Water → HCID 25129831, compound

HRID 2357629Notes

Reaction equation

HRID 2357629 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[N:7][N:6]=[CH:5]2.C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.[CH:41]1([NH:44][C:45](=[O:53])[C:46]2[CH:51]=[CH:50][CH:49]=[C:48](I)[CH:47]=2)[CH2:43][CH2:42]1.O>C(O)C.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1>[CH:41]1([NH:44][C:45](=[O:53])[C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:7][N:6]=[CH:5]4)[CH:47]=2)[CH2:42][CH2:43]1

Participants

12

Reactant 5

HCID 962WaterHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 16388679HCID 16388679, compoundHCID 251294786-Bromo-1-morpholinophthalazine

Product 1

HCID 25129831HCID 25129831, compound

Reagents, catalysts & solvents 6

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 11430Potassium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 6-bromo-1-morpholinophthalazine (95 mg, 323 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (24 mg, 32 μmol), potassium acetate (95 mg, 969 μmol), and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (90 mg, 355 μmol) was added 1,4-dioxane (3.23 mL) before it was heated to 80° C. for 2.5 h. This reaction mixture was added to a mixture of N-cyclopropyl-3-iodobenzamide (111 mg, 388 μmol) and tetrakis(triphenylphosphine) palladium (37 mg, 32 μmol) in ethanol (3.23 mL) and potassium carbonate −1.5 M in water (861 μl, 1292 μmol) and stirred for 2 h at 80° C. The mixture was diluted with 75 mL of ethyl acetate, added to a separation funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2× with 50 mL of sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, concentrated in vacuo, and purified by HPLC to give the title compound. MS (ES+): 375 (M+H)+.

Workup

  1. additionadded to a separation funnel
  2. custompartitioned with sodium bicarbonate (saturated, aqueous)
  3. washwashed 2× with 50 mL of sodium bicarbonate (saturated, aqueous)
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by HPLC

Sources & evidence

ORD record
ord-20a4cdb40dab44bebb34bb9eb2755714
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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