Water → HCID 178460611, compound

HRID 81238

Reaction equation

HRID 81238 reaction equation
Br[C:2]1[N:19]([CH2:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]2)[C:5]2[C:6]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1.[C:28]([Si:32]([CH3:47])([CH3:46])[O:33][CH2:34][C:35](B1OC(C)(C)C(C)(C)O1)=[CH2:36])([CH3:31])([CH3:30])[CH3:29].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Si:32]([O:33][CH2:34][C:35]([C:2]1[N:19]([CH2:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]2)[C:5]2[C:6]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1)=[CH2:36])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 16069431tert-Butyl(dimethyl){[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-en-1-yl]oxy}silaneHCID 178461197HCID 178461197, compound

Product 1

HCID 178460611HCID 178460611, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1; 3.0 g, 6.93 mmol) in 1,4-dioxane (60 mL), tert-butyldimethyl((2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)oxy)silane (3.09 g 10.39 mmol), potassium phosphate (2.94 g, 13.86 mmol), and water (6 mL) were added, and the mixture was degassed with argon for 15 minutes. PdCl2(dppf) (0.85 g, 1.04 mmol), was added, and the mixture was degassed with argon again for 5 minutes. The reaction was then heated at 100° C. for 16 h. The reaction mixture was cooled to room temperature, quenched with water (20 mL), and extracted with ethyl acetate (100 mL). The organic layer was separated, washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using 15% ethyl acetate/petroleum ether as eluent to yield 2-(3-{[tert-butyl(dimethyl)silyl]oxy}prop-1-en-2-yl)-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calcd. for C29H38ClN5OSi [M+H]+ 536. found 536.

Workup

  1. customthe mixture was degassed with argon for 15 minutes
  2. customthe mixture was degassed with argon again for 5 minutes
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customquenched with water (20 mL)
  5. extractionextracted with ethyl acetate (100 mL)
  6. customThe organic layer was separated
  7. washwashed with brine (50 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ce03b5471c724fc0a624e97fb85cfb55
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Linked notes

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