Water → 4-Methyl-3-{1-[(3R)-3-methylmorpholin4-yl]phthalazin-6-yl}benzamide

HRID 2357652Notes

Reaction equation

HRID 2357652 reaction equation
[CH3:1][C@@H:2]1[CH2:7][O:6][CH2:5][CH2:4][NH:3]1.Br[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](Cl)=[N:14][N:13]=[CH:12]2.[CH3:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][C:22]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].O>C(OCC)(=O)C.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.CC1C=CC(C)=CC=1>[CH3:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][C:22]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]([N:3]1[CH2:4][CH2:5][O:6][CH2:7][C@H:2]1[CH3:1])=[N:14][N:13]=[CH:12]2

Participants

10

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 641498(R)-3-MethylmorpholineHCID 220304246-Bromo-1-chlorophthalazineHCID 595448534-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 684552244-Methyl-3-{1-[(3R)-3-methylmorpholin4-yl]phthalazin-6-yl}benzamide

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 7809P-XyleneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
165 °C

Procedure

To (R)-3-methylmorpholine (108 mg, 1068 μmol) and 6-bromo-1-chlorophthalazine (130 mg, 534 μmol) was added p-xylene (534 μl) and the mixture was heated to 165° C. for 1.5 h. The reaction mixture was added to 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (154 mg, 589 μmol), tetrakis(triphenylphosphine)palladium (31 mg, 27 μmol), ethanol (5.35 mL), and potassium carbonate—1.5 M in water (1428 μl, 2142 μmol) and heated to 90° C. for 1 h. It was cooled to RT, diluted with 50 mL of ethyl acetate, partitioned with sodium bicarbonate (saturated, aqueous), and the organics were washed 2×20 mL with sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, concentrated in vacuo, and purified by HPLC to give the title compound.

Workup

  1. temperatureheated to 90° C. for 1 h
  2. temperatureIt was cooled to RT
  3. custompartitioned with sodium bicarbonate (saturated, aqueous)
  4. washthe organics were washed 2×20 mL with sodium bicarbonate (saturated, aqueous)
  5. customseparated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by HPLC

Sources & evidence

ORD record
ord-b88bd8b83ce84d8fa1bfc141ddccf098
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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