Cesium carbonate → Ethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047112Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1047112
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:5]2=[O:19].[CH2:20]([NH:22][C:23](=[O:43])[NH:24][C:25]1[N:30]=[CH:29][C:28](B(O)O)=[C:27]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:26]=1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:12]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([C:28]3[CH:29]=[N:30][C:25]([NH:24][C:23](=[O:43])[NH:22][CH2:20][CH3:21])=[CH:26][C:27]=3[C:34]3[S:35][CH:36]=[C:37]([C:39]([F:42])([F:40])[F:41])[N:38]=3)=[CH:11][N:10]=2)[C:5](=[O:19])[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:7]1)[CH3:13]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2×HCID 68748009Ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2×

Produkt 1

HCID 68747705Ethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylateAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

In a round bottomed flask, ethyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 15, 400 mg, 1.3 mmol), 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 700 mg, 1.72 mmol) and cesium carbonate (3.78 g, 2.46 mmol) were combined and suspended in 10 mL of dioxane:water (8:2). The suspension was purged with argon for 15 min. then tetrakis (triphenylphosphine) palladium (140 mg, 0.2 mmol) was added under argon atmosphere and the reaction mixture was heated to 80-90° C. for 5 h. After completion of the reaction, the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure to a residue, to which acetonitrile was added. The precipitated solid was filtered and dried to afford 150 mg (25%) of ethyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.

Aufarbeitung

  1. customThe suspension was purged with argon for 15 min.
  2. customAfter completion of the reaction
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationfiltered through celite
  5. concentrationThe filtrate was concentrated under reduced pressure to a residue, to which acetonitrile
  6. additionwas added
  7. filtrationThe precipitated solid was filtered
  8. customdried

Quellen und Nachweise

ORD-Eintrag
ord-b37a76790c104171ba89297c5c90c0b9
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569484B2

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