Potassium Carbonate → 4-[4-bromo-3-(methyloxy)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one
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])=[CH:4][C:3]=1[O:26][CH3:27].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])=[CH:4][C:3]=1[O:26][CH3:27]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 115 °C
Procedure
N-[4-bromo-3-(methyloxy)phenyl]-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide (500 mg, 0.911 mmol) and potassium carbonate (445 mg, 3.22 mmol) were added to a round-bottom flask and suspended in water (50 mL). The mixture was refluxed overnight at 115° C. Analysis by LCMS indicated formation of desired product (and other major by-products). A white solid (that was not desired product) had collected at the bottom of the flask and was filtered off. The pH of the filtrate was adjusted to ˜6 with 1N aq HCl and was partitioned with ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to an oil. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, then 0-30% isopropanol/ethyl acetate). The desired fractions were combined and concentrated in vacuo to afford the title product as an off-white solid (151 mg, 38%). MS(ES)+ m/e 421.0, 422.9 M+H]+.
Sources & evidence
- ORD record
- ord-d8eb95710cc94edaa19314aeaa9a1f11
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340529B2
Reaction notes
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