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

HRID 525168Notes

Reaction equation

HRID 525168 reaction equation
Cl.[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C:21]([CH2:22][C@@H:23]5[CH2:27][CH2:26][NH:25][CH2:24]5)=[N:20][NH:19][C:18]4=[O:28])=[CH:13][CH:12]=3)=[CH:10][C:5]=2[CH:4]=[CH:3]1.C(N(CC)C(C)C)(C)C.[C:38](Cl)(=[O:41])[CH2:39][CH3:40]>ClCCl>[O:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C:21]([CH2:22][C@@H:23]5[CH2:27][CH2:26][N:25]([C:38](=[O:41])[CH2:39][CH3:40])[CH2:24]5)=[N:20][NH:19][C:18]4=[O:28])=[CH:13][CH:12]=3)=[CH:10][C:5]=2[CH:4]=[CH:3]1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 673758814-[4-(1-benzofuran-5-yl)phenyl]-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride

Product 1

HCID 673540964-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-propanoyl-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under nitrogen, a mixture of 4-[4-(1-benzofuran-5-yl)phenyl]-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (116 mg, 0.292 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.88 mmol) in dichloromethane (1.3 mL) was stirred at room temperature for 2 min. The mixture was cooled to 0° C. and treated with propionyl chloride (0.026 mL, 0.292 mmol) dropwise by syringe. The mixture became a dark brown solution and the reaction was stirred at 0° C. for 90 min. The reaction was quenched with water (2 mL) and diluted with ethyl acetate (20 mL). The mixture was transferred to a reparatory funnel, water (10 mL) was added and the layers were separated. The pH of the aqueous layer was tested by pH paper and found to be pH˜5-6. The aqueous layer was extracted with ethyl acetate (10 mL). The organic layers were combined, dried over magnesium sulfate and concentrated in vacuo to give a tan foamy solid. Purification of the residue by silica gel chromatography (Analogix IF280, SF10-4-g, 0-10% MeOH/EtOAc, 30 min) provided the title product as an ivory solid (74 mg, 61%). MS(ES)+ m/e 417.2 [M+H]+.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringthe reaction was stirred at 0° C. for 90 min
  3. customThe reaction was quenched with water (2 mL)
  4. additiondiluted with ethyl acetate (20 mL)
  5. customThe mixture was transferred to a reparatory funnel
  6. additionwater (10 mL) was added
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted with ethyl acetate (10 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customto give a tan foamy solid
  12. customPurification of the residue by silica gel chromatography (Analogix IF280, SF10-4-g, 0-10% MeOH/EtOAc, 30 min)

Sources & evidence

ORD record
ord-1fc1fe86dd144ea6a97f7a42c5b18d5f
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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