(Bromoethynyl)benzene → (4-Methyl-pyridin-2-yl)-[6-(2-phenylethynyl-oxazol-5-yl)-pyridin-2-yl]-amine

HRID 1854617Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854617
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[O:19][CH:18]=[N:17][CH:16]=3)[N:10]=2)[CH:3]=1.Br[C:21]#[C:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC(P(C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1.O(C(C)(C)C)[Li]>O1CCOCC1.C1CC=CCCC=C1.C1CC=CCCC=C1.[Ni].O>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[O:19][C:18]([C:21]#[C:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:17][CH:16]=3)[N:10]=2)[CH:3]=1

Komponenten

8

Edukt 4

HCID 136737(Bromoethynyl)benzene2×HCID 4983791,2-Bis(diphenylphosphino)benzene2×HCID 53311228(4-Methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amineHCID 178506942HCID 178506942, Verbindung

Produkt 1

HCID 53312247(4-Methyl-pyridin-2-yl)-[6-(2-phenylethynyl-oxazol-5-yl)-pyridin-2-yl]-amineAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6433264Bis(1,5-cyclooctadiene)nickelKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A sealed tube with a teflon screw cap was charged with a mixture of (4-methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amine (200 mg, 0.793 mmol), bromoethynylbenzene (172 mg, 0.951 mmol) Ni(cod)2 (11 mg, 0.040 mmol), dppbz (18 mg, 0.040 mmol) and LiOtBu (127 mg, 1.59 mmol) in dry dioxane (5 ml) and heated to 100° C. for 2 h. Further bromoethynylbenzene (172 mg), Ni(cod)2 (11 mg), dppbz (18 mg) LiOtBu (127 mg, 1.59 mmol) and dry dioxane (2 ml) were added and heating continued for 36 h. The cooled mixture was treated with water and extracted with DCM. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane to afford the title compound as an off-white solid (35 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 8.11 (d, J=5.1 Hz, 1H), 7.87 (s, J=26.8 Hz, 1H), 7.80-7.69 (m, 5H), 7.60-7.49 (m, 3H), 7.33 (d, J=7.2 Hz, 1H), 6.77 (d, J=5.1 Hz, 1H), 2.33 (s, 3H). (ESI+) m/z 353 (M+H)+. Retention time=3.24 mins (method 1).

Aufarbeitung

  1. temperatureheating
  2. extractionextracted with DCM
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane

Quellen und Nachweise

ORD-Eintrag
ord-cec2e910d1064555adeea3f514b21649
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962665B2

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