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

Reaktionsgleichung

Reaktionsgleichung von HRID 525150
[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

Komponenten

5

Edukt 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

Produkt 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-oneAusbeute 63,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-716b24eeb6db4088b9f796946347775c
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340529B2

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