Acetonitrile → HCID 86732441, compound

HRID 1776412Notes

Reaction equation

HRID 1776412 reaction equation
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[C:20]([OH:30])=[CH:19][N:18]=3)=[N:9]2)=[CH:5][CH:4]=1.FC(F)(F)S(O[CH2:39][C:40]([F:43])([F:42])[F:41])(=O)=O.C(=O)([O-])[O-].[K+].[K+].C(#N)C>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[C:20]([O:30][CH2:39][C:40]([F:43])([F:42])[F:41])=[CH:19][N:18]=3)=[N:9]2)=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 136271303HCID 136271303, compound

Product 1

HCID 86732441HCID 86732441, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

143 mg of 2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol (3-2, 0.337 mmol, 1. eq.) were dissolved in 500 μl of dry DMF. Then 117 mg of 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.505 mmol, 1.5 eq.), 93.1 mg of potassium carbonate (0.674 mmol, 2 eq.) and 24 μl of acetonitrile were added. The resulting mixture was stirred at 150° C. for 30 minutes in a microwave. Then the mixture was partitioned between water and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography and preparative TLC to yield 7.7 mg (0.01 mmol, 3.9%) of the analytically pure target compound.

Workup

  1. customThen the mixture was partitioned between water and dichloromethane/isopropanol 4:1
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over a silicone
  6. filtrationfilter
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography and preparative TLC
  9. customto yield 7.7 mg (0.01 mmol, 3.9%) of the analytically pure target compound

Sources & evidence

ORD record
ord-2865516537224ea6ba3179fc07755439
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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