Sodium Hydroxide → HCID 56655888, compound

HRID 449642Notes

Reaction equation

HRID 449642 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[N:15][C:14]([O:17][CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[C:65]([C:69]1[CH:70]=[C:71]2[C:76](=[C:77]([F:79])[CH:78]=1)[C:75](=[O:80])[N:74]([C:81]1[CH:91]=[CH:90][CH:89]=[C:88](B3OC(C)(C)C(C)(C)O3)[C:82]=1[CH2:83][O:84]C(=O)C)[N:73]=[CH:72]2)([CH3:68])([CH3:67])[CH3:66].[OH-].[Na+]>C(O)CCC.O.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[C:65]([C:69]1[CH:70]=[C:71]2[C:76](=[C:77]([F:79])[CH:78]=1)[C:75](=[O:80])[N:74]([C:81]1[CH:91]=[CH:90][CH:89]=[C:88]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[N:15][C:14]([O:17][CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=3)[C:82]=1[CH2:83][OH:84])[N:73]=[CH:72]2)([CH3:68])([CH3:66])[CH3:67]

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 66742927HCID 66742927, compound

Product 1

HCID 56655888HCID 56655888, compoundYield 48.1%

Reagents, catalysts & solvents 4

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 2631-ButanolSolventHCID 962WaterSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

In a 15 mL microwave reaction vial was added 6-chloro-4-[5-(2-dimethylamino-ethoxy)-pyrazin-2-ylamino]-2-methyl2H-pyridazin-3-one (89 mg, 274 μmol, Eq: 1.00) in 7 mL n-butanol and 1.4 mL water. To the solution was added potassium phosphate tribasic (128 mg, 603 μmol), X-PHOS (19.6 mg, 41.1 μmol, Eq: 0.15) and acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (279 mg, 395 μmol, Eq: 1.44) with stirring and bubbling of argon. To this mixture was added bis(dibenzylideneacetone)palladium (11.8 mg, 20.6 μmol, Eq: 0.075) and the reaction was heated at 110° C. for 3 hrs. The reaction was cooled to room temperature and treated with a solution of NaOH (220 mg) in water (1.5 mL). The resultant mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with DCM (50 mL) and water (50 mL). The organic phase was separated, washed with water (30 mL) and concentrated. The residue was purified on silica gel with 0-10% (10% NH4OH in MeOH) in ( 1/1) EtOAc/Hex. The pure fractions were concentrated and dissolved in DCM. Heptane was added to precipitate the product. The liquid was decanted off to afford 81 mg (46%) of the title compound as an off white solid. mp: 185-190° C.

Workup

  1. customIn a 15 mL microwave reaction
  2. custombubbling of argon
  3. temperatureThe reaction was cooled to room temperature
  4. customThe organic phase was separated
  5. washwashed with water (30 mL)
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel with 0-10% (10% NH4OH in MeOH) in ( 1/1) EtOAc/Hex
  8. concentrationThe pure fractions were concentrated
  9. dissolutiondissolved in DCM
  10. additionHeptane was added
  11. customto precipitate the product
  12. customThe liquid was decanted off

Sources & evidence

ORD record
ord-91ba574a5f944e168374ce582b7fcd4f
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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