Diisopropylethylamine → 3-(tert-butyldimethylsilyloxy)-N-((5-chloro-2-methoxyphenyl)(cyano)methyl)-3-methylbutanamide

HRID 1466669Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1466669
[NH2:1][CH:2]([C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[O:12][CH3:13])[C:3]#[N:4].[C:14]([Si:18]([CH3:28])([CH3:27])[O:19][C:20]([CH3:26])([CH3:25])[CH2:21][C:22](O)=[O:23])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[Si:18]([O:19][C:20]([CH3:26])([CH3:25])[CH2:21][C:22]([NH:1][CH:2]([C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[O:12][CH3:13])[C:3]#[N:4])=[O:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:28])[CH3:27]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847023Amino-(5-chloro-2-methoxy-phenyl)-acetonitrileHCID 866418543-(tert-Butyldimethylsilyloxy)-3-methylbutyric acid

Produkt 1

HCID 668471763-(tert-butyldimethylsilyloxy)-N-((5-chloro-2-methoxyphenyl)(cyano)methyl)-3-methylbutanamideAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-amino-2-(5-chloro-2-methoxyphenyl)acetonitrile (500 mg, 2.54 mmol) in DMF (2 mL) was added to a solution of 3-(tert-butyl-dimethyl-silanyloxy)-3-methyl-butyric acid (prepared according to patent EP2025667) (590 mg, 2.54 mmol), diisopropylethylamine (0.87 mL, 5.08 mmol) and HATU (966 mg, 2.54 mmol) in DMF (5 mL) and stirred for 18 hours. Ethyl acetate was added, the organics washed with sodium hydrogen carbonate (sat. aq.) and brine, then evaporated to dryness. The residues were purified by flash chromatography on silica gel (0 to 5% ethyl acetate in dichloromethane) to yield 740 mg (73%) of 3-(tert-butyldimethylsilyloxy)-N-((5-chloro-2-methoxyphenyl)(cyano)methyl)-3-methylbutanamide. LCMS (ESI) m+H=411.4.

Aufarbeitung

  1. washthe organics washed with sodium hydrogen carbonate (sat. aq.) and brine
  2. customevaporated to dryness
  3. customThe residues were purified by flash chromatography on silica gel (0 to 5% ethyl acetate in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-ef0bf94875b54c73a42470b5a131940d
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US08999998B2

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