Potassium Carbonate → HCID 71604910, Verbindung

HRID 632618Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 632618
[F:1][C:2]1([F:46])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C@@H:16]([OH:18])[CH2:15][C:14]([CH3:20])([CH3:19])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30]([OH:33])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:34]([F:45])[C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH2:4][CH2:3]1.C1(C)C=CC(S(O[CH2:57][CH2:58][CH2:59][S:60]([CH3:63])(=[O:62])=[O:61])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].ClC1N=CC(O)=CN=1>CN(C)C=O.O>[F:46][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[C@@H:16]([OH:18])[CH2:15][C:14]([CH3:19])([CH3:20])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:22][CH2:23][N:24]([C:27]4[N:32]=[CH:31][C:30]([O:33][CH2:57][CH2:58][CH2:59][S:60]([CH3:63])(=[O:62])=[O:61])=[CH:29][N:28]=4)[CH2:25][CH2:26]3)[C:9]=2[C@@H:34]([F:45])[C:35]2[CH:36]=[CH:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=2)[CH2:6][CH2:7]1

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 145957002-Chloro-5-pyrimidinolHCID 22732325(3-(Methylsulfonyl)propyl 4-methylbenzenesulfonateHCID 56598385(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

Produkt 1

HCID 71604910HCID 71604910, VerbindungAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 145 mg (0.224 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol, which was prepared by a method similar to that of Reference Example 23, in 0.7 ml of N,N-dimethylformamide, 130 mg (0.445 mmol) of 3-(methylsulfonyl)propyl p-toluenesulfonate and 135 mg (0.977 mmol) of potassium carbonate were added, and the mixture was stirred at 80° C. for 4 hours. 44 mg (0.337 mmol) of 2-chloro-5-hydroxypyrimidine was further added thereto, and the mixture was stirred at 80° C. for 3 hours. After completion of the reaction, the reaction solution was poured into water and extracted with toluene twice. The obtained organic phases were combined and washed with saturated sodium chloride aqueous solution, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=55/45-25/75 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 137.0 mg of the title compound as a white solid (yield: 80%).

Aufarbeitung

  1. stirringthe mixture was stirred at 80° C. for 3 hours
  2. customAfter completion of the reaction
  3. extractionextracted with toluene twice
  4. washwashed with saturated sodium chloride aqueous solution
  5. distillationthe solvent was distilled off under reduced pressure
  6. concentrationwas concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-e441b525801345b69fd75df2a1ad9945
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321747B2

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