2,8-Dichloro-quinoline-3-carbaldehyde → (8-Chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamine

HRID 216776Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 216776
BrC1C=CC=[C:6]2[C:11]=1[N:10]=[C:9](C1C=CC=C(F)C=1)[C:8](CN1C(=O)C3C(=CC=CC=3)C1=O)=[CH:7]2.ClC1C(C=O)=CC2C(=C(Cl)C=CC=2)N=1.[Cl:45][C:46]1[C:55]([CH2:56][N:57]2[C:65](=[O:66])[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[C:58]2=[O:67])=[CH:54][C:53]2[C:48](=[C:49]([Cl:68])[CH:50]=[CH:51][CH:52]=2)[N:47]=1.[Br-].N1C=CC=CC=1[Zn+]>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:45][C:46]1[C:55]([CH2:56][N:57]2[C:65](=[O:66])[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[C:58]2=[O:67])=[CH:54][C:53]2[C:48](=[C:49]([Cl:68])[CH:50]=[CH:51][CH:52]=2)[N:47]=1.[Cl:68][C:49]1[CH:50]=[CH:51][CH:52]=[C:53]2[C:48]=1[N:47]=[C:46]([C:9]1[CH:8]=[CH:7][CH:6]=[CH:11][N:10]=1)[C:55]([CH2:56][NH2:57])=[CH:54]2

Komponenten

8

Edukt 4

HCID 149171252,8-Dichloro-quinoline-3-carbaldehydeHCID 577078392-((8-Bromo-2-(3-fluorophenyl)quinolin-3-yl)methyl)isoindoline-1,3-dioneHCID 577080182-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dioneHCID 178418723HCID 178418723, Verbindung

Produkt 2

HCID 57707932(8-Chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamineHCID 577080182-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

2-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione was prepared in the similar manner as 2-((8-bromo-2-(3-fluorophenyl)quinolin-3-yl)methyl)-isoindoline-1,3-dione from 2,8-dichloroquinoline-3-carbaldehyde. A mixture of 2-((2,8-dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione (71 mg, 0.2 mmol), 2-pyridylzinc bromide (0.5 M, 0.8 mL, 2.0 eq) and tetrakis(triphenylphosphine) palladium (11 mg, 5%) in dioxane (3 mL) was purged with N2 and heated to 65° C. After 12 h, the reaction was cooled to rt and quenched with NH4Cl solution. After work up, The residue containing a mixture of 2-((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)isoindoline-1,3-dione and 2-(((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)carbamoyl)benzoic acid was treated with NH2NH2 (31 μL) in EtOH (1 mL) at reflux. After usual work up, the residue was purified on column chromatography on silica gel (DCM/MeOH/Et3N, 20/1/0.1) to give a pale yellow solid as (8-chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (d, J=8.0 Hz, 1H), 8.31 (d, J=8.0 Hz, 1H), 8.17 (s, 1H), 7.84 (t, J=8.0 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.38 (t, J=8.0 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 4.13 (s, 3H). Mass Spectrum (ESI) m/e=270 (M+1).

Aufarbeitung

  1. customwas purged with N2
  2. temperaturethe reaction was cooled to rt
  3. customquenched with NH4Cl solution
  4. additionAfter work up, The residue containing
  5. additiona mixture of 2-((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)isoindoline-1,3-dione and 2-(((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)carbamoyl)benzoic acid
  6. additionwas treated with NH2NH2 (31 μL) in EtOH (1 mL)
  7. temperatureat reflux
  8. customAfter usual work up, the residue was purified on column chromatography on silica gel (DCM/MeOH/Et3N, 20/1/0.1)

Quellen und Nachweise

ORD-Eintrag
ord-1ad8516615154a1e9fa7cd6b294e00f8
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193199B2

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