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2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → 4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-n-({4-[2-(1,3-dioxolan-2-yl)ethyl]-3-nitrophenyl}sulfonyl)-2-(1h-indol-5-yloxy)benzamide

HRID 2168376
ノート
印刷プレビュー

反応式

HRID 2168376 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[CH:32]=[C:31]([N:33]4[CH2:38][CH2:37][N:36]([CH2:39][C:40]5[CH2:45][CH2:44][C:43]([CH3:47])([CH3:46])[CH2:42][C:41]=5[C:48]5[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=5)[CH2:35][CH2:34]4)[CH:30]=[CH:29][C:12]=3[C:13]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22](Cl)=[C:21]([N+:26]([O-:28])=[O:27])[CH:20]=3)(=[O:18])=[O:17])=[O:14])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[Br-].[O:85]1[CH2:89][CH2:88][O:87][CH:86]1[CH2:90][CH2:91][Zn+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:54][C:51]1[CH:52]=[CH:53][C:48]([C:41]2[CH2:42][C:43]([CH3:46])([CH3:47])[CH2:44][CH2:45][C:40]=2[CH2:39][N:36]2[CH2:35][CH2:34][N:33]([C:31]3[CH:30]=[CH:29][C:12]([C:13]([NH:15][S:16]([C:19]4[CH:24]=[CH:23][C:22]([CH2:91][CH2:90][CH:86]5[O:87][CH2:88][CH2:89][O:85]5)=[C:21]([N+:26]([O-:28])=[O:27])[CH:20]=4)(=[O:18])=[O:17])=[O:14])=[C:11]([O:10][C:6]4[CH:5]=[C:4]5[C:9](=[CH:8][CH:7]=4)[NH:1][CH:2]=[CH:3]5)[CH:32]=3)[CH2:38][CH2:37]2)=[CH:49][CH:50]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 672283542-(1h-Indol-5-yloxy)-n-(4-chloro-3-nitrophenylsulfonyl)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)benzamideHCID 178419780HCID 178419780、化合物

生成物 1

HCID 468329744-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-n-({4-[2-(1,3-dioxolan-2-yl)ethyl]-3-nitrophenyl}sulfonyl)-2-(1h-indol-5-yloxy)benzamide

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of EXAMPLE 187A (0.079 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.016 g), and palladium acetate (0.0045 g) in tetrahydrofuran (1 mL) was stirred at room temperature for 5 minutes. To this mixture was added (2-(1,3-dioxolan-2-yl)ethyl)zinc(II) bromide (0.6 mL). The reaction mixture was stirred overnight. The solvent was removed, and the residue was purified by reverse phase Prep HPLC. The desired fractions were combined, and the organic solvent was partially removed. The resulting mixture was treated with saturated aqueous NaHCO3, extracted with ethyl acetate, dried over MgSO4, filtered, and concentrated to give the title compound. 1H NMR (500 MHz, dimethylsulfoxide-d6) δ 11.14 (s, 1H), 8.37 (s, 1H), 8.00 (s, 1H), 7.55 (br s., 1H), 7.52 (d, 1H), 7.33-7.39 (m, 4H), 7.08 (br s, 1H), 7.04 (d, 2H), 6.83 (dd, 1H), 6.62 (d, 1H), 6.38 (s, 1H), 6.15 (d, 1H), 4.85 (t, 1H), 3.87-3.89 (m, 2H), 3.76-3.79 (m, 2H), 3.04 (s, 4H), 2.91-2.94 (m, 2H), 2.11-2.15 (m, 4H), 1.88-1.91 (s, 4H), 1.39 (t, 2H), 0.92 (s, 6H).

後処理

  1. customThe solvent was removed
  2. customthe residue was purified by reverse phase Prep HPLC
  3. customthe organic solvent was partially removed
  4. additionThe resulting mixture was treated with saturated aqueous NaHCO3
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-a70227b65e77472f945366d3d5f768e8
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09045420B2

反応ノート

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