Potassium Carbonate → 2-[5-(4,5-Dihydro[1,2,4]triazolo[4,3-a]quinolin-7-yl)pyridin-3-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol

HRID 1521591Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1521591
[F:1][C:2]([F:19])([F:18])[C:3]([C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[N:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].Br[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]1[CH:31]=[N:32][N:33]=[C:26]1[CH2:25][CH2:24]2.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)(C)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH:31]1[N:27]2[C:28]3[C:23]([CH2:24][CH2:25][C:26]2=[N:33][N:32]=1)=[CH:22][C:21]([C:11]1[CH:10]=[C:9]([C:3]([OH:8])([C:4]([F:7])([F:6])[F:5])[C:2]([F:19])([F:18])[F:1])[CH:14]=[N:13][CH:12]=1)=[CH:30][CH:29]=3

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 21543699HCID 21543699, VerbindungHCID 89961718(5-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)pyridin-3-yl)boronic acid

Produkt 1

HCID 899615962-[5-(4,5-Dihydro[1,2,4]triazolo[4,3-a]quinolin-7-yl)pyridin-3-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 962WaterLösungsmittelHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A vial containing the title compound from Example 61 Step B (15 mg, 0.05 mmol), the title compound from Example 22 Step B (11.7 mg, 0.047 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.68 mg, 5.19 μmol) and potassium carbonate (21.5 mg, 0.156 mmol) in tert-butanol (577 μL) and water (72 μL) was flushed with nitrogen, sealed tightly and heated to 80° C. overnight. The reaction solution was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with acetonitrile and purified by HPLC (C18 column, 10 to 100% acetonitrile/water, both 0.1% v/v trifluoroacetic acid). Fractions containing product were combined, aqueous 1 M hydrochloric acid solution was added and the solution concentrated under reduced pressure to provide the title compound: LCMS m/z 414.79 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 9.38 (s, 1H), 9.11 (s, 1H), 8.85 (s, 1H), 8.27 (s, 1H), 7.92 (d, J=8.34 Hz, 1H) 7.87 (d, J=1.71 Hz, 1H), 7.81 (dd, J=1.94, 8.34 Hz, 1H), 3.15 (s, 4H).

Aufarbeitung

  1. customsealed tightly
  2. temperatureThe reaction solution was then cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting residue was diluted with acetonitrile
  5. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water
  6. additionFractions containing product
  7. additionaqueous 1 M hydrochloric acid solution was added
  8. concentrationthe solution concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-1a4d51e581f944aa864ef31b0d3c155c
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073929B2

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