Sodium Carbonate → HCID 123348242, compound

HRID 628426Notes

Reaction equation

HRID 628426 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[C:14]([CH2:19][O:20][Si:21]([C:34]([CH3:37])([CH3:36])[CH3:35])([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:13]=2)[C:9]2[C:4](=[N:5][C:6]([Cl:38])=[CH:7][CH:8]=2)[CH:3]=1.[O:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]1[N:45]1[C:49](B2OC(C)(C)C(C)(C)O2)=[CH:48][CH:47]=[N:46]1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:21]([O:20][CH2:19][C:14]1[CH:13]=[C:12]([CH:17]=[C:16]([Cl:18])[CH:15]=1)[CH2:11][N:10]1[C:9]2[C:4](=[N:5][C:6]([Cl:38])=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:49]1[N:45]([CH:40]2[CH2:41][CH2:42][CH2:43][CH2:44][O:39]2)[N:46]=[CH:47][CH:48]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2×HCID 123485045HCID 123485045, compound

Product 1

HCID 123348242HCID 123348242, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

Tetrakis(triphenylphosphine)palladium(0) (0.65 g, 0.56 mmol, Strem) was added to a degassed mixture of 2-bromo-1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine (3.5 g, 5.6 mmol, from Step 1), 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.5 g, 9.0 mmol, Aldrich) and Na2CO3 (3.0 g, 28 mmol) in 1,2-dimethoxyethane (60 mL) and Water (10 mL). The mixture was heated at reflux for 2 hours. Additional 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.50 g, 1.8 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.32 g, 0.28 mmol) were added, and the reaction mixture was heated at reflux until LCMS indicated that the reaction was complete. After cooling to room temperature, the reaction was diluted with water, and the aqueous mixture was extracted with three portions of EtOAc. The combined organic extracts were washed with water, followed by brine, dried over Na2SO4, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-20% EtOAc in hexanes afforded product as a light yellow oil. Yield: (2.73 g, 70%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 hours
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux until LCMS
  5. extractionthe aqueous mixture was extracted with three portions of EtOAc
  6. washThe combined organic extracts were washed with water
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washFlash chromatography, eluting with a gradient from 0-20% EtOAc in hexanes afforded product as a light yellow oil

Sources & evidence

ORD record
ord-47cff8c8469440cba6f34cb5b061e171
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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