Water → N-(2-methoxy-5-(trifluoromethyl)phenyl)-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide

HRID 2357596Notes

Reaction equation

HRID 2357596 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[CH3:23])[C:5]([NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[CH:10][C:9]=1[O:18][CH3:19])=[O:6].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:48]1[CH:49]=[C:50]2[C:55](=[CH:56][CH:57]=1)[C:54]([N:58]1[CH2:63][CH2:62][O:61][CH2:60][CH2:59]1)=[N:53][N:52]=[CH:51]2.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.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].[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.C(O)C>[CH3:19][O:18][C:9]1[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=1[NH:7][C:5](=[O:6])[C:4]1[CH:20]=[CH:21][C:22]([CH3:23])=[C:2]([C:48]2[CH:49]=[C:50]3[C:55](=[CH:56][CH:57]=2)[C:54]([N:58]2[CH2:59][CH2:60][O:61][CH2:62][CH2:63]2)=[N:53][N:52]=[CH:51]3)[CH:3]=1

Participants

12

Reactant 6

HCID 962WaterHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 251294786-Bromo-1-morpholinophthalazineHCID 684551813-Iodo-N-(2-methoxy-5-(trifluoromethyl)phenyl)-4-methylbenzamide

Product 1

HCID 68452508N-(2-methoxy-5-(trifluoromethyl)phenyl)-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Iodo-N-(2-methoxy-5-(trifluoromethyl)phenyl)-4-methylbenzamide (205 mg, 471 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (34 mg, 47 μmol), bis(pinacolato)diboron (179 mg, 707 μmol), and potassium acetate (118 μL, 1884 μmol) were dissolved/suspended in dimethylformamide (2.4 mL) and placed in the microwave at 160° C. for 10 min. The reaction mixture was then transferred to another vial containing 6-bromo-1-morpholinophthalazine (125mg, 424 μmol), tetrakis(triphenylphosphine) palladium(0)(54 mg, 47 μmol), potassium carbonate-2 M in water (942 μL, 1884 μmol), and ethanol (2.4 mL). The combined mixture was reacted in a microwave oven at 160° C. for 10 min. The reaction mixture was diluted with 50 mL of EtOAc, added to an addition funnel and partitioned with sodium bicarbonate (saturated, aqueous). The organic layer was washed 3 times with 50 mL of sodium bicarbonate (saturated, aqueous), dried over sodium sulfate, and concentrated via rotovap to give a crude product. The crude product was purified by chromatography to obtain the title compound. Found MS (ES+): 523(M+H)+.

Workup

  1. customThe combined mixture was reacted in a microwave oven at 160° C. for 10 min
  2. additionadded to an addition funnel
  3. custompartitioned with sodium bicarbonate (saturated, aqueous)
  4. washThe organic layer was washed 3 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated via rotovap
  7. customto give a crude product
  8. customThe crude product was purified by chromatography

Sources & evidence

ORD record
ord-4f8a758e0f514bbe9508c63d4623b1c3
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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