Triethylamine → di-tert-butyl (2S,2'S)-2,2'-{[(2R,5R)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl]bis(6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylate

HRID 1411436ノート

反応式

HRID 1411436 の反応式
O[C@H:2]([C:37]1[C:65]([F:66])=[CH:64][C:40]2[N:41]([CH2:56][O:57][CH2:58][CH2:59][Si:60]([CH3:63])([CH3:62])[CH3:61])[C:42]([C@@H:44]3[CH2:48][CH2:47][CH2:46][N:45]3[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[N:43][C:39]=2[CH:38]=1)[CH2:3][CH2:4][C@@H:5]([C:7]1[C:35]([F:36])=[CH:34][C:10]2[N:11]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:12]([C@@H:14]3[CH2:18][CH2:17][CH2:16][N:15]3[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[N:13][C:9]=2[CH:8]=1)O.C(N(CC)CC)C.S(Cl)(C)(=O)=O.[C:79]([C:83]1[CH:89]=[CH:88][C:86]([NH2:87])=[CH:85][CH:84]=1)([CH3:82])([CH3:81])[CH3:80]>C(Cl)Cl.CCOC(C)=O>[C:79]([C:83]1[CH:84]=[CH:85][C:86]([N:87]2[C@@H:2]([C:37]3[C:65]([F:66])=[CH:64][C:40]4[N:41]([CH2:56][O:57][CH2:58][CH2:59][Si:60]([CH3:62])([CH3:61])[CH3:63])[C:42]([C@@H:44]5[CH2:48][CH2:47][CH2:46][N:45]5[C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])=[N:43][C:39]=4[CH:38]=3)[CH2:3][CH2:4][C@@H:5]2[C:7]2[C:35]([F:36])=[CH:34][C:10]3[N:11]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:32])[CH3:33])[C:12]([C@@H:14]4[CH2:18][CH2:17][CH2:16][N:15]4[C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])=[N:13][C:9]=3[CH:8]=2)=[CH:88][CH:89]=1)([CH3:82])([CH3:80])[CH3:81]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 698614-Tert-ButylanilineHCID 58403917di-tert-butyl (2S,2'S)-2,2'-{[(1S,4S)-1,4-dihydroxybutane-1,4-diyl]bis (6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylate

生成物 1

HCID 58403909di-tert-butyl (2S,2'S)-2,2'-{[(2R,5R)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl]bis(6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylate収率 41%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-20 °C

実験手順

To a solution of di-tert-butyl (2S,2′S)-2,2′-{[(1S,4S)-1,4-dihydroxybutane-1,4-diyl]bis(6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylate (100 mg, 0.10 mmol) in CH2Cl2 (1 mL) at −20° C. was added triethylamine (0.044 mL, 0.31 mmol) followed by mesyl chloride (0.018 mL, 0.23 mmol) and the solution stirred at −20° C. for 1 hour. 4-tert-Butyl aniline (0.083 mL, 0.52 mmol) was added in one portion, and the solution was allowed to warm to room temperature overnight, with stirring. The solution was diluted with EtOAc, washed with 1N HCl, H2O, and brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (0-50% EtOAc/hexane) gave the title compound (46 mg, 0.04 mmol, 41%).

後処理

  1. temperatureto warm to room temperature overnight
  2. stirringwith stirring
  3. washwashed with 1N HCl, H2O, and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (0-50% EtOAc/hexane)

出典と根拠

ORDレコード
ord-646aceba25444cb7be4136124000dadd
出典データセット
uspto-grants-2014_12
特許番号
US08921514B2

反応ノート

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