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

HRID 525162Notes

Reaction equation

HRID 525162 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[C:4]([CH3:25])[CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[CH:36][C:37]3[O:41][CH:40]=[CH:39][C:38]=3[CH:42]=2)O1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[O:41]1[C:37]2[CH:36]=[CH:35][C:34]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[C:12]([CH2:13][C@@H:14]5[CH2:18][CH2:17][N:16]([C:19]([CH:21]6[CH2:23][CH2:22]6)=[O:20])[CH2:15]5)=[N:11][NH:10][C:9]4=[O:24])=[C:4]([CH3:25])[CH:3]=3)=[CH:42][C:38]=2[CH:39]=[CH:40]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27951905-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuranHCID 710875134-(4-bromo-2-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 682609394-[4-(1-Benzofuran-5-yl)-2-methylphenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 36.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A microwaveable vial was charged with 4-(4-bromo-2-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.247 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (63.2 mg, 0.259 mmol), PdCl2(dppf) (9.03 mg, 0.012 mmol), K2CO3 (85 mg, 0.617 mmol), 1,4-dioxane (3 mL) and water (1 mL). The reaction was purged with nitrogen, sealed and heated in a microwave reactor at 150° C. for 30 min (LCMS indicated complete conversion of starting material to desired product). The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DMSO, filtered through a syringe filter and purified by reverse phase HPLC (Gilson, YMC-Pack ODS-A C18 5 μm 75×30 mm column, 10-90% MeCN/water+0.1% TFA, 3×1 mL injections). The appropriate fractions were concentrated to dryness and the residue was diluted with water (10 mL) and adjusted to pH 5 with conc. NH4OH. The resulting precipitate was collected by filtration and dried to constant weight under vacuum to provide the title product (40 mg, 0.090 mmol, 36.6% yield) as a white solid. MS(ES)+ m/e 443.1 [M+H]+.

Workup

  1. customThe reaction was purged with nitrogen
  2. customsealed
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in DMSO
  5. filtrationfiltered through a syringe
  6. filtrationfilter
  7. custompurified by reverse phase HPLC (Gilson, YMC-Pack ODS-A C18 5 μm 75×30 mm column, 10-90% MeCN/water+0.1% TFA, 3×1 mL injections)
  8. concentrationThe appropriate fractions were concentrated to dryness
  9. additionthe residue was diluted with water (10 mL)
  10. filtrationThe resulting precipitate was collected by filtration
  11. customdried to constant weight under vacuum

Sources & evidence

ORD record
ord-1dcd2953567d47a1b67ec7a7071c39cb
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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