Potassium Phosphate, Tribasic → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(4-imidazo[1,2-a]pyridin-7-ylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525135Notes

Reaction equation

HRID 525135 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.[N:25]1[CH:26]=[CH:27][N:28]2[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][C:29]=12.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:31]5[CH:32]=[CH:33][N:28]6[CH:27]=[CH:26][N:25]=[C:29]6[CH:30]=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 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneHCID 67375864Imidazo[1,2-a]pyridin-7-ylboronic acid

Product 1

HCID 533735525-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(4-imidazo[1,2-a]pyridin-7-ylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 51.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
95 °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), imidazo[1,2-a]pyridin-7-ylboronic acid (83 mg, 0.511 mmol), tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 0.026 mmol) and tripotassium phosphate (217 mg, 1.022 mmol) in absolute ethanol (5.0 mL) and water (5.00 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 95° C. for 6 h. The resulting yellow solution was evaporated in vacuo to a residue that was triturated in DMSO, filtered through a nylon syringe adapter, then purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA). The desired product fractions were combined, treated with saturated aqueous sodium bicarbonate and evaporated to a residue that was slurried in 5% MeOH in dichloromethane and filtered through a short pad of silica (˜2 g). The filtrate was evaporated in vacuo to afford the title compound as a tan solid (56 mg, 48.6%). MS(ES)+ m/e 429.0 [M+H]+.

Workup

  1. customthen purged with nitrogen
  2. customsealed with a standard teflon
  3. custom(crimped aluminum seal)
  4. customThe resulting yellow solution was evaporated in vacuo to a residue that
  5. customwas triturated in DMSO
  6. filtrationfiltered through a nylon syringe adapter
  7. custompurified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  8. additiontreated with saturated aqueous sodium bicarbonate
  9. customevaporated to a residue that
  10. filtrationfiltered through a short pad of silica (˜2 g)
  11. customThe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-7482e154002f4863914fe3cf5efd9791
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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