Water → 4-chloro-N-cyclopropyl-3-(1-morpholinophthalazin-6-yl)benzamide

HRID 2357591Notes

Reaction equation

HRID 2357591 reaction equation
[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([NH:8][CH:9]2[CH2:11][CH2:10]2)=[O:7])=[CH:4][C:3]=1I.C([O-])(=O)C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.Br[C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[C:45]([N:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1)=[N:44][N:43]=[CH:42]2.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.CCOC(C)=O.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>[Cl:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([NH:8][CH:9]2[CH2:11][CH2:10]2)=[O:7])=[CH:4][C:3]=1[C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[C:45]([N:49]1[CH2:50][CH2:51][O:52][CH2:53][CH2:54]1)=[N:44][N:43]=[CH:42]2

Participants

12

Reactant 6

HCID 962WaterHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 251294786-Bromo-1-morpholinophthalazineHCID 397175964-chloro-N-cyclopropyl-3-iodoBenzamide

Product 1

HCID 684528354-chloro-N-cyclopropyl-3-(1-morpholinophthalazin-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
180 °C

Procedure

4-Chloro-N-cyclopropyl-3-iodobenzamide (190 mg, 591 μmol), potassium acetate (174mg, 1773 μmol), bis(pinacolato)diboron (165 mg, 650 μmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (43 mg, 59 μmol) were suspended in dioxane (3.9 mL) and placed in the microwave for 10 min at 180° C. before being added to a mixture of 6-bromo-1-morpholinophthalazine (120 mg, 408 μmol), sodium carbonate-2 M in water (1.2 mL, 2.4 mmol), tetrakis(triphenylphosphine)palladium (68 mg, 59 μmol), and ethyl alcohol (3.9 mL). The combined mixture was heated in the microwave for 10 min at 180° C. The reaction mixture was diluted with 20 mL of EtOAc, added to an addition funnel, and partitioned with sodium bicarbonate (saturated, aqueous). The organic layers were combined, washed 3 times with 20 mL of sodium bicarbonate (saturated, aqueous), separated, combined, dried over sodium sulfate, and concentrated via rotovap to give a crude product. After purification by chromatography, the title compound was obtained. Found MS (ES+): 409 (M+H)+.

Workup

  1. additionadded to an addition funnel
  2. custompartitioned with sodium bicarbonate (saturated, aqueous)
  3. washwashed 3 times with 20 mL of sodium bicarbonate (saturated, aqueous)
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated via rotovap
  7. customto give a crude product
  8. customAfter purification by chromatography

Sources & evidence

ORD record
ord-32179c94fc064db3ba799b286e2ca68e
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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