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 1618614ノート

反応式

HRID 1618614 の反応式
[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

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b509669c8c3847a093679d59aff644e6
出典データセット
uspto-grants-2014_07
特許番号
US08765940B2

反応ノート

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