تفاعل #166247

معادلة التفاعل

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

hydrochloric acid

→

solid

المردود 55.0%

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

المردود 55.0%

المذيبات

methanol

ظروف التفاعل

المعالجة

1. 1
   تركيزThe 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
   أخرىto form which
5. 5
   ترشيحwas filtered off
6. 6
   استخلاصThe filtrate was extracted twice with ethyl acetate
7. 7
   تجفيفthe combined extracts dried (Na2SO4)
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated in vacuo
10. 10
    أخرىto give a solid
11. 11
    أخرىThe solid was triturated in diethyl ether

الإجراء التجريبي

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).

المصدر