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 1411436Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1411436
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]

Komponenten

7

Edukt 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

Produkt 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-carboxylateAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-646aceba25444cb7be4136124000dadd
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921514B2

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