HCID 178435594, compound → HCID 178525130, compound

HRID 1804667Notes

Reaction equation

HRID 1804667 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[C:17]1[NH:21][C:20]2[CH:22]=[CH:23][C:24]([C:26]#[CH:27])=[CH:25][C:19]=2[N:18]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1.[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>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[C:17]1[NH:21][C:20]2[CH:22]=[CH:23][C:24]([C:26]#[C:27][C:27]#[C:26][C:24]3[CH:23]=[CH:22][C:20]4[NH:21][C:17]([C@@H:12]5[CH2:13][CH2:14][CH2:15][CH2:16][N:11]5[C:9]([O:8][CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[O:10])=[N:18][C:19]=4[CH:25]=3)=[CH:25][C:19]=2[N:18]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 1

HCID 178435594HCID 178435594, compound

Product 1

HCID 178525130HCID 178525130, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178419050HCID 178419050, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of (S)-2-(5-ethynyl-1H-benzoimidazol-2-yl)-piperidine-1-carboxylic acid benzyl ester (26 mg, 0.0723 mmol), CuI (3 mg) and bis(triphenylphosphine)palladium (II) dichloride (8 mg) in THF (1.5 mL) is added TEA (30 μL, 3.4 mmol). The reaction mixture is stirred at room temperature for 12 hours and filtered through celite and the filtrate is concentrated in vacuum to dryness. The residue is purified by flash column chromatography on silica gel (EtOAc/hexanes 0% to 100%) to give the title compound (S)-2-(5-{4-[2-((S)-1-benzyloxycarbonyl-piperidin-2-yl)-1H-benzoimidazol-5-yl]-buta-1,3-diynyl}-1H-benzoimidazol-2-yl)-piperidine-1-carboxylic acid benzyl ester (10 mg, 39%).

Workup

  1. filtrationfiltered through celite
  2. concentrationthe filtrate is concentrated in vacuum to dryness
  3. customThe residue is purified by flash column chromatography on silica gel (EtOAc/hexanes 0% to 100%)

Sources & evidence

ORD record
ord-8cdc8b52bb134b70a7905f82927f403b
Source dataset
uspto-grants-2013_01
Patent number
US08354419B2

Reaction notes

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