Potassium Carbonate → HCID 68453940, compound

HRID 2357670Notes

Reaction equation

HRID 2357670 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]1[CH3:18])=[N:7][N:6]=[CH:5]2.[CH:19]1([NH:22][C:23](=[O:40])[C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[C:26](B3OC(C)(C)C(C)(C)O3)[CH:25]=2)[CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:19]1([NH:22][C:23](=[O:40])[C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]3[CH3:18])=[N:7][N:6]=[CH:5]4)[CH:25]=2)[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 27349382-(Dicyclohexylphosphino)-2'-methylbiphenylHCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 68453059HCID 68453059, compound

Product 1

HCID 68453940HCID 68453940, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-6-chloro-1-(2-methylpiperidin-1-yl)phthalazine (0.200 g, 0.76 mmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.474 g, 1.6 mmol), potassium carbonate (0.340 g, 2.5 mmol), 2-(dicyclohexylphosphino)-2′-methylbiphenyl (0.054 g, 0.15 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.045 g, 0.049 mmol) in 5 mL 80% aqueous degassed dioxane was heated at 80° C. for 15 h. The reaction was cooled to RT and partitioned between ethyl acetate/brine. The aqueous layer was extracted with ethyl acetate (3×) and the combined organic layers were concentrated onto silica gel and purified flash chromatography eluting with 2 M NH3 in MeOH:CH2Cl2 (0:1→1:24) to give a brown oil. The material was further purified by reverse-phase HPLC (Prodigy 5u ODS(3), 100A, 250×21.2) with 0.1% formic acid/H2O:0.1% formic acid/CH3CN (3:7→7:3) to give a white amorphous solid. Found MS m/z: 401.2 [M+1].

Workup

  1. customaqueous degassed dioxane
  2. temperatureThe reaction was cooled to RT
  3. custompartitioned between ethyl acetate/brine
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  5. concentrationthe combined organic layers were concentrated onto silica gel
  6. custompurified flash chromatography
  7. washeluting with 2 M NH3 in MeOH:CH2Cl2 (0:1→1:24)
  8. customto give a brown oil
  9. customThe material was further purified by reverse-phase HPLC (Prodigy 5u ODS(3), 100A, 250×21.2) with 0.1% formic acid/H2O
  10. custom0.1% formic acid/CH3CN (3:7→7:3) to give a white amorphous solid

Sources & evidence

ORD record
ord-5a0a5e9e28ed46c88377c730a75cf67a
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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