Methanesulfonyl chloride → Methanesulfonic acid 3-{1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-methanoyl}-4-methoxy-phenyl Ester

HRID 2230724Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2230724
[CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[N:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C@:24]2([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:28][CH2:27][N:26]([C:29]([C:31]3[CH:36]=[C:35]([OH:37])[CH:34]=[CH:33][C:32]=3[O:38][CH3:39])=[O:30])[CH2:25]2)[CH2:17][CH2:16]1)[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:55][S:56](Cl)(=[O:58])=[O:57]>ClCCl>[CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[N:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH2:23][C@:24]2([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:28][CH2:27][N:26]([C:29]([C:31]3[CH:36]=[C:35]([O:37][S:56]([CH3:55])(=[O:58])=[O:57])[CH:34]=[CH:33][C:32]=3[O:38][CH3:39])=[O:30])[CH2:25]2)[CH2:17][CH2:16]1)[CH3:2]

Komponenten

5

Edukt 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 701487941-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-(5-hydroxy-2-methoxy-phenyl)-methanone

Produkt 1

HCID 59902263Methanesulfonic acid 3-{1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-methanoyl}-4-methoxy-phenyl EsterAusbeute 125,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Treat a stirred solution of 1-[(R)-3-(2-{4-[1-(2-ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-(5-hydroxy-2-methoxy-phenyl)-methanone (0.25 g, 0.22 mmol) and dichloromethane (5 mL) at 0° C. with diisopropylethylamine (0.14 mL, 0.84 mmol) and methane sulfonyl chloride (0.04 mL, 0.5 mmol). Stir the reaction mixture at 0° C. for two hours, dilute with dichloromethane and wash with water. Dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Purify the product by column chromatography (silica gel, elute sequentially with 3% methanol in dichloromethane then with 5% methanol in dichloromethane) and concentrate the appropriate fractions to afford 0.19 g of the title compound, Rf=0.28 (silica gel, 5% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods swell known in the art.

Aufarbeitung

  1. washwash with water
  2. dry with materialDry (MgSO4) the organic phase
  3. filtrationfilter
  4. concentrationconcentrate the filtrate in vacuo
  5. customPurify the product by column chromatography (silica gel
  6. washelute sequentially with 3% methanol in dichloromethane
  7. concentrationwith 5% methanol in dichloromethane) and concentrate the appropriate fractions

Quellen und Nachweise

ORD-Eintrag
ord-d8a75b4628324e1c8aa2cac7d03ca4dc
Quelldatensatz
uspto-grants-2002_07
Patentnummer
US06423704B1

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