2-Chloronicotinonitrile → 2-(1-Methyl-1H-indazol-5-yloxy)-nicotinonitrile

HRID 909141

Reaktionsgleichung

Reaktionsgleichung von HRID 909141
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[CH:4]=[N:3]1.Cl[C:13]1[N:20]=[CH:19][CH:18]=[CH:17][C:14]=1[C:15]#[N:16]>CS(C)=O.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:13]3[N:20]=[CH:19][CH:18]=[CH:17][C:14]=3[C:15]#[N:16])=[CH:8][CH:9]=2)[CH:4]=[N:3]1

Komponenten

5

Edukt 2

HCID 810792-ChloronicotinonitrileHCID 441192401-Methyl-1H-indazol-5-ol

Produkt 1

HCID 574187422-(1-Methyl-1H-indazol-5-yloxy)-nicotinonitrileAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

1-Methyl-1H-indazol-5-ol (in) (synthesized as described in Example 94) (0.10 g, 0.68 mmol) and 2-chloro-nicotinonitrile (2n) (0.11 g, 0.81 mmol) were suspended in DMSO (2 mL). The reaction mixture was heated to 110° C. for 18 hours. The reaction mixture was diluted with water and extracted into EtOAc. The combined organics were dried, Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by flash column chromatography (20-100% EtOAc/Hexanes) furnished the desired product (3n), (0.152 g, 90% yield). 1H NMR (400 mHz, CD3OD) δ 8.27-8.25 (m, 1H), 8.23-8.20 (m, 1H), 8.01 (s, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.57 (d, J=2.3 Hz, 1H), 7.28-7.26 (m, 1H), 7.23-7.20 (m, 1H), 4.10 (s, 3H); MS (ESI+) m/z 251 (M+H) detected.

Aufarbeitung

  1. extractionextracted into EtOAc
  2. customThe combined organics were dried
  3. concentrationNa2SO4 and concentrated under reduced pressure
  4. customto afford the crude product
  5. customPurification by flash column chromatography (20-100% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-527f16d5580545d8a53207bffcce1909
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017641B2

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