Water → HCID 68454714, compound

HRID 2357642Notes

Reaction equation

HRID 2357642 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.[CH:20]1([NH:23][C:24](=[O:41])[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:26]=2)[CH2:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+].O>CC1C=CC(C)=CC=1.C(O)C.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>[CH:20]1([NH:23][C:24](=[O:41])[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([C:9]3[CH:10]=[C:11]4[C:16](=[CH:17][CH:18]=3)[C:15]([N:3]3[CH2:4][CH2:5][O:6][CH2:7][C@H:2]3[CH3:1])=[N:14][N:13]=[CH:12]4)[CH:26]=2)[CH2:21][CH2:22]1

Participants

10

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 641498(R)-3-MethylmorpholineHCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 220304246-Bromo-1-chlorophthalazine

Product 1

HCID 68454714HCID 68454714, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
165 °C

Procedure

(R)-3-Methylmorpholine (93 mg, 919 μmol) was dissolved in p-xylene (0.460 mL) before 6-bromo-1-chlorophthalazine (112 mg, 460 μmol) was added. The reaction mixture was heated to 165° C. for 1.5 h, then diluted with ethyl alcohol (4.61 mL) before N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (153 mg, 507 μmol), tetrakis(triphenylphosphine)palladium (27 mg, 23 μmol), and potassium carbonate—1.5 M in water (1229 μl, 1843 μmol) were added. The mixture was heated to 90° C. for 1 h, diluted with 50 mL of ethyl acetate, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2 times with 20 mL of sodium bicarbonate (saturated, aqueous) and separated. The organic layers were dried over sodium sulfate, concentrated, and purified by flash chromatography to give the title compound. MS (ES+): 403(M+H)+.

Workup

  1. additionwas added
  2. additionwere added
  3. temperatureThe mixture was heated to 90° C. for 1 h
  4. additionadded to a separatory funnel
  5. custompartitioned with sodium bicarbonate (saturated, aqueous)
  6. washwashed 2 times with 20 mL of sodium bicarbonate (saturated, aqueous)
  7. customseparated
  8. dry with materialThe organic layers were dried over sodium sulfate
  9. concentrationconcentrated
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-750d3430391543e6bd8d4fe030fcfaf8
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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