Water → 4-Chloro-3-(1-morpholin-4-ylphthalazin-6-yl)benzamide

HRID 2357636Notes

Reaction equation

HRID 2357636 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.[Cl:41][C:42]1[CH:50]=[CH:49][C:45]([C:46]([NH2:48])=[O:47])=[CH:44][C:43]=1I.C(=O)([O-])[O-].[K+].[K+].O>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].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(O)C.O1CCOCC1>[Cl:41][C:42]1[CH:50]=[CH:49][C:45]([C:46]([NH2:48])=[O:47])=[CH:44][C:43]=1[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

Participants

12

Reactant 6

HCID 962WaterHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 221155764-Chloro-3-iodobenzamideHCID 251294786-Bromo-1-morpholinophthalazine

Product 1

HCID 684567284-Chloro-3-(1-morpholin-4-ylphthalazin-6-yl)benzamide

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 6-Bromo-1-morpholinophthalazine (0.20 g, 680 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (50 mg, 68 μmol), potassium acetate (200 mg, 2040 μmol), and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (207 mg, 816 μmol) was added 1,4-dioxane (6.80 mL) and the mixture was heated to 80° C. for 2 h. The mixture was added to a sealed tube containing 4-chloro-3-iodobenzamide (230 mg, 816 μmol), tetrakis(triphenylphosphine)palladium (79 mg, 68 μmol), potassium carbonate—1.5 M in water (1.81 μl, 2.72 mmol), and ethanol (6.80 mL) and heated to 110° C. for 2 h. After cooling the reaction mixture was diluted with 75 mL of ethyl acetate, added to a separation funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 3 times 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.

Workup

  1. additionThe mixture was added to a sealed tube
  2. temperatureheated to 110° C. for 2 h
  3. temperatureAfter cooling the reaction mixture
  4. additionadded to a separation funnel
  5. custompartitioned with sodium bicarbonate (saturated, aqueous)
  6. washwashed 3 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  7. customseparated
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. custompurified by HPLC

Sources & evidence

ORD record
ord-ac43cb98b6b340debbd465fa1b976610
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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