Potassium Carbonate → 5{[2-fluoro-4-(1H-indol-5-yl)phenyl]methyl}-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

HRID 341057

反応式

HRID 341057 の反応式
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]2=[N:20][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:22](=[O:23])[C:12]2=[CH:11]1.[NH:31]1[C:39]2[C:34](=[CH:35][C:36](B(O)O)=[CH:37][CH:38]=2)[CH:33]=[CH:32]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CS(C)=O>[F:1][C:2]1[CH:7]=[C:6]([C:36]2[CH:35]=[C:34]3[C:39](=[CH:38][CH:37]=2)[NH:31][CH:32]=[CH:33]3)[CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]2=[N:20][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:22](=[O:23])[C:12]2=[CH:11]1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 27343615-Indolylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 671125025-[(2-fluoro-4-iodophenyl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazol[4,3-c]quinolin-3-one

生成物 1

HCID 681542165{[2-fluoro-4-(1H-indol-5-yl)phenyl]methyl}-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

実験手順

5-[(2-Fluoro-4-iodophenyl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazol[4,3-c]quinolin-3-one (51 mg, 0.10 mmol), 1H-indol-5-ylboronic acid (27 mg, 0.17 mmol, 1.7 equiv), potassium carbonate (34 mg, 0.25 mmol, 2.5 equiv), palladium(II) acetate (12 mg, 0.0010 mmol, 0.1 equiv) and 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (14 mg, 0.030 mmol, 0.3 equiv) were combined in water (0.1 mL) and dimethylsulfoxide (0.5 mL) and placed into a preheated oil bath at 85° C. for 90 minutes. The mixture was cooled to ambient temperature, filtered and purified by reverse phase HPLC (80:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 11.18 (1H, s), 9.11 (1H, s), 8.22 (1H, dd, J=7.9, 1.5 Hz), 7.85 (1H, s), 7.79 (1H, d, J=8.7 Hz), 7.68 (1H, ddd, J=8.5, 7.3, 1.6 Hz), 7.62 (1H, dd, J=7.9, 1.7 Hz), 7.60 (1H, br s), 7.57 (1H, s), 7.55 (1H, d, J=7.4 Hz), 7.49 (1H, dd, J=8.1, 1.8 Hz), 7.47-7.37 (4H, m), 7.34 (1H, td, J=7.5, 1.4 Hz), 7.28 (1H, t, J=8.2 Hz), 6.48-6.47 (1H, m), 5.83 (2H, s) ppm; low resolution mass spectrometry (ES+) m/z 503.1667 [(M+H)+; calculated for C31H21F2N4O: 503.1678].

後処理

  1. filtrationfiltered
  2. custompurified by reverse phase HPLC (80:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-7ca1d30d8b514f25b561b77cfb585fbb
出典データセット
uspto-grants-2014_11
特許番号
US08895580B2

関連ノート

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