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

HRID 1392722Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1392722
[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

Komponenten

7

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 86598119Dimethylformamide n-propanolLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of NAPHTHYRIDNONE 3 (1.0 eq), ester from step 1 (1.5 eq), Na2CO3 (3.5eq; 2M in H2O), Pd(OAc)2 (0.05eq.) and PPh3 (0.15eq.) 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 rt, 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.

Aufarbeitung

  1. temperatureThe mixture was cooled to rt
  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

Quellen und Nachweise

ORD-Eintrag
ord-eaaad3d4f83545049907e56012a1cf8a
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07342024B2

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