Dimethylformamide → 1,3-Dioxan-5-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)(2-[(methylsulfonyl)amino)benzimidazol-5-ylsulfonyl)amino-2-hydroxypropyl)carbamate

HRID 29193Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 29193
[O:1]1[CH2:6][CH:5]([O:7][C:8](=[O:28])[NH:9][C@@H:10]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:11]([OH:20])[CH2:12][NH:13]OC2CCCC2)[CH2:4][O:3][CH2:2]1.[CH3:29][S:30]([NH:33][C:34]1[NH:35][C:36]2[CH:42]=[C:41]([S:43](Cl)(=[O:45])=[O:44])[CH:40]=[CH:39][C:37]=2[N:38]=1)(=[O:32])=[O:31].[CH:47]([C:50]([CH:55]([CH3:57])C)(NCC)C)([CH3:49])C.CN(C=[O:62])C>CCOC(C)=O>[O:3]1[CH2:4][CH:5]([O:7][C:8](=[O:28])[NH:9][C@@H:10]([CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@@H:11]([OH:20])[CH:12]([NH:13][S:43]([C:41]2[CH:40]=[CH:39][C:37]3[N:38]=[C:34]([NH:33][S:30]([CH3:29])(=[O:32])=[O:31])[NH:35][C:36]=3[CH:42]=2)(=[O:45])=[O:44])[O:62][CH:47]2[CH2:50][CH2:55][CH2:57][CH2:49]2)[CH2:6][O:1][CH2:2]1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 213562831,3-Dioxan-5-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)amino-2-hydroxypropyl)carbamateHCID 21936557DiisopropyldiethylamineHCID 229970162-[(Methylsulfonyl)amino]benzimidazol-5-ylsulfonyl chloride

Produkt 1

HCID 865924451,3-Dioxan-5-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)(2-[(methylsulfonyl)amino)benzimidazol-5-ylsulfonyl)amino-2-hydroxypropyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

1,3-Dioxan-5-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)amino-2-hydroxypropyl)carbamate (Step 1, Example 55), (0.148 g, 0.4 mmol) was combined with 2-[(methylsulfonyl)amino]benzimidazol-5-ylsulfonyl chloride (0.162 g, 0.5 mmol) in anhydrous DMF (4 ml) under a N2 atmosphere. The resulting solution was chilled to 0° C. and diisopropylethylethyl amine (0.196 ml, 1.1 mmol) was added. The reaction was allowed to warm to room temperature and stirred for 24 hours. Reaction mixture was diluted in EtOAc and washed with sat. NaHCO3, 0.5N KHSO4 and brine. Organic phase was dried with MgSO4 and solvent was removed in vacuo. Purification by flash chromatography (EtOAc to 2% MeOH/EtOAc to 4%). Recovered 0.159 g (64%) of the product as a white foam. Rf=0.48 (5% MeOH/EtOAc). 1H NMR (CDCl3) 8.10 (1H,s), 7.67 (1H,d), 7.41 (1H,d), 7.30-7.15 (5H,m), 6.35 (2H,s), 5.14 (1H,d), 4.90 (1H,d), 4.85 (1H,m), 4.72 (1H,d), 4.48 (1H,m), 3.93-3.73 (5H,m), 3.29 (3H,s), 1.89-1.70 (4H,m), 1.69-1.47 (4H,m). LRMS (M+H)+ 668.0.

Aufarbeitung

  1. temperatureto warm to room temperature
  2. customReaction mixture
  3. washwashed with sat. NaHCO3, 0.5N KHSO4 and brine
  4. dry with materialOrganic phase was dried with MgSO4 and solvent
  5. customwas removed in vacuo
  6. customPurification by flash chromatography (EtOAc to 2% MeOH/EtOAc to 4%)
  7. customRecovered 0.159 g (64%) of the product as a white foam

Quellen und Nachweise

ORD-Eintrag
ord-b560d3bb0d90492281be85b407ef08ea
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419967B2

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