Potassium Phosphate, Tribasic → HCID 90042093, compound

HRID 929178Notes

Reaction equation

HRID 929178 reaction equation
[CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9](I)=[C:10]([Cl:13])[CH:11]=2)[N:6]=[C:5]1[O:15][C@@H:16]1[CH2:20][O:19][C@@H:18]2[C@H:21]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:22][O:23][C@H:17]12)[CH:2]=[CH2:3].CC1(C)C(C)(C)OB([C:40]2[CH:45]=[CH:44][C:43]([N:46]3[CH2:50][CH2:49][CH2:48][CH2:47]3)=[CH:42][CH:41]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl>[CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9]([C:40]3[CH:41]=[CH:42][C:43]([N:46]4[CH2:47][CH2:48][CH2:49][CH2:50]4)=[CH:44][CH:45]=3)=[C:10]([Cl:13])[CH:11]=2)[N:6]=[C:5]1[O:15][C@@H:16]1[CH2:20][O:19][C@@H:18]2[C@H:21]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:22][O:23][C@H:17]12)[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 185257151-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidineHCID 123197088HCID 123197088, compound

Product 1

HCID 90042093HCID 90042093, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichlormethane complex (17.1 mg, 0.021 mmol) was added to a stirred suspension of [(3R,3aR,6R,6aS)-3-(1-allyl-6-chloro-5-iodo-imidazo[4,5-b]pyridin-2-yl)oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane (99.8 mg, 0.173 mmol), 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrrolidine (59.6 mg, 0.218 mmol), and tripotassium phosphate (225.0 mg, 1.060 mmol) in dioxane (1.38 ml) and water (0.35 ml). The reaction mixture was degassed (3×) and placed under nitrogen before being heated to 80° C. After 15 hours, the reaction mixture was cooled to room temperature. 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, washed with brine, dried over MgSO4, filtered, and evaporated under reduced pressure to give an amber residue. This residue was dissolved in DCM, loaded onto a 5 g silica solid load cartridge and purified using an ISCO Rf and a 4 g silica column (CV=4.8 ml). The column was eluted as follows: 100% hexane (5 CV), 0-30% EtOAc/hexane gradient (70 CV), 30% EtOAc/hexane (21 CV) at 18 ml/min. The product fractions were combined and evaporated under reduced pressure to give the title compound as a yellow residue. LC-MS: calculated for C31H41ClN4O4Si 596.26 observed m/e: 597.39 (M+H)+ (Rt 1.34/2 min).

Workup

  1. customThe reaction mixture was degassed (3×)
  2. temperaturethe reaction mixture was cooled to room temperature
  3. customThe reaction mixture was partitioned between EtOAc (40 ml) and water (40 ml)
  4. extractionThe aqueous layer was extracted with EtOAc (2×20 ml)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give an amber residue
  10. custompurified
  11. washThe column was eluted
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-01d0c0a422784dc58f7026f55aea4692
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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