Sodium hydride → HCID 178509490, Verbindung

HRID 1398490Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398490
Cl[CH:2]1[NH:7][C:6]([NH2:8])=[N:5][CH:4]=[C:3]1[N+:9]([O-:11])=[O:10].[H-].[Na+].[NH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:23]#[N:24])[CH:21]=2)[CH:16]=[N:15]1>CN(C=O)C>[NH2:8][C:6]1[NH:7][CH:2]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]#[N:24])[CH:21]=3)[CH:16]=[N:15]2)[C:3]([N+:9]([O-:11])=[O:10])=[CH:4][N:5]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 4225291H-indazole-6-carbonitrileHCID 178508523HCID 178508523, Verbindung

Produkt 1

HCID 178509490HCID 178509490, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 6-chloro-5-nitro-1,6-dihydropyrimidin-2-amine (538.5 mg, 60% purity, 2.00 mmol) in DMF (10 mL) was added NaH (60% oil suspension, 172 mg, 4.30 mmol) at 0° C. Mixture was stirred at RT for 10 min before addition of 1H-indazole-6-carbonitrile (410 mg, 2.87 mmol). Stirring was continued at RT for 18 hr. The reaction mixture was quenched with water (25 mL) cooled in an ice bath and extracted with EtOAc (3×20 mL). Insoluble solid formed during extraction was separated out. Combined EtOAc extract was washed with water (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. A portion (70 mg) of the crude product was purified by reverse phase preparative HPLC to give the title compound: 1H NMR (250 MHz, DMSO) δ 7.79 (1 H, dd, J=8.22, 1.07 Hz), 8.14 (1H, d, J=8.22 Hz), 8.20 (1H, br. s.), 8.33 (1H, br. s.), 8.65 (1H, s), 8.91 (1H, s), 9.03 (1H, s); LC-MS: m/z=+281.95 (M+H)+.

Aufarbeitung

  1. customThe reaction mixture was quenched with water (25 mL)
  2. temperaturecooled in an ice bath
  3. extractionextracted with EtOAc (3×20 mL)
  4. customInsoluble solid formed during extraction
  5. customwas separated out
  6. extractionCombined EtOAc extract
  7. washwas washed with water (20 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customA portion (70 mg) of the crude product was purified by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-95557195f6cf49499890de38052fe0aa
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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