Water → HCID 90042013, compound

HRID 929211Notes

Reaction equation

HRID 929211 reaction equation
I([O-])(=O)(=O)=O.[Na+].[Cl:7][C:8]1[CH:9]=[C:10]2[NH:28][C:27]([O:29][C@@H:30]3[CH2:34][O:33][C@@H:32]4[C@:35]([CH2:39][CH:40]=[O:41])([OH:38])[CH2:36][O:37][C@H:31]34)=[N:26][C:11]2=[N:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:16][CH:15]=1.[OH2:42]>C(Cl)(Cl)(Cl)Cl.C(#N)C.O.[Ru](Cl)(Cl)Cl>[Cl:7][C:8]1[CH:9]=[C:10]2[NH:28][C:27]([O:29][C@@H:30]3[CH2:34][O:33][C@@H:32]4[C@:35]([CH2:39][C:40]([OH:42])=[O:41])([OH:38])[CH2:36][O:37][C@H:31]34)=[N:26][C:11]2=[N:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 962WaterHCID 23667635Sodium periodateHCID 90042613HCID 90042613, compound

Product 1

HCID 90042013HCID 90042013, compound

Reagents, catalysts & solvents 3

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 5943Carbon TetrachlorideSolventHCID 6342AcetonitrileSolvent

Procedure

Sodium periodate (41.5 mg, 0.194 mmol) and ruthenium (III) chloride hydrate (1.5 mg, 6.65 μmol) were added to a stirred solution of 2-[(3R,3aR,6R,6aS)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-6-hydroxy-3,3a,5,6a-tetrahydro-2H-furo[3,2-b]furan-6-yl]acetaldehyde (32.4 mg, 0.066 mmol) in carbon tetrachloride (0.2 ml), acetonitrile (0.2 ml), and water (0.26 ml). The reaction mixture was stirred at room temperature. After 6 hours, the reaction mixture was placed in the refrigerator overnight. In the morning, the reaction mixture was removed from the refrigerator and allowed to warm to room temperature. After 4 hours, the reaction mixture was partitioned between EtOAc (40 ml) and water (40 ml). The aqueous layer was extracted with EtOAc (2×20 ml). The organic layers were combined, dried over MgSO4, filtered, and evaporated under reduced pressure to give an off-white residue. This material was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a white solid. LC-MS: calculated for C26H22ClN3O6 507.12 observed m/e: 508.21 (M+H)+ (Rt 1.17/2 min); 1H NMR δ (ppm) (CD3OD): 7.97 (s, 1H), 7.74-7.77 (m, 4H), 7.70 (d, J=7.8 Hz, 2H), 7.48 (t, J=7.7 Hz, 2H), 7.38 (t, J=7.3 Hz, 1H), 5.58 (qt, J=5.4 Hz, J=10.8 Hz, 1H), 4.99 (t, J=5.4 Hz, 1H), 4.41 (d, J=4.9 Hz, 1H), 4.15-4.21 (m, 2H), 3.83 (abqt, J=8.9 Hz, J=69.3 Hz, 2H), 2.58-2.65 (m, 2H).

Workup

  1. customwas placed in the refrigerator overnight
  2. customIn the morning, the reaction mixture was removed from the refrigerator
  3. temperatureto warm to room temperature
  4. waitAfter 4 hours
  5. customthe reaction mixture was partitioned between EtOAc (40 ml) and water (40 ml)
  6. extractionThe aqueous layer was extracted with EtOAc (2×20 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customto give an off-white residue
  11. customThis material was purified by preparative HPLC reverse phase (C-18)
  12. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
  13. customflush
  14. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-b5a98bbffa0b487589b2a118253f7b62
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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