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

HRID 525194Notes

Reaction equation

HRID 525194 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]([Cl: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]([Cl:26])[CH:3]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 71087424N-(4-bromo-2-chlorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide

Product 1

HCID 673771034-(4-bromo-2-chlorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 46%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of N-(4-bromo-2-chlorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide (1.3 g, 2.93 mmol) in water (60 mL) was added K2CO3 (2.025 g, 14.65 mmol). The reaction flask was equipped with a reflux condenser and heated to reflux (bath=120° C.) with stirring. After 5 h (analysis by 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 and was discarded). The aqueous filtrate was adjusted to pH˜5.5 with 1N aq HCl and extracted with ethyl acetate (2×). The combined organics were dried over Na2SO4, filtered, and evaporated to provide the title product (570 mg, 1.339 mmol, 46% yield) as a foam. The product was determined to be 75% pure by LCMS (UV214) and was carried on in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 7.80 (dt, J=2.3, 5.7 Hz, 1H), 7.68-7.52 (m, 1H), 7.28-7.22 (m, 1H), 4.01-3.35 (m, 2H), 3.34-2.99 (m, 1H), 2.74-2.08 (m, 3H), 1.82-1.66 (m, 1H), 1.59-1.51 (m, 1H), 1.12-0.91 (m, 1H), 0.83-0.69 (m, 1H).

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 ethyl acetate (2×)
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-dd1dcafeaa204c4aa93ee50ef086ef65
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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