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

HRID 29193ノート

反応式

HRID 29193 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-b560d3bb0d90492281be85b407ef08ea
出典データセット
uspto-grants-2008_09
特許番号
US07419967B2

反応ノート

読み込み中…