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 1625516ノート

反応式

HRID 1625516 の反応式
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]

参加物

8

反応物 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

生成物 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-carboxylate収率 61.9%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

実験手順

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+).

後処理

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

出典と根拠

ORDレコード
ord-df585b1fe12d4c27a310eefe30b3be77
出典データセット
uspto-grants-2014_07
特許番号
US08779156B2

反応ノート

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