Phthalimide → 2-(2-aminoethyl)-4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525150

반응식

HRID 525150 반응식
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[C:20](=[O:21])[N:19]([CH2:22][CH2:23][N:24]5C(=O)C6C(=CC=CC=6)C5=O)[N:18]=[C:17]4[CH2:35][C@@H:36]4[CH2:40][CH2:39][N:38]([C:41]([CH:43]5[CH2:45][CH2:44]5)=[O:42])[CH2:37]4)=[CH:12][CH:11]=3)=[CH:9][C:4]=2[CH:3]=[CH:2]1.O.NN.C1(=O)NC(=O)C2=CC=CC=C12>C(O)C>[NH2:24][CH2:23][CH2:22][N:19]1[C:20](=[O:21])[N:16]([C:13]2[CH:14]=[CH:15][C:10]([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH:2]=[CH:3][C:4]=4[CH:9]=3)=[CH:11][CH:12]=2)[C:17]([CH2:35][C@@H:36]2[CH2:40][CH2:39][N:38]([C:41]([CH:43]3[CH2:45][CH2:44]3)=[O:42])[CH2:37]2)=[N:18]1

참가 물질

5

반응물 3

HCID 6809PhthalimideHCID 24654Hydrazine hydrate (1:1)HCID 673759832-[2-(4-[4-(1-benzofuran-5-yl)phenyl]-3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)ethyl]-1H-isoindole-1,3(2H)-dione

생성물 1

HCID 533715722-(2-aminoethyl)-4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one수율 63.8%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
60 °C

실험 절차

To a 50 mL round bottom flask containing 2-[2-(4-[4-(1-benzofuran-5-yl)phenyl]-3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)ethyl]-1H-isoindole-1,3(2H)-dione (130 mg, 0.216 mmol) and ethanol (4 mL) was added hydrazine monohydrate (82 mg, 2.55 mmol, 11 eq). The flask was equipped with a condenser and the reaction was stirred at 60° C. for 1 h. Analysis by LC/MS displayed the phthalimide deprotection was complete. The reaction was cooled to room temperature and concentrated in vacuo. The residue was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 10-45% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (65 mg, 63%). MS(ES)+ m/e 472.2 [M+H]+.

후처리

  1. customThe flask was equipped with a condenser
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 10-45% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  5. additionThe product fractions were neutralized with the addition of saturated aq sodium bicarbonate
  6. extractionextracted with dichloromethane
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-716b24eeb6db4088b9f796946347775c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340529B2

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