2-(1H-imidazol-1-yl)ethanamine → (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-{4-[({[2-(1H-imidazol-1-yl)ethyl]amino}carbonyl) oxy]benzyl}propylcarbamate

HRID 1253977Notes

Reaction equation

HRID 1253977 reaction equation
[C:1](=O)([O:43]C1C=CC([N+]([O-])=O)=CC=1)[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C@H:10]([NH:31][C:32]([O:34][C@@H:35]2[C@H:42]3[C@H:38]([O:39][CH2:40][CH2:41]3)[O:37][CH2:36]2)=[O:33])[C@H:11]([OH:30])[CH2:12][N:13]([S:18]([C:21]2[CH:29]=[CH:28][C:24]3[O:25][CH2:26][O:27][C:23]=3[CH:22]=2)(=[O:20])=[O:19])[CH2:14][CH:15]([CH3:17])[CH3:16])=[CH:5][CH:4]=1.[N:54]1([CH2:59][CH2:60][NH2:61])[CH:58]=[CH:57][N:56]=[CH:55]1>O1CCOCC1.C(OCC)(=O)C>[O:25]1[C:24]2[CH:28]=[CH:29][C:21]([S:18]([N:13]([CH2:14][CH:15]([CH3:16])[CH3:17])[CH2:12][C@@H:11]([OH:30])[C@@H:10]([NH:31][C:32](=[O:33])[O:34][C@@H:35]3[C@H:42]4[C@H:38]([O:39][CH2:40][CH2:41]4)[O:37][CH2:36]3)[CH2:9][C:6]3[CH:5]=[CH:4][C:3]([O:2][C:1]([NH:61][CH2:60][CH2:59][N:54]4[CH:58]=[CH:57][N:56]=[CH:55]4)=[O:43])=[CH:8][CH:7]=3)(=[O:20])=[O:19])=[CH:22][C:23]=2[O:27][CH2:26]1

Participants

5

Reactant 2

HCID 4306672-(1H-imidazol-1-yl)ethanamineHCID 599972454-{(2S,3R)-2-({[(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl)amino)-4-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-3-hydroxybutyl}phenyl 4-nitrophenyl carbonate

Product 1

HCID 59997251(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-{4-[({[2-(1H-imidazol-1-yl)ethyl]amino}carbonyl) oxy]benzyl}propylcarbamateYield 48.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-{(2S,3R)-2-({[(3R,3aS,6aR)-Hexahydrofuro [2,3-b]furan-3-yloxy]carbonyl}amino)-4-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-3-hydroxybutyl}phenyl 4-nitrophenyl carbonate (50 mg, 0.07 mmol) in 1,4-dioxane (1 mL) was added 2-(1H-imidazol-1-yl)ethanamine (50 mg, 0.45 mmol, Synthetic Communications 1991, 21, 535-544) and the mixture was stirred at ambient temperature for 30 min. The mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate/water (4×), dried (sodium sulfate), evaporated and purified by chromatography (silica gel, dichloromethane/2M ethanolic ammonia, 93:7) to provide the title compound as a white solid (25 mg). 1H NMR (DMSO-d6): δ 0.78 (3H, d), 0.82 (3H, d), 1.2 (1H, dd), 1.4 (1H, quintuplet), 1.9-2.0 (1H, m), 2.4 (1H, t), 2.55-2.80 (3H, m), 2.9-3.0 (2H, m), 3.3-3.4 (3H, m), 3.5-3.6 (4H, m), 3.7 (1H, t), 3.8 (1H, dd), 4.03-4.07 (2H, m), 4.8 (1H, dt), 0.505 (1H, d), 5.5 (1H, d), 6.18 (2H, s), 6.87 (1H, s), 6.9 (2H, d), 7.05 (1H, d), 7.15 (1H, s), 7.2 (2H, d), 7.23 (1H, s), 7.25-7.30 (2H, m), 7.6 (1H, s), 7.8 (1H, t); MS: 730 (MH+)

Workup

  1. washwashed with saturated sodium bicarbonate/water (4×)
  2. dry with materialdried (sodium sulfate)
  3. customevaporated
  4. custompurified by chromatography (silica gel, dichloromethane/2M ethanolic ammonia, 93:7)

Sources & evidence

ORD record
ord-21e5d8a088f24206a6b037abb3b18273
Source dataset
uspto-grants-2013_06
Patent number
US08455497B2

Reaction notes

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