Propionyl chloride → 4-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-propanoyl-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2405434Notes

Reaction equation

HRID 2405434 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][NH:17][CH2:16]3)=[N:12][NH:11][C:10]2=[O:20])=[C:5]([F:21])[CH:4]=1.C(N(CC)C(C)C)(C)C.[C:31](Cl)(=[O:34])[CH2:32][CH3:33]>ClCCl>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][N:17]([C:31](=[O:34])[CH2:32][CH3:33])[CH2:16]3)=[N:12][NH:11][C:10]2=[O:20])=[C:5]([F:21])[CH:4]=1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 673755214-(4-bromo-2-fluorophenyl)-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride

Product 1

HCID 673544204-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-propanoyl-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 4 mL screwcap vial was placed 4-(4-bromo-2-fluorophenyl)-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (0.318 mmol). Added to the vial in succession was dichloromethane (3 mL), N,N-diisopropylethylamine (0.916 mmol), and propanoyl chloride (0.319 mmol). The vial was capped and stirred at room temperature overnight. The solution was concentrated in vacuo and the residue was purified by reverse phase HPLC (10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA). The combined product fractions were concentrated in vacuo for 1 h to remove the acetonitrile. The aqueous solution was neutralized with the addition of saturated aqueous sodium bicarbonate, and extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (100 mg, 79% yield). MS(ES)+ m/e 397.0, 399.1 [M+H]+.

Workup

  1. additionAdded to the vial in succession
  2. customThe vial was capped
  3. concentrationThe solution was concentrated in vacuo
  4. customthe residue was purified by reverse phase HPLC (10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  5. concentrationThe combined product fractions were concentrated in vacuo for 1 h
  6. customto remove the acetonitrile
  7. additionThe aqueous solution was neutralized with the addition of saturated aqueous sodium bicarbonate
  8. extractionextracted twice with dichloromethane
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-586e74364b414b81b9b172de46860217
Source dataset
uspto-grants-2014_08
Patent number
US08802864B2

Reaction notes

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