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

HRID 525133Notes

Reaction equation

HRID 525133 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.[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)#[N:26].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]([C:25]#[N:26])=[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 27343264-Cyanophenylboronic acidHCID 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 533735544'-(3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-4-biphenylcarbonitrileYield 28.3%

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-cyanophenyl)boronic acid (75 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 2 h. The resulting yellow slurry was diluted with ethanol, treated with silica powder (2 g) then evaporated under reduced pressure. The dried powder was placed in a column adaptor (Analogix Dasi adapter) attached to a standard stock silica column (Analogix SF25-40 g) and eluted with ethyl acetate for 10 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 (30 mg, 28.1%). MS(ES)+ m/e 414.2 [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. additiontreated with silica powder (2 g)
  6. customthen evaporated under reduced pressure
  7. washeluted with ethyl acetate for 10 min
  8. customwere evaporated to a colorless oil that
  9. customwas crystallized from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-c1ceb615f35147fbb1ef6e35babb04a9
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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