Potassium Phosphate, Tribasic → HCID 178469763, compound

HRID 593702Notes

Reaction equation

HRID 593702 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:8]=[CH:9][CH:10]=2)[C:5](Cl)=[N:4][N:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][CH:30]=[C:31]([CH:37]=2)[C:32]([O:34][CH2:35][CH3:36])=[O:33])O1.[O-:39]P([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1([PH+](C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.O.C([O-])=O.[NH4+].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]>[OH:39][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][C:7]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:2]([C:27]2[CH:28]=[N:29][CH:30]=[C:31]([CH:37]=2)[C:32]([O:34][CH2:35][CH3:36])=[O:33])=[N:3][N:4]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 3816953Ethyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxylateHCID 11710396Tricyclohexylphosphonium TetrafluoroborateHCID 904244121,4-Dichloro-5-phenylphthalazine

Product 1

HCID 178469763HCID 178469763, compoundYield 51.8%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 2723923Ammonium formateSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 1,4-dichloro-5-phenylphthalazine (5.00 g, 18.2 mmol) in 1,4-dioxane (50 mL) and water (9 mL) was added ethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (5.32 g, 27.3 mmol), and K3PO4 (7.72 g, 36.3 mmol). The contents were purged with nitrogen for 10 min. Tricyclohexylphosphonium tetrafluoroborate (0.402 g, 1.09 mmol) was added followed by Pd2(dba)3 (0.416 g, 0.454 mmol) and the reaction mixture was heated at 95° C. for 12 h. The reaction mixture was allowed to cool to ambient temperature and diluted with HCOONH4 buffer (pH˜5) solution. The reaction mixture was extracted with EtOAc (3×75 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was triturated with EtOAc to afford ethyl 5-(4-hydroxy-5-phenylphthalazin-1-yl)nicotinate (3.50 g, 44.1%) as an off-white solid which is 85% pure by LC-MS. LCMS (Condition 1): retention time 2.52 min, [M+1]=372.0. 1H NMR (400 MHz, DMSO-d6) δ 1.37 (t, J=7.2 Hz, 3 H), 4.41 (q, J=7.2 Hz, 2 H), 7.33-7.42 (m, 5 H), 7.62-7.65 (m, 2 H), 7.92 (dd, J=7.6 Hz, J=8.0 Hz, 1 H), 8.49 (t, J=2.0 Hz, 1 H), 9.07 (d, J=2.0 Hz, 1 H), 9.25 (d, J=2.0 Hz, 1 H), 12.74 (br s, 1 H).

Workup

  1. customThe contents were purged with nitrogen for 10 min
  2. temperatureto cool to ambient temperature
  3. extractionThe reaction mixture was extracted with EtOAc (3×75 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was triturated with EtOAc

Sources & evidence

ORD record
ord-b159a69123c8400baa6d818e58940d52
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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