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 1618614노트

반응식

HRID 1618614 반응식
[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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 21226129Dichloromethane methanol용매

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온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b509669c8c3847a093679d59aff644e6
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765940B2

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