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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 629614
Notes
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Reaction equation

HRID 629614 reaction equation
[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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 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, compound

Product 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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4e127f12d008498988388a9bd94f3c27
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09315488B2

Reaction notes

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