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

HRID 929255Notes

Reaction equation

HRID 929255 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[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.[S:30]1[CH2:35][CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH2:32][CH2:31]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[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[C:33]1[CH2:34][CH2:35][S:30][CH2:31][CH:32]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 467397352-(3,6-Dihydro-2H-thiopyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2×HCID 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 90041813(3R,3aR,6R,6aR)-6-((6-chloro-5-(3,6-dihydro-2H-thiopyran-4-yl)-1-((2-(trimethylsilyl)-ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Palladium tetrakistriphenylphosphine (41.7 mg, 0.036 mmol) was added to a stirred suspension of (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, 100.0 mg, 0.181 mmol), 2-(3,6-dihydro-2H-thiopyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Intermediate 45, 61.2 mg, 0.270 mmol), and potassium phosphate tribasic (115.0 mg, 0.542 mmol) in degassed 20% water in dioxane (1.85 mL). The reaction mixture placed under N2 and heated at 85° C. for 10 h. The reaction mixture was cooled to room temperature. The lower aqueous layer drawn off and discarded. The remaining reaction mixture was evaporated under reduced pressure. Flash chromatography of the resulting residue utilizing a 12 g silica RediSep Rf® Gold column and employing a 0-100% EtOAc/hexane gradient afforded the title compound. LC-MS: calculated for C23H32ClN3O5SSi 525.15 observed m/e: 526.17 (M+H)+ (Rt 1.64/2.0 min)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe remaining reaction mixture
  3. customwas evaporated under reduced pressure

Sources & evidence

ORD record
ord-0c524c80547947368f0889bfcfed6465
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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