Ethyl 2-amino-2-methylpropanoate hydrochloride → 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5,5-dimethylimidazolidine-2,4-dione

HRID 658778

Reaktionsgleichung

Reaktionsgleichung von HRID 658778
CC1C(CN2C=C(C(N=[N+]=[N-])=O)C=N2)=C(C)ON=1.[N:19]([C:22]1[CH:23]=[N:24][N:25]([CH2:27][C:28]2[C:29]([CH3:34])=[N:30][O:31][C:32]=2[CH3:33])[CH:26]=1)=[C:20]=[O:21].Cl.[NH2:36][C:37]([CH3:44])([CH3:43])[C:38](OCC)=[O:39]>C1(C)C=CC=CC=1>[CH3:34][C:29]1[C:28]([CH2:27][N:25]2[CH:26]=[C:22]([N:19]3[C:38](=[O:39])[C:37]([CH3:44])([CH3:43])[NH:36][C:20]3=[O:21])[CH:23]=[N:24]2)=[C:32]([CH3:33])[O:31][N:30]=1

Komponenten

5

Edukt 3

HCID 22343822Ethyl 2-amino-2-methylpropanoate hydrochlorideHCID 574224251-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazole-4-carbonyl azide2×HCID 584095734-((4-isocyanato-1H-pyrazol-1-yl)methyl)-3,5-dimethylisoxazole

Produkt 1

HCID 595243883-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5,5-dimethylimidazolidine-2,4-dioneAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

1-((3,5-dimethylisoxazol-4-yl) methyl)-1H-pyrazole-4-carbonyl azide (Example 10-1a) (10 g, 41.0 mmol) is stirred under nitrogen in dry toluene (150 mL) along with molecular sieves at reflux until no emission of nitrogen was observed, which indicates complete conversion of 1-((3,5-dimethylisoxazol-4-yl) methyl)-1H-pyrazole-4-carbonyl azide into 4-((4-isocyanato-1H-pyrazol-1-yl)methyl)-3,5-dimethylisoxazole. The solution was cooled down to 50° C. and ethyl 2-amino-2-methylpropanoate hydrochloride (5.30 g, 41.0 mmol) was added in one portion. Stirring continued for 3 hours at 50° C. followed by reflux for 12 hours. The mixture was filtered over a pad of celite. The filtrate was concentrated on the rotovap and the residue was purified over silica gel using 25% ethyl acetate in hexanes. Yield 65% (8.00 g), white solid. 1H NMR (DMSO-d6, 400 MHz): □s, 6H), 2.15 (s, 3H), 2.41 (s, 3H), 5.18 (s, 2H), 7.78 (d, J=0.4 Hz, 1H), 8.16 (d, J=0.4 Hz, 1H), 8.59 (br s, 1H). MS 304 (MH+). This compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 2.27 μM.

Aufarbeitung

  1. temperatureat reflux until no emission of nitrogen
  2. temperatureby reflux for 12 hours
  3. filtrationThe mixture was filtered over a pad of celite
  4. concentrationThe filtrate was concentrated on the rotovap
  5. customthe residue was purified over silica gel using 25% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-6236a0ffadf94fda8f740651fd2c1960
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08076491B2

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