Dimethylformamide → (3R,3aS,6aR)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 29173Notes

Reaction equation

HRID 29173 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 21356327(3R,3aS,6aR)Hexahydrofuro[2,3-b]furan-3-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)amino-2-hydroxypropyl)carbamateHCID 21936557DiisopropyldiethylamineHCID 229970162-[(Methylsulfonyl)amino]benzimidazol-5-ylsulfonyl chloride

Product 1

HCID 86585030(3R,3aS,6aR)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

(3R,3aS,6aR)Hexahydrofuro[2,3-b]furan-3-yl-N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)amino-2-hydroxypropyl)carbamate (Step 2, Example 54), (0.065 g, 0.2 mmol) was combined with 2-[(methylsulfonyl)amino]benzimidazol-5-ylsulfonyl chloride (0.071 g, 0.2 mmol) in anhydrous DMF (2 ml) under a N2 atmosphere. The resulting solution was chilled to 0° C. and diisopropylethylethyl amine (0.080 ml, 0.5 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=0.53 (5% MeOH/EtOAc). 1H NMR (CDCl3) 8.09 (1H,s), 7.69 (1H,d), 7.43 (1H,d), 7.32-7.08 (5H,m), 6.31-6.18 (2H,m), 5.71-5.59 (2H,m), 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)+ 694.0.

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-4d2a0ec4d66b40f79cc9b7232e82f5a6
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

Loading…