Potassium Hydroxide → HCID 86732440, compound

HRID 1776411Notes

Reaction equation

HRID 1776411 reaction equation
[CH2:1]([O:3][C:4]1[CH:33]=[C:32]([F:34])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[C:21]([OH:31])=[CH:20][N:19]=3)=[N:10]2)=[C:6]([F:35])[CH:5]=1)[CH3:2].[OH-].[K+].Cl[C:39]([F:49])([F:48])C(C1C=CC=CC=1)=O>C(#N)C>[F:48][CH:39]([F:49])[O:31][C:21]1[C:22]([NH:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)=[N:23][C:18]([C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:9]([CH2:8][C:7]3[C:6]([F:35])=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[CH:33][C:32]=3[F:34])[N:10]=2)=[N:19][CH:20]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 2382962-Chloro-2,2-difluoroacetophenoneHCID 136271309HCID 136271309, compound

Product 1

HCID 86732440HCID 86732440, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
-75 °C

Procedure

100 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol (3-1, 0.211 mmol, 1. eq.) were suspended in 843 μl of 30% aq. potassium hydroxide solution (5.72 mmol, 27 eq.) and 843 μl of acetonitrile. The suspension was cooled with a freezing mixture to −75° C. 93 μl of 2-chloro-2,2-difluoro-1-phenylethanone (0.632 mmol, 3 eq.) were added dropwise. The freezing mixture was removed. The reaction mixture was stirred at 80° C. bath temperature for 4 hours. 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. Preparative HPLC purification provided 4 mg (0.01 mmol, 3.2%) of the analytically pure target compound.

Workup

  1. customThe freezing mixture was removed
  2. customThen the mixture was partitioned between water and dichloromethane/isopropanol 4:1
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over a silicone
  7. filtrationfilter
  8. concentrationconcentrated in vacuo
  9. customPreparative HPLC purification
  10. customprovided 4 mg (0.01 mmol, 3.2%) of the analytically pure target compound

Sources & evidence

ORD record
ord-2bbd013294d144cfb206a298cd605eca
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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