Sodium Carbonate → HCID 24986037, compound

HRID 388151Notes

Reaction equation

HRID 388151 reaction equation
[O:1]=[C:2]1[NH:18][C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=3)[N:9]=[C:4]2[N:3]1[CH2:19][CH2:20][CH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.Br[C:28]1[N:33]=C2N(CCC3CCOCC3)C(=O)NC2=N[CH:29]=1.C(C1C=CC(B(O)O)=CC=1)#[N:47].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O>[CH3:29][C:28]1[NH:33][N:47]=[C:14]([C:13]2[CH:12]=[CH:11][C:10]([C:8]3[N:9]=[C:4]4[N:3]([CH2:19][CH2:20][CH:21]5[CH2:26][CH2:25][O:24][CH2:23][CH2:22]5)[C:2](=[O:1])[NH:18][C:5]4=[N:6][CH:7]=3)=[CH:17][CH:16]=2)[N:15]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 66699930HCID 66699930, compoundHCID 86626416HCID 86626416, compound

Product 1

HCID 24986037HCID 24986037, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-(2-Oxo-3-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzonitrile. 6-Bromo-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 108.B) (2.5 g, 7.60 mmol), 4-cyanophenylboronic acid (1.69 g, 11.5 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferocene]palladium (II) dichloromethane (0.62 g, 0.70 mmol) were combined in dioxane (10 mL). Sodium carbonate (0.91 g, 15.2 mmol) in water (10 mL) was added and the reaction stirred at 100° C. overnight. The cooled reaction solution was filtered through Celite and the filter cake was washed with ethyl acetate. Filtrate and ethyl acetate wash were combined and solvent removed under reduced pressure. The resulting material was purified using reverse-phase preparatory HPLC (20-80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). Fractions containing clean product were passed through a Phenomenex Strata-X-C ion exchange column to remove TFA. The column was washed successively with water, methanol, and then 5% ammonium hydroxide in methanol. The product was released with the 5% ammonium hydroxide in methanol eluent and was concentrated on a rotary evaporator. The residue was triturated with ethyl ether in hexane to give a fine powder and dried under vacuum at 50° C. to give the desired product (1.2 g, 46%) as a white solid. MS (ESI) m/z 350.0 [M+1]+.

Workup

  1. customThe cooled reaction solution
  2. filtrationwas filtered through Celite
  3. washthe filter cake was washed with ethyl acetate
  4. washFiltrate and ethyl acetate wash
  5. customsolvent removed under reduced pressure
  6. customThe resulting material was purified
  7. customreverse-phase preparatory HPLC (20-80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  8. additionFractions containing clean product
  9. customto remove TFA
  10. washThe column was washed successively with water, methanol
  11. concentrationwas concentrated on a rotary evaporator
  12. customThe residue was triturated with ethyl ether in hexane
  13. customto give a fine powder
  14. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-523cc765e70d480c92ba8bc7910c819f
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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