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

HRID 29193노트

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HRID 29193 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b560d3bb0d90492281be85b407ef08ea
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07419967B2

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