Dichloromethane → 4-amino-8-(2,4-dimethoxypyrimidin-5-yl)-N-ethylcinnoline-3-carboxamide

HRID 2375672

Reaktionsgleichung

Reaktionsgleichung von HRID 2375672
[NH2:1][C:2]1[C:11]2[C:6](=[C:7](Br)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH3:17])=[O:14].[CH3:18][O:19][C:20]1[N:25]=[C:24]([O:26][CH3:27])[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21]=1.ClCCl>C(OCC)(=O)C>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:23]3[C:24]([O:26][CH3:27])=[N:25][C:20]([O:19][CH3:18])=[N:21][CH:22]=3)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH3:17])=[O:14]

Komponenten

5

Edukt 3

HCID 6344DichloromethaneHCID 162183882,4-Dimethoxypyrimidine-5-boronic acid pinacol ester3×HCID 672286714-Amino-8-bromo-N-ethyl-cinnoline-3-carboxamide

Produkt 1

HCID 251334424-amino-8-(2,4-dimethoxypyrimidin-5-yl)-N-ethylcinnoline-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

The title compound was prepared from 4-amino-8-bromo-N-ethyl-cinnoline-3-carboxamide (200.0 mg, 0.678 mmol) and 2,4-dimethoxyprimidine-5-boronic acid pinacol ester (363.1 mg, 1.362 mmol) according to Method B except that the reaction was heated at 90° C. to fully dissolve the starting materials. After 4 hours, additional 2,4-dimethoxyprimidine-5-boronic acid pinacol ester (363.1 mg, 1.362 mmol) was added and the reaction was refluxed overnignt. A third addition of 2,4-dimethoxyprimidine-5-boronic acid pinacol ester (363.1 mg, 1.362 mmol) and an additional 5 mol % tetrakis(triphenylphospine)palladium(0) were required to force the reaction to completion. The reaction was then worked up as described in Method B using dichloromethane rather than ethyl acetate for the extraction and crystallizing the material obtained from the flash column from chloroform/hexanes to afford the title compound as a white solid (89.5 mg, 37%). 1H NMR (300.132 MHz, CDCl3) δ 8.47 (s, 1H), 8.32 (s, 1H), 7.90 (dd, J=7.6, 2.1 Hz, 1H), 7.78-7.70 (m, 2H), 4.07 (s, 3H), 3.93 (s, 3H), 3.53 (dq, J=5.7, 7.3 Hz, 2H), 1.28 (t, J=7.3 Hz, 3H). MS APCI, m/z=354 (M+H). HPLC 2.07 min.

Aufarbeitung

  1. dissolutionto fully dissolve the starting materials
  2. temperaturethe reaction was refluxed overnignt
  3. customthe reaction to completion
  4. extractionfor the extraction
  5. customcrystallizing the material

Quellen und Nachweise

ORD-Eintrag
ord-f640dd042e704a8d9faade1ec2e1bb8d
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07465795B2

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