تفاعل #48120

معادلة التفاعل

4-Fluorobenzenesulfonyl chloride

Sodium hydride

(4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

intermediate 1

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

→

desired product

المردود 60.1%

(4,4-Difluoro-piperidin-1-yl)-[1-(4-fluoro-benzenesulfonyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

المردود 60.1%

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction mixture was stirred at 70° C. overnight
2. 2
   أخرىThe reaction mixture was partitioned between ethyl acetate and water
3. 3
   استخلاصThe aqueous layer was extracted with ethyl acetate
4. 4
   غسيلthe combined organic fractions were washed with water and brine
5. 5
   تجفيفdried over sodium sulfate
6. 6
   ترشيحfiltered
7. 7
   أخرىevaporated to dryness
8. 8
   أخرىpurified on silica gel
9. 9
   غسيلeluting with dichloromethane/methanol 49:1

الإجراء التجريبي

Sodium hydride (60% dispersion in oil, 24 mg, 1.1 eq.) was added to a mixture of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 200 mg, 1.0 eq.) in N,N-dimethylformamide (2 mL) and stirred at 70° C. for 30 min. 4-Fluorobenzenesulfonyl chloride (115 mg, 1.2 eq.) was added and the reaction mixture was stirred at 70° C. overnight. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with dichloromethane/methanol 49:1 to yield 167 mg (60%) of the desired product as yellow foam. MS (m/e): 564.4 (MH+, 100%).

المصدر