Cesium carbonate → 6-chloro-7-methoxy-2,3-dimethyl-4-(3,3,7-trimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)quinoline

HRID 1618614Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1618614
[CH3:1][C:2]1([CH3:18])[C:10]2[C:5](=[C:6]([CH3:17])[C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[NH:4][CH2:3]1.Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:31][CH3:32])=[C:27]([Cl:30])[CH:28]=2)[N:23]=[C:22]([CH3:33])[C:21]=1[CH3:34].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C(Cl)Cl.CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:30][C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][C:26]=1[O:31][CH3:32])[N:23]=[C:22]([CH3:33])[C:21]([CH3:34])=[C:20]2[N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:6]=2[CH3:17])[C:2]([CH3:18])([CH3:1])[CH2:3]1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 672846634-(3,3,7-Trimethylindolin-6-yl)morpholineHCID 672854564,6-Dichloro-7-methoxy-2,3-dimethylquinoline

Produkt 1

HCID 509399946-chloro-7-methoxy-2,3-dimethyl-4-(3,3,7-trimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)quinoline

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-(3,3,7-trimethylindolin-6-yl)morpholine (37.9 mg, 0.154 mmol), 4,6-dichloro-7-methoxy-2,3-dimethylquinoline (made by procedures A-D, 59.1 mg, 0.231 mmol), cesium carbonate (75.3 mg, 0.231 mmol), Pd2(dba)3 (28.4 mg, 0.031 mmol), and Xantphos (26.7 mg, 0.046 mmol) in toluene (2 mL) under N2 was heated at 100° C. for 21 h. The mixture was cooled to rt and diluted with DCM-MeOH (8:2). The mixture was filtered and the filtrates were concentrated. Purification of the residue by flash chromatography over silica gel, using 40% EtOAc in hexane, and following the second purification by flash chromatography over silica gel, using 10% MeOH in DCM, gave 6-chloro-7-methoxy-2,3-dimethyl-4-(3,3,7-trimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)quinoline. 1H-NMR (DMSO-d6) δ 7.40 (1H, s), 7.09 (1H, s), 7.07 (1H, d, J=8.0 Hz), 6.72 (1H, d, J=8.0 Hz), 4.01 (3H, s), 3.93 (1H, d, J=8.0 Hz), 3.80-3.62 (4H, m), 3.53 (1H, d, J=8.0 Hz), 3.00-2.90 (2H, m), 2.75-2.69 (2H, m), 2.61 (3H, s), 2.42 (3H, s), 1.70 (3H, s), 1.33 (3H, s), 1.09 (3H, s). Mass Spectrum (ESI) m/e=466.1 (M+1).

Aufarbeitung

  1. temperatureThe mixture was cooled to rt
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrates were concentrated
  4. customPurification of the residue by flash chromatography over silica gel
  5. customthe second purification by flash chromatography over silica gel

Quellen und Nachweise

ORD-Eintrag
ord-b509669c8c3847a093679d59aff644e6
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765940B2

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