Sodium Carbonate → ethyl 1-({3'-[3-[(cyclopropylamino)carbonyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]biphenyl-4-yl}methyl)cyclobutanecarboxylate

HRID 1294393Notes

Reaction equation

HRID 1294393 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[C:16](=[O:17])[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]([C:18]3[CH:19]=[C:20]([C:24]4[CH:29]=[CH:28][C:27](C(O)=O)=[CH:26][CH:25]=4)[CH:21]=[CH:22][CH:23]=3)[CH:8]=2)=[O:6])[CH2:3][CH2:2]1.BrC1C=CC([CH2:38][C:39]2([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:42][CH2:41][CH2:40]2)=CC=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(O)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:1]1([NH:4][C:5]([C:7]2[C:16](=[O:17])[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]([C:18]3[CH:19]=[C:20]([C:24]4[CH:25]=[CH:26][C:27]([CH2:38][C:39]5([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:42][CH2:41][CH2:40]5)=[CH:28][CH:29]=4)[CH:21]=[CH:22][CH:23]=3)[CH:8]=2)=[O:6])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 100254323'-[3-[(Cyclopropylamino)carbonyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]-1,1'-biphenyl-4-carboxylic AcidHCID 69158278Ethyl 1-(4-bromobenzyl)cyclobutanecarboxylate

Product 1

HCID 69158192ethyl 1-({3'-[3-[(cyclopropylamino)carbonyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]biphenyl-4-yl}methyl)cyclobutanecarboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86598119Dimethylformamide n-propanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of NAPHTHYRIDINONE 3 (1.0 eq), ester from step 1 (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 stirred 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/MeOH, 99:1) afforded the title compound.

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-335c7ea1e00e44798eb9fb00402823f2
Source dataset
uspto-grants-2007_07
Patent number
US07238706B2

Reaction notes

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