Water → 2-{[4-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-6-ethylpyridin-2-yl]amino}-1,3-thiazole-5-carbonitrile

HRID 1814011Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1814011
[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([CH2:16][CH3:17])[N:13]=[C:12]([NH2:18])[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[C:20]1[S:21][C:22]([C:25]#[N:26])=[CH:23][N:24]=1.[H-].[Na+].O>C1COCC1>[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([CH2:16][CH3:17])[N:13]=[C:12]([NH:18][C:20]2[S:21][C:22]([C:25]#[N:26])=[CH:23][N:24]=2)[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydride3×HCID 14852222-Chlorothiazole-5-carbonitrile3×HCID 695514044-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-6-ethylpyridin-2-amine

Produkt 1

HCID 865882682-{[4-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-6-ethylpyridin-2-yl]amino}-1,3-thiazole-5-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

4-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-6-ethylpyridin-2-amine 12-1 (0.159 g, 0.60 mmol) was dissolved in 2 mL THF. 2-Chloro-1,3-thiazole-5-carbonitrile (0.103 g, 0.72 mmol) and sodium hydride (60% dispersion in mineral oil) (0.057 g, 2.38 mmol) were added and the solution was heated to 75° C. After 4 hours more 2-chloro-1,3-thiazole-5-carbonitrile (0.043 g, 0.30 mmol) and sodium hydride (0.014 g, 0.60 mmol) were added. After 5.5 hours more 2-chloro-1,3-thiazole-5-carbonitrile (0.086 g, 0.60 mmol) and sodium hydride (0.029 g, 1.19 mmol) were added. After 8.5 hours the solution was allowed to cool to room temperature. H2O was added and the reaction was concentrated in vacuo (to remove THF). 1N HCl was added to adjust to neutral pH. The resulting precipitate was filtered and washed with water to afford the desired compound 12-2 as a yellow solid. 1H NMR (DMSO-d6) δ 12.23 (s, 1H), 8.25 (s, 1H), 6.70 (s, 1H), 6.83 (s, 1H), 4.73 (bs, 2H), 2.79 (q, 2H, J=7.63 Hz), 1.32 (t, 3H, J=7.63 Hz), 0.94 (s, 9H), 0.10 (s, 6H).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. concentrationthe reaction was concentrated in vacuo (to remove THF)
  3. addition1N HCl was added
  4. filtrationThe resulting precipitate was filtered
  5. washwashed with water

Quellen und Nachweise

ORD-Eintrag
ord-9811d23072164c63880ddd10cac442eb
Quelldatensatz
uspto-grants-2005_04
Patentnummer
US06875767B2

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