Dichloromethane → HCID 68379983, compound

HRID 1183835Notes

Reaction equation

HRID 1183835 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[CH:15]=[CH:14][CH:13]=[N:12][C:11]=13)[N:8]=[CH:7][N:6]([C@@H:16]1[C@@H:21]([OH:22])[CH2:20][CH2:19][O:18][CH2:17]1)[C:5]2=[O:23].C([O-])(=O)C.[K+].[B:29]1(B2OC(C)(C)C(C)(C)O2)[O:33]C(C)(C)C(C)(C)[O:30]1.ClCCl.[OH-].[Na+]>CN(C=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]>[OH:22][C@H:21]1[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]1[N:6]1[C:5](=[O:23])[C:4]2[C:9](=[C:10]3[CH:15]=[CH:14][CH:13]=[N:12][C:11]3=[C:2]([B:29]([OH:33])[OH:30])[CH:3]=2)[N:8]=[CH:7]1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 68379949HCID 68379949, compound

Product 1

HCID 68379983HCID 68379983, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a solution of 6-bromo-3-[(3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl]pyrido[2,3-h]quinazolin-4(3H)-one (1.00 g, 2.66 mmol) in 6 mL of DMF under an atmosphere of nitrogen was added potassium acetate (0.783 g, 7.97 mmol), bis(pinacolato)diboron (1.01 g, 3.99 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), 1:1 complex with dichloromethane (0.217 g, 0.266 mmol). The mixture was heated at 80° C. for 2 h, cooled to rt, and treated with 1 N aqueous sodium hydroxide to pH ˜9. The aqueous solution was washed 2× with dichloromethane, then treated with 10% aqueous potassium phosphate to pH ˜7. A brown solid was collected via filtration to provide {3-[(3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl]-4-oxo-3,4-dihyrdopyrido[2,3-h]quinazolin-6-yl}boronic acid that gave a mass ion (ES+) of 342.0 for [M+H]+.

Workup

  1. temperaturecooled to rt
  2. washThe aqueous solution was washed 2× with dichloromethane
  3. additiontreated with 10% aqueous potassium phosphate to pH ˜7
  4. filtrationA brown solid was collected via filtration

Sources & evidence

ORD record
ord-a435314f75b640b980ce5ada65ed0154
Source dataset
uspto-grants-2014_03
Patent number
US08664387B2

Reaction notes

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