HCID 178435595, compound → HCID 178452388, compound

HRID 1804665Notes

Reaction equation

HRID 1804665 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[C@H:10]([C:24]2[NH:28][C:27]3[CH:29]=[CH:30][C:31]([C:33]#[CH:34])=[CH:32][C:26]=3[N:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:35]([O:42][C:43]([N:45]1[CH2:50][CH2:49][CH2:48][CH2:47][C@H:46]1[C:51]1[NH:55][C:54]2[CH:56]=[CH:57][C:58](I)=[CH:59][C:53]=2[N:52]=1)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C=O)C.CCOC(C)=O.O.[Cu]I.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[C@H:10]([C:24]2[NH:28][C:27]3[CH:29]=[CH:30][C:31]([C:33]#[C:34][C:57]4[CH:58]=[CH:59][C:53]5[NH:52][C:51]([C@@H:46]6[CH2:47][CH2:48][CH2:49][CH2:50][N:45]6[C:43]([O:42][CH2:35][C:36]6[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=6)=[O:44])=[N:55][C:54]=5[CH:56]=4)=[CH:32][C:26]=3[N:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 178435595HCID 178435595, compoundHCID 178525131HCID 178525131, compound

Product 1

HCID 178452388HCID 178452388, compoundYield 7,893.4%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of (S)-2-(5-ethynyl-1H-benzoimidazol-2-yl)-piperazine-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl ester (77 mg, 0.16 mmol), (S)-2-(5-iodo-1H-benzoimidazol-2-yl)-piperidine-1-carboxylic acid benzyl ester (70 mg, 0.15 mmol), CuI (3 mg, 0.015 mmol) and bis(triphenylphosphine)palladium (II) dichloride (10.6 mg, 0.015 mmol) in DMF (2 mL) is added TEA (0.1 mL, 0.76 mmol). The reaction mixture is stirred at room temperature for 2 hours, diluted with EtOAc and water. The mixture is filtered to remove insoluble material and the layers of the filtrate are separated. The organic layer is dried over sodium sulfate and concentrated in vacuum to dryness. The residue is purified by flash column chromatography on silica gel (MeOH/DCM 0% to 20%) and repurified by reverse phase HPLC using a gradient of CH3CN/water to give the title compound (9.4 g, 7%).

Workup

  1. filtrationThe mixture is filtered
  2. customto remove insoluble material
  3. customthe layers of the filtrate are separated
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated in vacuum to dryness
  6. customThe residue is purified by flash column chromatography on silica gel (MeOH/DCM 0% to 20%)
  7. customrepurified by reverse phase HPLC

Sources & evidence

ORD record
ord-c6591f90975e48ccbaef32550e95c6f6
Source dataset
uspto-grants-2013_01
Patent number
US08354419B2

Reaction notes

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