Dichloromethane → HCID 178461451, compound

HRID 1625511Notes

Reaction equation

HRID 1625511 reaction equation
I[C:2]1[CH:23]=[CH:22][C:5]2[NH:6][C:7]([C@@H:9]3[CH2:13][C@H:12]([CH3:14])[CH2:11][N:10]3[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N:8][C:4]=2[CH:3]=1.[C:24]([C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:33]=[C:34]([C@@H:37]3[CH2:41][C@H:40]([CH3:42])[CH2:39][N:38]3[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[NH:35][CH:36]=2)=[CH:28][CH:27]=1)#[CH:25].C(Cl)Cl>CN(C=O)C.[Cu]I>[C:18]([O:17][C:15]([N:10]1[CH2:11][C@@H:12]([CH3:14])[CH2:13][C@H:9]1[C:7]1[NH:6][C:5]2[CH:22]=[CH:23][C:2]([C:25]#[C:24][C:26]3[CH:31]=[CH:30][C:29]([C:32]4[N:33]=[C:34]([C@@H:37]5[CH2:41][C@H:40]([CH3:42])[CH2:39][N:38]5[C:43]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:44])[NH:35][CH:36]=4)=[CH:28][CH:27]=3)=[CH:3][C:4]=2[N:8]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 178435838HCID 178435838, compoundHCID 178461441HCID 178461441, compound

Product 1

HCID 178461451HCID 178461451, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl (2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (68.5 mg, 0.16 mmol) in DMF (3 mL) are sequentially added tert-butyl (2S,4S)-2-[4-(4-ethynylphenyl)-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (47 mg, 0.13 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (5.4 mg, 0.0067 mmol). The mixture is degassed well under vacuum and to it is added TEA (37 uL, 0.27 mmol), followed by CuI (1.2 mg, 0.0067 mmol). Then the reaction mixture is stirred under nitrogen at rt overnight. After removal of the solvent, the crude is purified by flash column chromatography on silica gel using methanol/CH2Cl2 0-5% to obtain tert-butyl (2S,4S)-2-[4-[4-[2-[2-[(2S,4S)-1-tert-butoxycarbonyl-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]ethynyl]phenyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (56 mg, 64%).

Workup

  1. customThe mixture is degassed well under vacuum and to it
  2. customAfter removal of the solvent
  3. customthe crude is purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-eb0c27234095481799961ed2036c5725
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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