Potassium Phosphate, Tribasic → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4'-(methyloxy)-4-biphenylyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525132Notes

Reaction equation

HRID 525132 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])=[CH:4][CH:3]=1.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:21]1([C:19]([N:16]2[CH2:17][CH2:18][C@@H:14]([CH2:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:30]5[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=5)=[CH:3][CH:4]=4)[C:9](=[O:24])[NH:10][N:11]=3)[CH2:15]2)=[O:20])[CH2:23][CH2:22]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 533715705-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4'-(methyloxy)-4-biphenylyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 72.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A vial was charged with a slurry of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.256 mmol), [4-(methyloxy)phenyl]boronic acid (78 mg, 0.511 mmol), tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 0.026 mmol) and tripotassium phosphate (217 mg, 1.022 mmol) in ethanol (4.0 mL) and water (4.00 mL) then purged with nitrogen and sealed with a standard teflon septa (crimped aluminum seal). The reaction was then heated in an aluminum block at 110° C. for 3 h. The resulting yellow slurry was diluted with ethanol then evaporated to dryness under reduced pressure. The residue was triturated from dichloromethane then the decanted solution was applied directly to a standard stock silica column (Analogix SF25-40 g) and eluted first with 100% ethyl acetate for 5 min and then with 7% methanol in dichloromethane. The combined desired fractions were evaporated to a colorless oil that was crystallized from hexanes/ethyl acetate to afford the title compound as a white solid (78 mg, 72.2%). MS(ES)+ m/e 419.2 [M+H]+.

Workup

  1. customthen purged with nitrogen
  2. customsealed with a standard teflon
  3. custom(crimped aluminum seal)
  4. additionThe resulting yellow slurry was diluted with ethanol
  5. customthen evaporated to dryness under reduced pressure
  6. customThe residue was triturated from dichloromethane
  7. washeluted first with 100% ethyl acetate for 5 min
  8. customwere evaporated to a colorless oil that
  9. customwas crystallized from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-3debd2a2b96143018d8a4ae5dafeaa53
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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