Potassium Carbonate → (3R,3aR,6R,6aR)-6-((6-chloro-5-(4-phenylpiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

HRID 929249Notes

Reaction equation

HRID 929249 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:11](COCC[Si](C)(C)C)[C:10]([O:20][C@H:21]3[C@H:25]4[O:26][CH2:27][C@@H:28]([OH:29])[C@H:24]4[O:23][CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1I.[C:30]1([CH:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([O:20][C@H:21]3[C@H:25]4[O:26][CH2:27][C@@H:28]([OH:29])[C@H:24]4[O:23][CH2:22]3)=[N:9][C:5]2=[N:6][C:7]=1[N:39]1[CH2:40][CH2:41][CH:36]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:37][CH2:38]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 698734-PhenylpiperidineHCID 145742L-ProlineHCID 90042470(3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol2×

Product 1

HCID 90067338(3R,3aR,6R,6aR)-6-((6-chloro-5-(4-phenylpiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A 2 dram vial was charged with (3R,3aR,6R,6aR)-6-((6-chloro-5-iodo-1-((2-(trimethylsilyl)-ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (Intermediate 3, 300 mg, 0.542 mmol), 4-phenylpiperidine (96 mg, 0.596 mmol), L-proline (12.47 mg, 0.108 mmol), cuprous iodide (10.32 mg, 0.054 mmol), potassium carbonate (150 mg, 1.083 mmol), and DMSO (1354 μl). The reaction vial under nitrogen was placed in a heating block set to 70° C. and then heated to 90° C. for 16 hours. The reaction was cooled to r.t. and diluted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and concentrated. The resulting residue was purified via silica gel chromatography using methanol/dichloromethane to afford the title compound as an orange waxy solid. LC-MS: calculated for C29H39ClN4O5Si 586.24 observed m/e: 587.44 (M+H)+ (Rt 1.41/2 min).

Workup

  1. customThe reaction vial under nitrogen
  2. customset to 70° C.
  3. temperatureThe reaction was cooled to r.t.
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe resulting residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-f8546772c52c42ce82c490a67687ba5f
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…