1,2-Dimethoxyethane → 1-{4-amino-7-[5-(tert-butyldimethylsilanyloxymethyl)pyridin-3-yl]-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

HRID 598023Notes

Reaction equation

HRID 598023 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[Si:25]([O:32][CH2:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[N:38][CH:39]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([C:36]3[CH:37]=[N:38][CH:39]=[C:34]([CH2:33][O:32][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:26])[CH3:27])[CH:35]=3)=[CH:5][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 21984252(5-(((tert-Butyldimethylsilyl)oxy)methyl)pyridin-3-yl)boronic acidHCID 589706811-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

Product 1

HCID 1317287181-{4-amino-7-[5-(tert-butyldimethylsilanyloxymethyl)pyridin-3-yl]-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-olYield 67.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (1.5 g, 3.80 mmol), 5-(tert-butyldimethylsilanyloxymethyl)pyridine-3-boronic acid (1.22 g, 4.57 mmol), potassium carbonate (1.74 g, 12.6 mmol), dichlorobis(triphenylphosphine)palladium(II)(0.027 g, 0.038 mmol), DME (13 mL), and water (7 mL) was stirred under a nitrogen atmosphere and then heated at 110° C. in a pressure vessel for 6 hours and allowed to cool to room temperature. An analysis by LC/MS indicated the reaction was incomplete, and additional dichlorobis(triphenylphosphine)palladium(II)(0.035 g) was added. The reaction was heated at 110 C for 16 hours and allowed to cool to room temperature. The DME was removed under reduced pressure, and the resulting mixture was extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting brown solid was dissolved in dichloromethane (15 mL) purified by chromatography according to the method described in Example 62 to provide 1.37 g of 1-{4-amino-7-[5-(tert-butyldimethylsilanyloxymethyl)pyridin-3-yl]-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a yellow solid.

Workup

  1. temperatureto cool to room temperature
  2. temperatureThe reaction was heated at 110 C for 16 hours
  3. temperatureto cool to room temperature
  4. customThe DME was removed under reduced pressure
  5. extractionthe resulting mixture was extracted with dichloromethane (3×25 mL)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe resulting brown solid was dissolved in dichloromethane (15 mL)
  10. custompurified by chromatography

Sources & evidence

ORD record
ord-9959b0341b814fa5bf0151f0f2dfcdad
Source dataset
uspto-grants-2011_03
Patent number
US07897609B2

Reaction notes

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