2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(4-{4-[(4,5-dichloro-1-ethyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazin-1-yl)-benzoic acid tert-butyl ester

HRID 1645360Notes

Reaction equation

HRID 1645360 reaction equation
Cl.[N:2]1([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[N:18]([CH2:28][CH3:29])[C:19]4[C:24]([CH:25]=3)=[C:23]([Cl:26])[C:22]([Cl:27])=[CH:21][CH:20]=4)=[O:16])=[CH:10][CH:9]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[C:30]([O:34][C:35](=[O:43])[C:36]1[CH:41]=[CH:40][C:39](Br)=[CH:38][CH:37]=1)([CH3:33])([CH3:32])[CH3:31].CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].O1CCOCC1>[C:30]([O:34][C:35](=[O:43])[C:36]1[CH:41]=[CH:40][C:39]([N:5]2[CH2:6][CH2:7][N:2]([C:8]3[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]4[N:18]([CH2:28][CH3:29])[C:19]5[C:24]([CH:25]=4)=[C:23]([Cl:26])[C:22]([Cl:27])=[CH:21][CH:20]=5)=[O:16])=[CH:10][CH:9]=3)[CH2:3][CH2:4]2)=[CH:38][CH:37]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 11334366Tert-butyl 4-bromobenzoateHCID 23676156Sodium t-butoxideHCID 667723914,5-Dichloro-1-ethyl-1h-indole-2-carboxylic acid (4-piperazin-1-yl-phenyl)-amide hydrochloride salt

Product 1

HCID 667720684-(4-{4-[(4,5-dichloro-1-ethyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazin-1-yl)-benzoic acid tert-butyl esterYield 49.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture containing 4,5-dichloro-1-ethyl-1H-indole-2-carboxylic acid (4-piperazin-1-yl-phenyl)-amide hydrochloride (110 mg, 0.24 mmol), dioxane (6 mL), 4-bromo-benzoic acid tert-butyl ester (160 mg, 0.62 mmol), sodium tert-butoxide (128 mg, 1.33 mmol), Pd2(dba)3 (20 mg, 5% mol) and X-PHOS ligand (35 mg) was stirred under Ar, and heated for 2 hours at 100° C. The mixture was concentrated to dryness. The residue was taken up in 50 mL of EtOAc and washed with 50 mL of water, brine and dried with anhydrous sodium sulfate. The solvent was removed and the residue was triturated with methanol followed by hexanes. The solid was filtered to give 4-(4-{4-[(4,5-dichloro-1-ethyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazin-1-yl)-benzoic acid tert-butyl ester (70 mg).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. washwashed with 50 mL of water, brine
  3. dry with materialdried with anhydrous sodium sulfate
  4. customThe solvent was removed
  5. customthe residue was triturated with methanol
  6. filtrationThe solid was filtered

Sources & evidence

ORD record
ord-ff1f98ca95b140189a3d619f839f0365
Source dataset
uspto-grants-2012_02
Patent number
US08124766B2

Reaction notes

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