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 1166483Notes

Reaction equation

HRID 1166483 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-88861dd825cb4b63a5b6397b4354939c
Source dataset
uspto-grants-2003_09
Patent number
US06613743B2

Reaction notes

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