Dimethylformamide → (3S,3aR,6aS)Hexahydrofuro[2,3-b]furan-3-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy) (2-[(methylsulfonyl)amino]benzimidazol-5-ylsulfonyl)amino-2-hydroxypropyl)carbamate

HRID 29172Notes

Reaction equation

HRID 29172 reaction equation
[O:1]1[C@@H:5]2[O:6][CH2:7][CH2:8][C@@H:4]2[C@H:3]([O:9][C:10](=[O:30])[NH:11][C@@H:12]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@H:13]([OH:22])[CH2:14][NH:15]OC2CCCC2)[CH2:2]1.[CH3:31][S:32]([NH:35][C:36]1[NH:37][C:38]2[CH:44]=[C:43]([S:45](Cl)(=[O:47])=[O:46])[CH:42]=[CH:41][C:39]=2[N:40]=1)(=[O:34])=[O:33].[CH:49]([C:52]([CH:57]([CH3:59])C)(NCC)C)([CH3:51])C.CN(C=[O:64])C>CCOC(C)=O>[O:1]1[C@@H:5]2[O:6][CH2:7][CH2:8][C@@H:4]2[C@H:3]([O:9][C:10](=[O:30])[NH:11][C@@H:12]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:13]([OH:22])[CH:14]([NH:15][S:45]([C:43]2[CH:42]=[CH:41][C:39]3[N:40]=[C:36]([NH:35][S:32]([CH3:31])(=[O:34])=[O:33])[NH:37][C:38]=3[CH:44]=2)(=[O:47])=[O:46])[O:64][CH:49]2[CH2:52][CH2:57][CH2:59][CH2:51]2)[CH2:2]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 21936557DiisopropyldiethylamineHCID 229970162-[(Methylsulfonyl)amino]benzimidazol-5-ylsulfonyl chlorideHCID 86585028(3S,3aR,6aS) Hexahydrofuro[2,3-b]furan-3-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)amino-2-hydroxypropyl)carbamate

Product 1

HCID 86585027(3S,3aR,6aS)Hexahydrofuro[2,3-b]furan-3-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy) (2-[(methylsulfonyl)amino]benzimidazol-5-ylsulfonyl)amino-2-hydroxypropyl)carbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(3S,3aR,6aS) Hexahydrofuro[2,3-b]furan-3-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)amino-2-hydroxypropyl)carbamate (0.050 g, 0.1 mmol) was combined with 2-[(methylsulfonyl)amino]benzimidazol-5-ylsulfonyl chloride (0.055 g, 0.2 mmol) in anhydrous DMF (1 ml) under a N2 atmosphere. The resulting solution was chilled to 0° C. and diisopropylethylethyl amine (0.062 ml, 0.4 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 preparative TLC (5% MeOH/EtOAc). Recovered 0.051 g (62%) of the product as a white foam. Rf=0.42 (5% MeOH/EtOAc). 1H NMR (CDCl3) 8.09 (1H,s), 7.76 (1H,d), 7.39 (1H,d), 7.32-7.12 (5H,m), 6.54-6.40 (2H,m), 5.67 (1H,d), 5.10-4.92 (2H,m), 4.85 (1H,m), 4.00-3.83 (3H,m), 3.82-3.70 (2H,m), 3.62-3.51 (1H,m), 3.38 (1H,m), 3.31 (3H,s), 3.10 (1H,m), 3.04-2.80 (4H,m), 1.92-1.70 (6H,m), 1.69-1.44 (4H,m). LRMS (M+H)+ 694.1.

Workup

  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 preparative TLC (5% MeOH/EtOAc)
  7. customRecovered 0.051 g (62%) of the product as a white foam

Sources & evidence

ORD record
ord-b76a50a684984b2fb7f6c3147955c0b5
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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