تفاعل #164766

معادلة التفاعل

N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

NaOH

5-methoxypyrazine-2-carboxylic acid

1-Hydroxybenzotriazole

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

title compound

المردود 92.4%

N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-methoxy-pyrazine-2-carboxamide

المردود 92.4%

المذيبات

dichloromethane

dimethylformamide

water

ظروف التفاعل

المعالجة

1. 1
   استخلاصThe mixture is extracted with ethyl acetate (3×)
2. 2
   تجفيفThe combined organic extracts are dried over sodium sulfate
3. 3
   ترشيحfiltered
4. 4
   أخرىthe solvent removed in vacuo
5. 5
   أخرىThe crude product is purified over silica gel with a 20 minute 5% to 100% ethyl acetate in hexanes gradient

الإجراء التجريبي

N-[(4aR,7aS)-7a-(3-Aminophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (400 mg, 891.81 μmole) and 5-methoxypyrazine-2-carboxylic acid (165 mg, 1.07 mmol) are combined in dichloromethane (4 mL) and dimethylformamide (0.5 mL). 1-Hydroxybenzotriazole (160 mg, 1.16 mmol) and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (226 mg, 1.16 mmol) are added and the resulting mixture is stirred for 5 hours at room temperature under nitrogen. The reaction mixture is diluted with water and the pH is adjusted to ˜12 with 1 N NaOH. The mixture is extracted with ethyl acetate (3×). The combined organic extracts are dried over sodium sulfate, filtered and the solvent removed in vacuo. The crude product is purified over silica gel with a 20 minute 5% to 100% ethyl acetate in hexanes gradient to give the title compound (482 mg, 92%). ES/MS (m/e): 585 (M+H).

المصدر