
   ろ過was filtered off
6. 6
   抽出The filtrate was extracted twice with ethyl acetate
7. 7
   乾燥the combined extracts dried (Na2SO4)
8. 8
   ろ過filtered
9. 9
   濃縮concentrated in vacuo
10. 10
    その他to give a solid
11. 11
    その他The solid was triturated in diethyl ether

実験手順

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).

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