Dichloromethane → tert-butyl (2S,4S)-4-methyl-2-[5-[4-(2-trimethylsilylethynyl)phenyl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate

HRID 1625515Notes

Reaction equation

[C:1]([Si:3]([CH3:6])([CH3:5])[CH3:4])#[CH:2].Br[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:35]=[CH:34][C:17]3[NH:18][C:19]([C@@H:21]4[CH2:25][C@H:24]([CH3:26])[CH2:23][N:22]4[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[N:20][C:16]=3[CH:15]=2)=[CH:10][CH:9]=1.C(Cl)Cl>[Cu]I.CN(C=O)C>[CH3:26][C@@H:24]1[CH2:23][N:22]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:21]([C:19]2[NH:18][C:17]3[CH:34]=[CH:35][C:14]([C:11]4[CH:12]=[CH:13][C:8]([C:2]#[C:1][Si:3]([CH3:6])([CH3:5])[CH3:4])=[CH:9][CH:10]=4)=[CH:15][C:16]=3[N:20]=2)[CH2:25]1

Participants

Conditions

Temperature: 70 °C

Procedure

Ethynyl-trimethyl-silane (34.44 mg, 49.55 μL, 0.3506 mmol), tert-butyl (2S,4S)-2-[5-(4-bromophenyl)-1H-benzimidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (80 mg, 0.1753 mmol), Pd(DPPF)(Cl)2.CH2Cl2(14.32 mg, 0.01753 mmol), TEA (35.48 mg, 48.87 μL, 0.3506 mmol) and CuI (3.339 mg, 0.01753 mmol) are dissolved to dry DMF (2 mL). The mixture is stirred at 70° C. under N2 overnight. After removal of the solvent under reduced pressure, the residue is purified by flash column chromatography on silica gel SP1 25M using methanol/CH2Cl2 (0-5%) in 20 cv to provide tert-butyl (2S,4S)-4-methyl-2-[5-[4-(2-trimethylsilylethynyl)phenyl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate (40 mg).

Workup

customAfter removal of the solvent under reduced pressure
customthe residue is purified by flash column chromatography on silica gel SP1 25M

Sources & evidence

ORD record: ord-fc3ddfb0effd42498287c542789619cc
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08779156B2

Reaction notes

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