Nitrogen → (2R,3S,5R)-5-((6-chloro-5-(4-((1-hydroxypropan-2-yl)oxy)phenyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

HRID 1050259Notes

Reaction equation

HRID 1050259 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:19]=[CH:18][C:12]([O:13][CH:14]([CH3:17])[CH2:15][OH:16])=[CH:11][CH:10]=2)O1.[Cl:21][C:22]1[CH:23]=[C:24]2[NH:31][C:30]([O:32][C@H:33]3[CH2:38][O:37][C@H:36]([CH2:39][OH:40])[C@@H:35]([OH:41])[CH2:34]3)=[N:29][C:25]2=[N:26][C:27]=1I.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>O1CCOCC1.O.CCOC(C)=O>[Cl:21][C:22]1[CH:23]=[C:24]2[NH:31][C:30]([O:32][C@H:33]3[CH2:38][O:37][C@H:36]([CH2:39][OH:40])[C@@H:35]([OH:41])[CH2:34]3)=[N:29][C:25]2=[N:26][C:27]=1[C:9]1[CH:10]=[CH:11][C:12]([O:13][CH:14]([CH3:17])[CH2:15][OH:16])=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 90044277(2R,3S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-olHCID 900774282-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-1-ol

Product 1

HCID 73332705(2R,3S,5R)-5-((6-chloro-5-(4-((1-hydroxypropan-2-yl)oxy)phenyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-1-ol (61.3 mg, 0.220 mmol), (2R,3S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (75 mg, 0.176 mmol) and potassium phosphate tribasic (150 mg, 0.70 mmol) were dissolved in dioxane (600 μl) and water (600 μl). The mixture was sparged with N2 with for 15 min and [1,1′-Bis(Diphenyl-phosphino)Ferrocene]Dichloropalladium(II) (25.8 mg, 0.035 mmol) was added. The reaction was stirred 3 h at 80° C., then diluted with water and EtOAc. The aqueous phase was extracted with EtOAc (×2), and the combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by mass directed reverse phase HPLC eluted with acetonitrile in water containing 0.1% formic acid. The desired fractions were combined and lyophilized to give the title compound as a white solid. LC-MS: calculated for C21H24ClN3O6 449.14 observed m/e: 449.92 (M+H)+ (Rt 1.03/2 min); 1H NMR δ (ppm) (CD3OD): 7.77 (s, 1H), 7.58 (d, 2H), 7.02 (d, 2H), 5.10 (septet, 1H), 4.57-4.54 (m, 2H), 4.32 (dd, 1H), 3.88 (d, 1H), 3.73-3.59 (m, 3H), 3.36 (t, 1H), 3.17-3.14 (m, 1H), 2.75-2.73 (m, 1H), 1.67 (dd, 1H), 1.31 (d, 3H).

Workup

  1. additionwas added
  2. extractionThe aqueous phase was extracted with EtOAc (×2)
  3. washthe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by mass
  8. washeluted with acetonitrile in water containing 0.1% formic acid

Sources & evidence

ORD record
ord-fcddbe4452f84096857726a7912c827c
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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