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Morpholine → 2-(3-methoxyphenyl)-9-morpholino-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

HRID 532911
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 532911
I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][N:14]=[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[CH:12]=[C:7]12.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][O:24][C:20]1[CH:19]=[C:18]([C:13]2[CH:12]=[C:7]3[C:8]4[C:3]([CH2:4][CH2:5][N:6]3[C:16](=[O:17])[CH2:15][N:14]=2)=[C:2]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:11]=[CH:10][CH:9]=4)[CH:23]=[CH:22][CH:21]=1
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Komponenten

7

Edukt 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 867113559-iodo-2-(3-methoxyphenyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

Produkt 1

HCID 733353432-(3-methoxyphenyl)-9-morpholino-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-oneAusbeute 60,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845
palladium(II) acetate
Katalysator
HCID 634876Binap, (A+-)-Katalysator
HCID 1140TolueneLösungsmittel2×

Versuchsvorschrift

A solution of Pd(OAc)2 (4.0 mg, 0.017 mmol), and BINAP (10.5 mg, 0.017 mmol) in toluene (5 mL) was stirred at RT under N2 for 10 min, and then transferred to a mixture of 9-iodo-2-(3-methoxyphenyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (Example 30) (150 mg, 0.34 mmol), morpholine (35 μL, 0.41 mmol) and Cs2CO3 (550 mg, 1.69 mmol) in toluene (5 mL). The reaction was stirred at RT under N2 for 5 min, and then heated to reflux for 24 h. The mixture was allowed to cool to RT, and then filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, hexane to hexane/AcOEt 1:1) and the brown solid obtained was recrystallized from hexane to give the title compound (83 mg) as a beige solid. UPLC-MS: MS 404.5 (M+H+); UPLC rt 1.09 min. 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 2.84-3.03 (m, 6 H); 3.76-3.95 (m, 6 H); 3.87 (s, 3H); 4.51 (br. s., 2 H); 6.92 (s, 1 H); 7.00 (dd, J=8.21, 2.74 Hz, 1 H); 7.14 (d, J=7.82 Hz, 1 H); 7.28-7.51 (m, 5 H).

Aufarbeitung

  1. temperatureheated
  2. temperatureto reflux for 24 h
  3. temperatureto cool to RT
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (SiO2, hexane to hexane/AcOEt 1:1)
  7. customthe brown solid obtained
  8. customwas recrystallized from hexane

Quellen und Nachweise

ORD-Eintrag
ord-498e9257f5f94c8db5f3e78085a824b2
Quelldatensatz
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08853203B2

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