Cesium fluoride → 3-(6-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl)thiophene-2-carbonitrile

HRID 445221Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 445221
Br[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]#[N:8].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].Cl.[OH:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([O:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]3)=[CH:45][CH:44]=1)=[C:37](B(O)O)[CH:36]=[CH:35]2>C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[OH:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([O:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH2:50][CH2:51][N:52]3[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]3)=[CH:45][CH:44]=1)=[C:37]([C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]#[N:8])[CH:36]=[CH:35]2

Komponenten

8

Edukt 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 27400883-Bromothiophene-2-carbonitrileHCID 673086676-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ylboronic acid hydrochloride

Produkt 1

HCID 583385773-(6-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl)thiophene-2-carbonitrileAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 702EthanolLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Add 3-bromothiophene-2-carbonitrile (93 mg, 494.6 μmol), palladium (II) acetate (12 mg, 53.4 μmol), tricyclohexylphosphine (21 mg, 74.9 μmol), cesium fluoride (336 mg, 2.2 mmol) to a solution of 6-hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ylboronic acid hydrochloride (100 mg, 245.5 μmol) in ethanol (2 mL), and acetonitrile (8 mL). Purge the reaction vessel 3 times with nitrogen. Stir the mixture at 85° C. for 2 hours. Cool the mixture and filter. Wash the resulting solids with acetonitrile. Concentrate the combined filtrate and washes. Purify the residue by DOWEX ion exchange resin to obtain the crude product. Purify the crude product by Prep-HPLC to obtain the title compound (12 mg, 24.55 μmol).

Aufarbeitung

  1. customPurge the reaction vessel 3 times with nitrogen
  2. temperatureCool the mixture
  3. filtrationfilter
  4. washWash the resulting solids with acetonitrile
  5. concentrationConcentrate the combined filtrate and washes
  6. customPurify the residue by DOWEX ion exchange resin
  7. customto obtain the crude product
  8. customPurify the crude product by Prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-7bc79f7573b442bc96ef541f241ff276
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476300B2

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