Water → tert-butyl (2S,4S)-2-[4-[2-[4-[2-[(2S,4S)-1-tert-butoxycarbonyl-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]ethynyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate

HRID 1625516노트

반응식

HRID 1625516 반응식
I[C:2]1[N:3]=[C:4]([C@@H:7]2[CH2:11][C@H:10]([CH3:12])[CH2:9][N:8]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[NH:5][CH:6]=1.[CH3:20][C@@H:21]1[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:23]([C:33]2[NH:37][C:36]3C=C[C:40]([C:42]4[CH:47]=[CH:46][C:45]([C:48]#[C:49][Si](C)(C)C)=[CH:44][CH:43]=4)=[CH:41][C:35]=3[N:34]=2)[CH2:22]1.C(Cl)Cl.[CH2:57]1CCN2C(=NCCC2)C[CH2:58]1.O>CN(C=O)C.[Cu]I>[C:16]([O:15][C:13]([N:8]1[CH2:9][C@@H:10]([CH3:12])[CH2:11][C@H:7]1[C:4]1[NH:5][C:6]2[CH:57]=[CH:58][C:48]([C:45]3[CH:46]=[CH:47][C:42]([C:40]#[C:41][C:35]4[N:34]=[C:33]([C@@H:23]5[CH2:22][C@H:21]([CH3:20])[CH2:25][N:24]5[C:26]([O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[O:27])[NH:37][CH:36]=4)=[CH:43][CH:44]=3)=[CH:49][C:2]=2[N:3]=1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

참가 물질

8

반응물 5

HCID 962WaterHCID 6344DichloromethaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 53261949(2S,4S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylateHCID 178461440tert-butyl (2S,4S)-4-methyl-2-[5-[4-(2-trimethylsilylethynyl)phenyl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate

생성물 1

HCID 178461457tert-butyl (2S,4S)-2-[4-[2-[4-[2-[(2S,4S)-1-tert-butoxycarbonyl-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]ethynyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate수율 61.9%

시약·촉매·용매 2

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

실험 절차

The well-degassed solution of tert-butyl (2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (38.21 mg, 0.1013 mmol), tert-butyl (2S,4S)-4-methyl-2-[5-[4-(2-trimethylsilylethynyl)phenyl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate (40 mg, 0.08444 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (6.896 mg, 0.008444 mmol), CuI (3.217 mg, 0.01689 mmol), DBU (128.5 mg, 126.2 μL, 0.8444 mmol), and water (4.563 mg, 4.563 μL, 0.2533 mmol) in DMF (3 mL) 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 using methanol/CH2Cl2 (0-6%) to provide the desired tert-butyl (2S,4S)-2-[4-[2-[4-[2-[(2S,4S)-1-tert-butoxycarbonyl-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]ethynyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (34 mg, 61.8% yield). LC/MS: m/z=651.42 (M+H+).

후처리

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

출처 및 근거

ORD 기록
ord-df585b1fe12d4c27a310eefe30b3be77
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

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