Methanol → HCID 178473712, Verbindung

HRID 628951Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 628951
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]#[CH:15])=[CH:11][CH:12]=2)[C@H:7]([NH:16][C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][N:18]=2)[CH2:6][C@@H:5]1[CH3:25])(=[O:3])[CH3:2].CO.[N:28]([Si](C)(C)C)=[N+:29]=[N-:30]>[Cu]I.CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:28]=[N:29][NH:30][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:16][C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][N:18]=2)[CH2:6][C@@H:5]1[CH3:25])(=[O:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 887MethanolHCID 78378Azidotrimethylsilane3×HCID 867120316-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Produkt 1

HCID 178473712HCID 178473712, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator2×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A microwaveable vial was charged with 6-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 9) (527 mg, 1.595 mmol), Copper (I) Iodide (30 mg, 0.158 mmol), methanol (0.333 ml), DMF (3 ml). Azidotrimethylsilane (0.423 ml, 3.19 mmol) was added to the solution, the vial sealed and heated at 100° C. for 1 h (microwave). Azidotrimethylsilane (0.211 ml, 1.59 mmol) was added to the vial and the mixture heated for a further 1 h (sealed vial, microwave). Azidotrimethylsilane (0.211 ml, 1.590 mmol), and copper (I) iodide (30 mg, 0.158 mmol) was added. The vial was resealed and heated for a further 1 h. The reaction solution was concentrated in vacuo, diluted with water (15 ml) and extracted with DCM (3×10 ml). The organics were combined and dried (hydrophobic frit). The mixture was concentrated and the sample purified by chromatography on a silica cartridge (50 g) eluting with a methanol/DCM gradient (0-10%). The appropriate fractions were combined and the solvent evaporated in vacuo to give 6-(((2S,4R)-1-acetyl-2-methyl-6-(1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (50 mg). LCMS (formate): Rt 0.71 min, MH+ 374

Aufarbeitung

  1. customthe vial sealed
  2. temperatureheated for a further 1 h
  3. custom(sealed vial, microwave)
  4. temperatureheated for a further 1 h
  5. concentrationThe reaction solution was concentrated in vacuo
  6. additiondiluted with water (15 ml)
  7. extractionextracted with DCM (3×10 ml)
  8. customdried (hydrophobic frit)
  9. concentrationThe mixture was concentrated
  10. customthe sample purified by chromatography on a silica cartridge (50 g)
  11. washeluting with a methanol/DCM gradient (0-10%)
  12. customthe solvent evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d30b042c177e4037915d8d8ae367f4c9
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315487B2

Notizen zur Reaktion

Wird geladen…