Potassium Acetate → (S)-1-(3-methylmorpholino)phthalazin-6-ylboronic acid

HRID 2357523Notes

Reaction equation

HRID 2357523 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][C@@H:13]1[CH3:18])=[N:7][N:6]=[CH:5]2.[B:19]1(B2OC(C)(C)C(C)(C)O2)[O:23]C(C)(C)C(C)(C)[O:20]1.C([O-])(=O)C.[K+]>CN(C=O)C.C(OCC)(=O)C.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]>[CH3:18][C@@H:13]1[N:12]([C:8]2[C:9]3[C:4](=[CH:3][C:2]([B:19]([OH:23])[OH:20])=[CH:11][CH:10]=3)[CH:5]=[N:6][N:7]=2)[CH2:17][CH2:16][O:15][CH2:14]1

Participants

7

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 25129828(s)-6-Bromo-1-(3-methylmorpholino)phthalazine

Product 1

HCID 68455585(S)-1-(3-methylmorpholino)phthalazin-6-ylboronic acid

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

A mixture of (S)-6-bromo-1-(3-methylmorpholino)phthalazine (1.60 g, 5.2 mmol), bis(pinacolato)diboron (2.0 g, 7.8 mmol) and potassium acetate (2.5 g, 26 mmol) in DMF (25 mL) was degassed with N2 for 20 min. It was then treated with 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (0.38 g, 0.52 mmol). The reaction mixture was stirred at 85° C. under nitrogen for 18 h. After cooling to ambient, the reaction mixture was diluted with ethyl acetate (50 mL, and filtered through a Celite® pad, and rinsed with additional ethyl acetate (2×10 mL). The filtrate was concentrated. The residue was treated with diethyl ether (50 mL) and 1 N aqueous HCl (50 mL), and then filtered through a Celite pad. The filtrate was transferred to a separatory funnel, the aqueous phase was separated, concentrated under vacuum and the brown residue was purified on a reversed phased HPLC (5-90% [0.1% TFA in acetonitrile] in [0.1% TFA in water]) to give (S)-1-(3-methylmorpholino)phthalazin-6-ylboronic acid as a light yellow amorphous solid. MS (ESI, pos.ion) m/z: 274.0 (M+1).

Workup

  1. customwas degassed with N2 for 20 min
  2. temperatureAfter cooling to ambient, the reaction mixture
  3. filtrationfiltered through a Celite® pad
  4. washrinsed with additional ethyl acetate (2×10 mL)
  5. concentrationThe filtrate was concentrated
  6. additionThe residue was treated with diethyl ether (50 mL) and 1 N aqueous HCl (50 mL)
  7. filtrationfiltered through a Celite pad
  8. customThe filtrate was transferred to a separatory funnel
  9. customthe aqueous phase was separated
  10. concentrationconcentrated under vacuum
  11. customthe brown residue was purified on

Sources & evidence

ORD record
ord-e94a35e63b4e40c586d66445bd8048cc
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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