Potassium Carbonate → 4-(4-bromo-2,6-difluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525171Notes

Reaction equation

HRID 525171 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9][C:10]([NH:12][NH:13][C:14](=O)[CH2:15][C@@H:16]2[CH2:20][CH2:19][N:18]([C:21]([CH:23]3[CH2:25][CH2:24]3)=[O:22])[CH2:17]2)=[O:11])=[C:4]([F:27])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+]>O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14]([CH2:15][C@@H:16]3[CH2:20][CH2:19][N:18]([C:21]([CH:23]4[CH2:25][CH2:24]4)=[O:22])[CH2:17]3)=[N:13][NH:12][C:10]2=[O:11])=[C:4]([F:27])[CH:3]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 71087576N-(4-bromo-2,6-difluorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide

Product 1

HCID 710872394-(4-bromo-2,6-difluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 13.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

To a round bottom flask, N-(4-bromo-2,6-difluorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide (2860 mg, 6.42 mmol) and potassium carbonate (4000 mg, 28.9 mmol) were added and suspended in water (200 mL). The mixture was refluxed for 16 h at 115° C. Analysis by LCMS indicated consumption of starting material and formation of desired product and by-products related to the starting material. The solution was neutralized to pH=7 with 1N aq HCl and 150 mL of ethyl acetate was added. The aqueous phase was extracted with ethyl acetate (3×) and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-20% isopropanol/ethyl acetate) provided the title product as a white solid (360 mg, 13%). MS(ES)+ m/e 426.9, 428.6 [M+H]+.

Workup

  1. customconsumption of starting material and formation of desired product and by-products
  2. additionwas added
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by silica gel chromatography (0-20% isopropanol/ethyl acetate)

Sources & evidence

ORD record
ord-a065457ada7b4520abc838b99db9d259
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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