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

HRID 1625515노트

반응식

HRID 1625515 반응식
[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

참가 물질

6

반응물 3

HCID 6344DichloromethaneHCID 66111TrimethylsilylacetyleneHCID 178461439HCID 178461439, 화합물

생성물 1

HCID 178461440tert-butyl (2S,4S)-4-methyl-2-[5-[4-(2-trimethylsilylethynyl)phenyl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate수율 48.2%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-fc3ddfb0effd42498287c542789619cc
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

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