Ethanol → HCID 68452315, compound

HRID 2357600Notes

Reaction equation

HRID 2357600 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[N:7][N:6]=[CH:5]2.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].Br[C:42]1[S:46][C:45]([C:47]([O:49]C)=[O:48])=[CH:44][C:43]=1[CH3:51].C(=O)([O-])[O-].[K+].[K+].O.C(O)C>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].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>[CH3:51][C:43]1[CH:44]=[C:45]([C:47]([OH:49])=[O:48])[S:46][C:42]=1[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[N:7][N:6]=[CH:5]2

Participants

12

Reactant 7

HCID 702EthanolHCID 962WaterHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 2795489Methyl 5-bromo-4-methylthiophene-2-carboxylateHCID 251294786-Bromo-1-morpholinophthalazine

Product 1

HCID 68452315HCID 68452315, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Bromo-1-morpholinophthalazine (405 mg, 1377 μmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (524 mg, 2065 μmol), potassium acetate (541 mg, 5507 μmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (101 mg, 138 μmol) were dissolved in N,N-dimethylformamide (4.6 mL) and placed in the microwave for 10 min at 160° C. The reaction mixture was added to a vial containing methyl 5-bromo-4-methylthiophene-2-carboxylate (388 mg, 1652 μmol), tetrakis(triphenylphosphine)palladium (159 mg, 138 μmol), potassium carbonate-2 M in water (2754 μl, 5507 μmol), and ethanol (4590 μl, 1377 μmol). The vial was placed in the microwave for 10 min at 160° C., cooled, diluted with 75 mL of EtOAc, added to an addition funnel and partitioned with sodium bicarbonate (saturated, aqueous). The organic layer was washed 3× with 50 mL of sodium bicarbonate (saturated, aqueous), and separated. The aqueous layer was acidified to pH 4 with conc. HCl and extracted 3× with 50 mL of chloroform. The combined organic layers were dried over sodium sulfate, and concentrated via rotovap to give a crude product, which was purified by chromatography to obtain the title compound, as the TFA salt. Found MS (ES+): 356(M+H)+.

Workup

  1. additionThe reaction mixture was added to
  2. waitThe vial was placed in the microwave for 10 min at 160° C.
  3. temperaturecooled
  4. additionadded to an addition funnel
  5. custompartitioned with sodium bicarbonate (saturated, aqueous)
  6. washThe organic layer was washed 3× with 50 mL of sodium bicarbonate (saturated, aqueous)
  7. customseparated
  8. extractionextracted 3× with 50 mL of chloroform
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated via rotovap
  11. customto give a crude product, which
  12. customwas purified by chromatography

Sources & evidence

ORD record
ord-9e9288ce0a7d46179bb7a78878af1221
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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