Triphenylphosphine → 1-Methyl-4-(4-phenoxy-quinazolin-6-ylethynyl)-piperidin-4-ol

HRID 1264053Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1264053
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19]([C:21]1([OH:28])[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)#[CH:20].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].C(N(CC)CC)C>[CH3:27][N:24]1[CH2:25][CH2:26][C:21]([C:19]#[C:20][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][N:6]=[C:5]3[O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([OH:28])[CH2:22][CH2:23]1

Komponenten

6

Edukt 3

HCID 11776TriphenylphosphineHCID 14190994-Ethynyl-1-methylpiperidin-4-olHCID 113024646-Iodo4-phenoxyquinazoline

Produkt 1

HCID 186164891-Methyl-4-(4-phenoxy-quinazolin-6-ylethynyl)-piperidin-4-olAusbeute 68,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a 100 mL round bottom flask under nitrogen were added, quinazoline 13 (1.32 g, 3.80 mmol), 4-ethynyl-1-methyl-piperidin-4-ol (1.06 g, 7.6 mmol), Pd(OAc)2 (51 mg, 0.23 mmol), PPh3 (120 mg, 0.46 mmol) and triethylamine (18 mL). The flask was equipped with a reflux condenser and the mixture heated to 100° C. for 16 hours. The dark solution was then cooled and the triethylamine removed under reduced pressure. The resulting residue was diluted with EtOAc (75 mL) and H2O (25 mL) and transferred to a separatory funnel. The organic layer was washed successively with H2O (2×25 mL) and the combined aqueous washes back extracted with EtOAc (25 mL). The combined organic layers were dried (MgSO4) and the solvent removed under reduced pressure. The resulting black foam was purified on silica gel (50 g) eluting with 250 mL 30:1 CH2Cl2:MeOH, then 400 mL 30:1:1 CH2Cl2:MeOH:NEt3 to provide the desired product as a yellow foam (930 mg, 68%). 1H NMR: (CDCl3; 400 MHz) δ: 8.71 (s, 1H), 8.36 (d, 1H, J=1.9 Hz), 7.89 (d, 1H, J=8.7 Hz), 7.80 (dd, 1H, J=8.7 Hz, 1.9 Hz), 7.45 (t, 2H, J=8.3 Hz), 7.31 (m, 1H), 7.21 (m, 2H), 2.72 (br, 2H), 2.47 (br, 2H), 2.31 (s, 3H), 2.09 (m, 2H), 2.00 (m, 2H).

Aufarbeitung

  1. additionTo a 100 mL round bottom flask under nitrogen were added
  2. customThe flask was equipped with a reflux condenser
  3. temperatureThe dark solution was then cooled
  4. customthe triethylamine removed under reduced pressure
  5. additionThe resulting residue was diluted with EtOAc (75 mL) and H2O (25 mL)
  6. customtransferred to a separatory funnel
  7. washThe organic layer was washed successively with H2O (2×25 mL)
  8. extractionthe combined aqueous washes back extracted with EtOAc (25 mL)
  9. dry with materialThe combined organic layers were dried (MgSO4)
  10. customthe solvent removed under reduced pressure
  11. customThe resulting black foam was purified on silica gel (50 g)
  12. washeluting with 250 mL 30:1 CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-fe4a68dc3294455886288b07f1fcb25c
Quelldatensatz
uspto-grants-2003_04
Patentnummer
US06541481B2

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