Dimethylformamide → (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxy-4-methylpentan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 2061841Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2061841
CN(C)[CH:3]=[C:4]([C:10](=[O:39])[C:11]1[CH:16]=[C:15]([C:17]2[CH:18]=[N:19][C:20]([NH:32][C:33]([NH:35][CH2:36][CH3:37])=[O:34])=[CH:21][C:22]=2[C:23]2[S:24][CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[N:27]=2)[CH:14]=[CH:13][C:12]=1F)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[NH2:41][C@@H:42]([CH2:45][CH:46]([CH3:48])[CH3:47])[CH2:43][OH:44].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>C1COCC1>[CH2:36]([NH:35][C:33](=[O:34])[NH:32][C:20]1[N:19]=[CH:18][C:17]([C:15]2[CH:16]=[C:11]3[C:12](=[CH:13][CH:14]=2)[N:41]([C@@H:42]([CH2:45][CH:46]([CH3:48])[CH3:47])[CH2:43][OH:44])[CH:3]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:10]3=[O:39])=[C:22]([C:23]2[S:24][CH:25]=[C:26]([C:28]([F:29])([F:31])[F:30])[N:27]=2)[CH:21]=1)[CH3:37]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 111307L-LeucinolHCID 67028768Ethyl 3-(dimethylamino)-2-(5-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-2-fluorobenzoyl)acrylate2×

Produkt 1

HCID 59415791(S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxy-4-methylpentan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylateAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

Ethyl 3-(dimethylamino)-2-(5-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-2-fluorobenzoyl)acrylate (0.150 g, 0.26 mmol, Intermediate 125) and (S)-2-amino-4-methylpentan-1-ol (0.033 ml, 0.26 mmol) were taken up in THF (2 ml). The mixture was placed in an oil bath and heated to 60° C. for 2 h. Potassium carbonate (0.107 g, 0.78 mmol) was added followed by DMF (1 ml) and the mixture was stirred at 60° C. overnight. Reaction was cooled to room temperature and concentrated in vacuo. The residue was then diluted with water (0.5 mL) and cooled to 0° C. 1N HCl was added drop wise until pH˜4. A light yellow solid was collected by filtration, washed with water, and dried in vacuum oven overnight at 50° C. to give (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxy-4-methylpentan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (0.072 g, 44%) as a yellow solid.

Aufarbeitung

  1. customThe mixture was placed in an oil bath
  2. customReaction
  3. temperaturewas cooled to room temperature
  4. concentrationconcentrated in vacuo
  5. additionThe residue was then diluted with water (0.5 mL)
  6. temperaturecooled to 0° C
  7. addition1N HCl was added drop wise until pH˜4
  8. filtrationA light yellow solid was collected by filtration
  9. washwashed with water
  10. customdried in vacuum oven overnight at 50° C.

Quellen und Nachweise

ORD-Eintrag
ord-af6744ecf10849c29edcbd9c8fc3dd2e
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08283361B2

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