تفاعل #53717

معادلة التفاعل

N-tert-butoxycarbonylindole-2-boronic acid

sodium hydrogencarbonate

tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-trifluoromethoxybenzenesulfonylamino)indazolecarboxylate

→

N-[3-(1H-indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxy-benzenesulfonamide

المردود 58.3%

المذيبات

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAfter cooling to a temperature in the region of 20° C.
2. 2
   ترشيحthe catalyst is filtered through sintered glass with Celite® 535
3. 3
   تركيزthe filtrate is concentrated to dryness under reduced pressure in a rotary evaporator
4. 4
   أخرىThe reaction crude
5. 5
   أخرىis purified by preparative HPLC chromatography
6. 6
   workup.ADDITIONThe fractions containing the expected product
7. 7
   تركيزconcentrated
8. 8
   غسيلwashed with 10 ml of a saturated sodium hydrogencarbonate solution
9. 9
   تجفيفThe organic phase is dried over magnesium sulfate
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated to dryness under reduced pressure

الإجراء التجريبي

N-[3-(1H-Indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxybenzenesulfonamide can be obtained in the following way: 213.3 mg N-tert-butoxycarbonylindole-2-boronic acid in dimer form and 243 μl of a saturated sodium hydrogencarbonate solution and then 63.4 mg of tetrakis(triphenylphosphine)palladium[0] are added to a solution of 150 mg of tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-trifluoromethoxybenzenesulfonylamino)indazolecarboxylate in 4.5 ml of dimethylformamide. The suspension is heated in the region of 120° C. for 18 hours. After cooling to a temperature in the region of 20° C., the catalyst is filtered through sintered glass with Celite® 535, and the filtrate is concentrated to dryness under reduced pressure in a rotary evaporator. The reaction crude is purified by preparative HPLC chromatography coupled to a mass detector (LC/MS, conditions A). The fractions containing the expected product are pooled and concentrated, and then the base is released from the trifluoroacetate salt by being taken up in 10 ml of dichloromethane and washed with 10 ml of a saturated sodium hydrogencarbonate solution. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. 60.5 mg of N-[3-(1H-indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxy-benzenesulfonamide are thus obtained in the form of a white solid melting at 172-174° C. (analytical LC/MS analysis: Tr=3.73 minutes; [M+H]+=473.07).

المصدر