Potassium Phosphate, Tribasic → HCID 178466665, compound

HRID 230187Notes

Reaction equation

HRID 230187 reaction equation
[F:1][C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[N:10]=[C:9]2[NH:11][N:12]=[C:13](I)[C:8]2=[C:7]([NH:15][CH2:16][CH:17]([OH:19])[CH3:18])[N:6]=1.[F:25][C:26]1[CH:27]=[CH:28][C:29]([O:35][CH2:36][CH3:37])=[C:30](B(O)O)[CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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.C(Cl)Cl.O1CCOCC1>[F:1][C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[N:10]=[C:9]2[NH:11][N:12]=[C:13]([C:28]3[CH:27]=[C:26]([F:25])[CH:31]=[CH:30][C:29]=3[O:35][CH2:36][CH3:37])[C:8]2=[C:7]([NH:15][CH2:16][C@H:17]([OH:19])[CH3:18])[N:6]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 16217479(2-Ethoxy-5-fluorophenyl)boronic acidHCID 178468251HCID 178468251, compound

Product 1

HCID 178466665HCID 178466665, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 178478470HCID 178478470, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
180 °C

Procedure

1-[6-(2,4-Difluoro-phenoxy)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol (200 mg, 0.447 mmol), 5-fluoro-2-ethoxyphenyl boronic acid (246 mg), K3PO4 (285 mg), and Tetrakis(triphenylphosphine)palladium(0) CH2Cl2 (73 mg) were added to 2 mL dioxane in a microwave vial. The vial was sealed and the reaction mixture was heated to 180° C. for 10 minutes. The reaction mixture was partitioned between water and ethyl acetate, and the organic layer was separated, dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was filtered through silica gel using 10% MeOH in methylene chloride, then purified by preparative scale thin layer chromatography using 10% MeOH in methylene chloride, to give 62.9 mg of (R)-1-[6-(2,4-Difluoro-phenoxy)-3-(2-ethoxy-5-fluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol. Mass Spec. M+H=460.

Workup

  1. customThe vial was sealed
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. customthe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. filtrationThe residue was filtered through silica gel using 10% MeOH in methylene chloride
  8. custompurified by preparative scale thin layer chromatography

Sources & evidence

ORD record
ord-591c1ac235724447b9f829e3b10ba326
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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