Potassium Phosphate, Tribasic → 2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-5-(4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-imidazo[4,5-b]pyridine

HRID 929246Notes

Reaction equation

HRID 929246 reaction equation
[Si:1]([O:8][C@H:9]1[C@H:13]2[O:14][CH2:15][C@@H:16]([O:17][C:18]3[N:19]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:20]4[C:21]([N:42]=3)=[N:22][C:23]([C:27]3[CH:32]=[CH:31][C:30](B5OC(C)(C)C(C)(C)O5)=[CH:29][CH:28]=3)=[C:24]([Cl:26])[CH:25]=4)[C@H:12]2[O:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)S(O[C:57]1[CH2:58][CH2:59][S:60][CH2:61][CH:62]=1)(=O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(=O)(O)[O-].[Na+]>O1CCOCC1.C(=O)=O.CC(C)=O>[Si:1]([O:8][C@H:9]1[C@H:13]2[O:14][CH2:15][C@@H:16]([O:17][C:18]3[N:19]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:48])([CH3:50])[CH3:49])[C:20]4[C:21]([N:42]=3)=[N:22][C:23]([C:27]3[CH:28]=[CH:29][C:30]([C:57]5[CH2:62][CH2:61][S:60][CH2:59][CH:58]=5)=[CH:31][CH:32]=3)=[C:24]([Cl:26])[CH:25]=4)[C@H:12]2[O:11][CH2:10]1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 226257513,6-Dihydro-2H-thiopyran-4-yl trifluoromethanesulfonateHCID 895658652-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)-oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine

Product 1

HCID 900429142-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-5-(4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 18522661Acetone cardiceSolvent

Conditions

Temperature
80 °C

Procedure

Placed 2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)-oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (500 mg, 0.672 mmol), 3,6-dihydro-2H-thiopyran-4-yl trifluoromethanesulfonate (250 mg, 10.8 mmol), and 1M aqueous potassium phosphate tribasic (2.02 ml, 2.02 mmol) under nitrogen in dioxane (7.0 ml). Cooled in dry-ice/acetone bath, pulled a hard vacuum, then introduced nitrogen (3×). Added [1,1′-bis(diphyenylphosphino)ferrocene]dichloropalladium(II) (55 mg, 0.067 mmol) to the frozen mixture, pulled a hard vacuum, then introduced nitrogen (3×). Removed ice bath and stirred mixture at 80° C. for 6 hours. The mixture was cooled to room temperature and poured into saturated aqueous sodium bicarbonate (50 ml). The mixture was extracted with ethyl acetate (2×100 ml), dried over sodium sulfate, and concentrated under reduced pressure. The resultant dark oil was chromatographed using a 40 g silica gel cartridge eluted with 0-40% EtOAc in hexanes over 20 column volumes. The desired product fractions were combined and concentrated under reduced pressure to provide the desired product as a white solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×100 ml)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resultant dark oil was chromatographed
  6. washeluted with 0-40% EtOAc in hexanes over 20 column volumes
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-28fa7ec2479d44209f8125038277b9e3
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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