1H-Indazole-4-boronic acid → 3-Hydroxy-6'-(1H-indazol-4-yl)-4H-1,2'-bipyridin-4-one

HRID 571059Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 571059
Br[C:2]1[N:7]=[C:6]([N:8]2[CH:13]=[CH:12][C:11](=[O:14])[C:10]([O:15]CC3C=CC(OC)=CC=3)=[CH:9]2)[CH:5]=[CH:4][CH:3]=1.[NH:25]1[C:33]2[C:28](=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=2)[CH:27]=[N:26]1>C1COCC1.C([O-])([O-])=O.[Cs+].[Cs+].[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[OH:15][C:10]1[C:11](=[O:14])[CH:12]=[CH:13][N:8]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:29]3[CH:30]=[CH:31][CH:32]=[C:33]4[C:28]=3[CH:27]=[N:26][NH:25]4)[N:7]=2)[CH:9]=1

Komponenten

6

Edukt 2

HCID 441183101H-Indazole-4-boronic acidHCID 866802746'-bromo-3-[(4-methoxybenzyl)oxy]-4H-1,2'-bipyridin-4-one

Produkt 1

HCID 674199723-Hydroxy-6'-(1H-indazol-4-yl)-4H-1,2'-bipyridin-4-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 10796Cesium carbonateLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A mixture of 6′-bromo-3-[(4-methoxybenzyl)oxy]-4H-1,2′-bipyridin-4-one (40 mg, 0.1 mmol), 1H-indazol-4-ylboronic acid (32.5 mg, 0.2 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichchloromethane complex (4 mg) in THF (2 mL) and 1 M aq. Cs2CO3 (1 mL) was heated under microwave irradiation at 160° C. for 10 min. After cooling to rt, the THF and aq. layers were separated and the aq. solution was extracted with THF (2×2 mL). The combined THF solution was treated with QuadraPure TU resin (Aldrich) for 1 h and filtered. The collected THF solution was concentrated. The concentrated residue was dissolved in TFA-DCM (1:1, 1 mL) and stirred for 1 h. The TFA-DCM solution was concentrated and the residue was purified by LCMS to give 3-Hydroxy-6′-(1H-indazol-4-yl)-4H-1,2′-bipyridin-4-one (TFA salt,). 1H NMR (499 MHz, DMSO): δ 8.60-8.55 (m, 2 H); 8.39 (d, J=2.4 Hz, 1 H); 8.18 (t, J=7.9 Hz, 1 H); 8.10 (d, J=7.7 Hz, 1 H); 7.87 (d, J=8.1 Hz, 1 H); 7.82 (d, J=7.2 Hz, 1 H); 7.70 (d, J=8.3 Hz, 1 H); 7.52 (t, J=7.7 Hz, 1 H); 6.50 (d, J=7.6 Hz, 1 H); LC/MS (M+H)+ 305; HRMS Calcd for (C17H12N4O2+H)+ 305.1033 found 305.1032.

Aufarbeitung

  1. temperatureAfter cooling to rt
  2. customthe THF and aq. layers were separated
  3. extractionthe aq. solution was extracted with THF (2×2 mL)
  4. additionThe combined THF solution was treated with QuadraPure TU resin (Aldrich) for 1 h
  5. filtrationfiltered
  6. concentrationThe collected THF solution was concentrated
  7. dissolutionThe concentrated residue was dissolved in TFA-DCM (1:1, 1 mL)
  8. concentrationThe TFA-DCM solution was concentrated
  9. customthe residue was purified by LCMS

Quellen und Nachweise

ORD-Eintrag
ord-b43db14b863043fb8aa314b52a2453ee
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09024032B2

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