Benzo(B)Thiophene-2-Boronic Acid → HCID 25019426, Verbindung

HRID 1878739Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1878739
O.C(=O)([O-])[O-].[Na+].[Na+].Cl[C:9]1[CH:10]=[CH:11][C:12](=[O:30])[N:13]([CH2:15][CH2:16][O:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=2)[N:14]=1.[S:31]1[C:35](B(O)O)=[CH:34][C:33]2[CH:39]=[CH:40][CH:41]=[CH:42][C:32]1=2>COCCOC.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].C(Cl)Cl>[S:31]1[C:35]([C:9]2[CH:10]=[CH:11][C:12](=[O:30])[N:13]([CH2:15][CH2:16][O:17][C:18]3[C:27]4[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=4)[N:21]=[CH:20][CH:19]=3)[N:14]=2)=[CH:34][C:33]2[CH:39]=[CH:40][CH:41]=[CH:42][C:32]1=2

Komponenten

7

Edukt 3

HCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 2735133Sodium Carbonate MonohydrateHCID 598430126-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

Produkt 1

HCID 25019426HCID 25019426, VerbindungAusbeute 56,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of sodium carbonate hydrate (250 mg, 2016 μmol), PdCl2(dppf)-CH2Cl2 adduct (30 mg, 37 μmol), 6-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2 H)-one (220 mg, 663 μmol), and benzo[b]thiophen-2-ylboronic acid (290 mg, 1629 μmol) in DME (5 mL) and H2O (2 mL) was heated to 80° C. under nitrogen for 18 h. The mixture was cooled to room temperature and partitioned between EtOAc (50 mL) and H2O (20 mL). The organic phase was washed with H2O (2×), NH4Cl (aq), dried over Na2SO4, and concentrated to a brown solid. The solid was triturated with hot hexane-EtOAc-MeOH (2:1:0.1) twice and the solid was further washed with MeOH in EtOAc (1%), CH2Cl2 (de-colorization), and ether to give the product as an off-white solid (160 mg). MS (ESI pos. ion) calc'd for C24H19N3O3S: 429.11; found 430.2 (MH+). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.65 (s, 3 H) 5.46 (s, 4 H) 7.76 (d, J=4.11 Hz, 1 H) 7.81 (d, J=9.19 Hz, 1 H) 7.95 (d, J=9.39 Hz, 1 H) 8.08 (s, 1 H) 8.24 (d, J=3.33 Hz, 2 H) 8.67 (d, J=5.09 Hz, 1 H) 8.81 (d, J=8.41 Hz, 2 H) 8.88 (s, 1 H) 9.00 (d, J=9.78 Hz, 1 H) 9.44 (d, J=4.30 Hz, 1 H)

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between EtOAc (50 mL) and H2O (20 mL)
  3. washThe organic phase was washed with H2O (2×), NH4Cl (aq)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to a brown solid
  6. customThe solid was triturated with hot hexane-EtOAc-MeOH (2:1:0.1) twice
  7. washthe solid was further washed with MeOH in EtOAc (1%), CH2Cl2 (de-colorization), and ether

Quellen und Nachweise

ORD-Eintrag
ord-13c6c1a7004248149737dc973947038b
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08314087B2

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