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 1429256노트

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HRID 1429256 반응식
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]

참가 물질

7

반응물 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

생성물 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-carboxylate수율 41%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

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온도
-20 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-c69922b35acd4d2cb7c114ed53ce18b7
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08937150B2

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