Sodium Carbonate → HCID 10225311, compound

HRID 1839144Notes

Reaction equation

HRID 1839144 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[CH:35]([NH:38][C:39]([C:41]1[C:50](=[O:51])[C:49]2[C:44](=[N:45][CH:46]=[CH:47][CH:48]=2)[N:43]([C:52]2[CH:57]=[CH:56][CH:55]=[C:54](Br)[CH:53]=2)[CH:42]=1)=[O:40])([CH3:37])[CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)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]>[CH:35]([NH:38][C:39]([C:41]1[C:50](=[O:51])[C:49]2[C:44](=[N:45][CH:46]=[CH:47][CH:48]=2)[N:43]([C:52]2[CH:53]=[CH:54][CH:55]=[C:56]([C:2]3[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=3)[CH:57]=2)[CH:42]=1)=[O:40])([CH3:37])[CH3:36]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 959915'-Bromo-2'-hydroxyacetophenoneHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 129913181-(3-bromophenyl)-N-isopropyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide

Product 1

HCID 10225311HCID 10225311, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of 5′-bromo-2′-hydroxyacetophenone, diboron pinacol ester (1.25 eq), potassium acetate (3 eq) and [1,1′-bis (diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq) in N,N-dimethylformamide (10 ml/mmol) was stirred at 80° C. for 3 hours and cooled down. A solution of N-Isopropyl-1-(3-bromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide from Example 1, Step 4 (0.75 eq) in N,N-dimethylformamide (7 ml/mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq) and 2M aqueous sodium carbonate (8.5 eq) were added and the resulting mixture was stirred at 80° C. for 2.5 hours. The cooled mixture was partitioned between ethyl acetate and water and the product from the organic phase was chromatographed on silica gel eluting with 60% ethyl acetate in hexane to afford the title compound as a light yellow solid.

Workup

  1. temperaturecooled down
  2. stirringthe resulting mixture was stirred at 80° C. for 2.5 hours
  3. customThe cooled mixture was partitioned between ethyl acetate and water
  4. customthe product from the organic phase was chromatographed on silica gel eluting with 60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f7b08f72c30a4e528a41f2cede12445c
Source dataset
uspto-grants-2004_01
Patent number
US06677351B2

Reaction notes

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