5-Methylpyrazin-2-amine → (S)-2-(tert-butyldimethylsilyloxy)-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamide

HRID 1098127

Reaktionsgleichung

Reaktionsgleichung von HRID 1098127
C[Al](C)C.[CH3:5][C:6]1[N:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:20][C@@H:21]([CH2:26][O:27][CH2:28][CH3:29])[C:22](OC)=[O:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>C1(C)C=CC=CC=1.O>[Si:13]([O:20][C@@H:21]([CH2:26][O:27][CH2:28][CH3:29])[C:22]([NH:12][C:9]1[CH:8]=[N:7][C:6]([CH3:5])=[CH:11][N:10]=1)=[O:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Komponenten

7

Edukt 4

HCID 3132155-Methylpyrazin-2-amineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 57438643(S)-methyl 2-(tert-butyldimethylsilyloxy)-3-ethoxypropanoate

Produkt 1

HCID 57504608(S)-2-(tert-butyldimethylsilyloxy)-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamideAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel2×

Versuchsvorschrift

A solution of trimethylaluminium (2M in hexane, 5.51 mL, 11.02 mmol) was added dropwise to a stirred solution of 5-methylpyrazin-2-amine (CAS no. 5521-58-4) (1.20 g, 11.0 mmol) in toluene (20 mL) cooled to 0° C., over a period of 5 minutes under nitrogen. The resulting solution was stirred for 15 minutes. A solution of (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-ethoxypropanoate (Intermediate G3) (2.63 g, 10.0 mmol) in toluene (5 mL) was added dropwise over a period of 2 minutes. The resulting solution was allowed to warm to ambient temperature and then heated to reflux for 3 hours. 20% Sodium potassium tartrate solution (50 mL) then water (25 mL) were added and the mixture extracted with ethyl acetate (25 mL). The aqueous was re-extracted with ethyl acetate (25 mL). The organic phases were combined, washed with water (5 mL) and brine (20 mL), dried (MgSO4) and evaporated The residue was purified by flash silica chromatography, elution gradient 20 to 100% EtOAc in isohexane to give (2S)-2-(tert-butyl-dimethylsilyl)oxy-3-ethoxy-N-(5-methylpyrazin-2-yl)propanamide (1.45 g, 42%).

Aufarbeitung

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. extractionthe mixture extracted with ethyl acetate (25 mL)
  4. extractionThe aqueous was re-extracted with ethyl acetate (25 mL)
  5. washwashed with water (5 mL) and brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated The residue
  8. customwas purified by flash silica chromatography, elution gradient 20 to 100% EtOAc in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-c8e0a0b12a454d9daa804cc690a514a8
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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