Sodium Carbonate → 2-(trans)-{3'-[3-[(Cyclopropylamino)carbonyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]-1,1'-biphenyl-4-yl}cyclopropanecarboxylic Acid

HRID 1294363Notes

Reaction equation

HRID 1294363 reaction equation
C[C:2]([C:4]1[C:13](=O)[N:12]([CH3:15])[C:11]2[N:10]=[C:9](C3C=CC(Cl)=CC=3Cl)[C:8](C3C=CC(Cl)=CC=3)=[CH:7][C:6]=2[C:5]=1NC(C)=O)=[O:3].CC1(C)C(C)(C)OB([C:43]2[CH:48]=[CH:47][C:46]([C@@H:49]3[CH2:51][C@H:50]3[C:52]([OH:54])=[O:53])=[CH:45][CH:44]=2)O1.C([O-])([O-])=[O:57].[Na+].[Na+].C1C=CC(P([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77]C=2)C2C=CC=CC=2)=CC=1.[CH2:81](O)[CH2:82]C.C[N:86]([CH:88]=O)C>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:88]1([NH:86][C:2]([C:4]2[C:5](=[O:57])[C:6]3[C:11](=[N:10][CH:9]=[CH:8][CH:7]=3)[N:12]([C:15]3[CH:75]=[C:80]([C:43]4[CH:44]=[CH:45][C:46]([C@@H:49]5[CH2:51][C@H:50]5[C:52]([OH:54])=[O:53])=[CH:47][CH:48]=4)[CH:79]=[CH:78][CH:77]=3)[CH:13]=2)=[O:3])[CH2:82][CH2:81]1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 11386747NaphthyridinoneHCID 674947362-(trans)-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarboxylic AcidHCID 86598119Dimethylformamide n-propanol

Product 1

HCID 566799692-(trans)-{3'-[3-[(Cyclopropylamino)carbonyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]-1,1'-biphenyl-4-yl}cyclopropanecarboxylic Acid

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of NAPHTHYRIDINONE 2 (1.0 eq), acid from step 3 (1.5 eq), Na2CO3 (3.5 eq; 2M in H2O), Pd(OAc)2 (0.05 eq.) and PPh3 (0.15 eq.) or PdCl2dppf (0.05 eq) in n-propanol-DMF (1:1, 0.1M) was stilled at 70° C. for 2 h. The mixture was cooled to it, quenched with AcOH and diluted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography (CH2Cl2:EtOAc, 60:40, 2% AcOH) afforded the title compound as a white solid.

Workup

  1. temperatureThe mixture was cooled to it
  2. customquenched with AcOH
  3. additiondiluted with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d5efbfcb867743e58aa80a770d911435
Source dataset
uspto-grants-2007_07
Patent number
US07238706B2

Reaction notes

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