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

HRID 2405343Notes

Reaction equation

HRID 2405343 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][NH:12][C:13](=O)[CH2:14][C@@H:15]2[CH2:19][CH2:18][N:17]([C:20]([CH:22]3[CH2:24][CH2:23]3)=[O:21])[CH2:16]2)=[O:10])=[C:4]([CH3:26])[CH:3]=1.C([O-])([O-])=O.[K+].[K+]>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][N:17]([C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[CH2:16]3)=[N:12][NH:11][C:9]2=[O:10])=[C:4]([CH3:26])[CH:3]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 71087270N-(4-Bromo-2-methylphenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide

Product 1

HCID 710875134-(4-bromo-2-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 54.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

To a suspension of N-(4-bromo-2-methylphenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide (925 mg, 2.185 mmol) in water (45 mL) was added K2CO3 (1510 mg, 10.93 mmol). The reaction flask was equipped with a reflux condenser and heated to reflux (bath=130° C.) with stirring. After 5 h (LCMS indicated no starting material remained), the reaction mixture was cooled to room temperature and filtered to collect a small amount of white precipitate (this was determined to contain very little product so it was discarded). The aqueous filtrate was adjusted to pH˜5.5 with 1N aq HCl and extracted with three 100 mL portions of ethyl acetate. The combined organics were dried over Na2SO4, filtered, concentrated under reduced pressure and dried to constant weight under high vacuum to provide 4-(4-bromo-2-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (485 mg, 1.197 mmol, 54.8% yield) as a white solid. MS(ES)+ m/e 405.2, 407.4 [M+H]+. The product was determined to be 90% pure by LCMS (UV214) and was carried on in the next step without further purification.

Workup

  1. customThe reaction flask was equipped with a reflux condenser
  2. temperatureheated
  3. temperaturewas cooled to room temperature
  4. filtrationfiltered
  5. customto collect a small amount of white precipitate (
  6. extractionextracted with three 100 mL portions of ethyl acetate
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customdried to constant weight under high vacuum

Sources & evidence

ORD record
ord-29d47b7d827e43e1a9f6a6d2afc98813
Source dataset
uspto-grants-2014_08
Patent number
US08802864B2

Reaction notes

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