تفاعل #4091

معادلة التفاعل

maleic acid

1-(4-bromo-2-aminophenyl)indoline

potassium carbonate

4-methyl-1-piperazinecarbonyl chloride hydrochloride

potassium carbonate

carbonyl chloride

→

N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide maleate

المردود 39.8%

المذيبات

ethanol

chloroform

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction was refluxed for 6 hours when
2. 2
   workup.ADDITIONwas added
3. 3
   درجة الحرارةAfter refluxing overnight (about 16 hours)
4. 4
   درجة الحرارةthe reaction was cooled
5. 5
   أخرىThe layers were separated
6. 6
   غسيلthe organic phase was washed thrice with water
7. 7
   تجفيفdried over Na2SO4
8. 8
   تركيزconcentrated in vacuo
9. 9
   workup.DISSOLUTIONThe residue was dissolved in 200 ml of toluene
10. 10
    workup.ADDITIONcontaining 1.5 kg of silica gel
11. 11
    غسيلElution first with toluene
12. 12
    workup.DISSOLUTIONThis was dissolved in 100 ml of ethanol
13. 13
    أخرىThe maleate salt was collected
14. 14
    أخرىdried
15. 15
    أخرىRecrystallization from methanol (charcoal)

الإجراء التجريبي

To a stirred solution, under nitrogen of 43.5 g (0.15 mole) of 1-(4-bromo-2-aminophenyl)indoline of Example 3b and 82.8 g (0.60 mole) of milled potassium carbonate in 1000 ml of chloroform was added 44.7 g (0.225 mole) of 4-methyl-1-piperazinecarbonyl chloride hydrochloride in portions over 10 minutes. The reaction was refluxed for 6 hours when an additional charge of 10.4 g (0.075 mole) of potassium carbonate and 14.9 g (0.075 mole) of the carbonyl chloride reagent was added. After refluxing overnight (about 16 hours), the reaction was cooled, treated with 500 ml of water, and stirred vigorously for 15 minutes. The layers were separated and the organic phase was washed thrice with water, dried over Na2SO4, and concentrated in vacuo. The residue was dissolved in 200 ml of toluene and adsorbed on a tall chromatography column containing 1.5 kg of silica gel packed in toluene. Elution first with toluene, then with increasing percentages of dichloromethane in toluene, (25% per step), followed by dichloromethane alone, and finally with 1% methanol in dichloromethane brought forth 24 g (overall 39% yield) of fairly pure urea. This was dissolved in 100 ml of ethanol and treated with a solution of 6.96 g (0.06 mole) of maleic acid dissolved in 50 ml of ethanol. The maleate salt was collected, dried, and found to weigh 17.3 g (22% overall), m.p. 175°-177° C. dec. Recrystallization from methanol (charcoal) afforded 12.7 g (16% overall yield) of N-[5-bromo-2-(2,3-dihydro-1H-indol-1-yl)phenyl]-4-methyl-1-piperazinecarboxamide maleate, m.p. 175°-177° C. dec.

المصدر