Potassium Carbonate → 3-(5-Cyclopropyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-1H-indol-5-yl)-2-pyridinamine

HRID 632464Notes

Reaction equation

HRID 632464 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[O:10][C:11]([CH:14]3[CH2:16][CH2:15]3)=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][C:29](B(O)O)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1>O1CCOCC1.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:14]1([C:11]2[O:10][C:9]([C:4]3[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:29]4[CH:28]=[C:27]5[C:32](=[CH:31][CH:30]=4)[N:24]([CH3:23])[CH:25]=[CH:26]5)[CH:3]=3)=[N:13][N:12]=2)[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27598671-Methyl-1H-indole-5-boronic acidHCID 902729865-Bromo-3-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-2-pyridinamine

Product 1

HCID 902773103-(5-Cyclopropyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-1H-indol-5-yl)-2-pyridinamine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-3-(5-cyclopropyl-[1,3,4]oxadiazol-2-yl)-pyridin-2-ylamine (500 mg, 1.77 mmol) in dioxane (15.0 mL) and water (5.0 mL) were added K2CO3 (730 mg, 5.31 mmol) and N-methylindole-5-boronic acid (140 mg, 1.95 mmol) in a sealed tube. The reaction mixture was degassed with argon for 20 min, then Pd(PPh3)4 (100 mg, 0.088 mmol) was added and stirred for 18 h at 100° C. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3×20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude title compound. Crude product was purified by column chromatography using 100-200 mesh silica gel and compound was eluted with 40% ethyl acetate in petroleum ether to afford the title compound.

Workup

  1. customThe reaction mixture was degassed with argon for 20 min
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customto get crude title compound
  7. customCrude product was purified by column chromatography
  8. washwas eluted with 40% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-90a16d6ef527469a817114896cd227c5
Source dataset
uspto-grants-2016_04
Patent number
US09321748B2

Reaction notes

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