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

Reaction equation

HRID 525150 reaction equation
[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

Participants

5

Reactant 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

Product 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-oneYield 63.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-716b24eeb6db4088b9f796946347775c
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Linked notes

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