Sodium hydride → HCID 178467428, compound

HRID 81285Notes

Reaction equation

HRID 81285 reaction equation
[CH:1]1([CH:5]([OH:7])[CH3:6])[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:11]1[C:16]2[N:17]([CH2:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]3)[CH:18]=[N:19][C:15]=2[CH:14]=[C:13]([Cl:28])[N:12]=1>CN(C=O)C>[Cl:28][C:13]1[N:12]=[C:11]([O:7][CH:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)[CH3:6])[C:16]2[N:17]([CH2:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]3)[CH:18]=[N:19][C:15]=2[CH:14]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1422621-Cyclobutylethan-1-olHCID 178461251HCID 178461251, compound

Product 1

HCID 178467428HCID 178467428, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 1-cyclobutylethan-1-ol (1.76 g, 17.60 mmol) in DMF (10 mL) was added 60% NaH (1.4 g, 35.19 mmol) in several portions at 0° C. After stirring for 20 minutes, 4,6-dichloro-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine (Preparative Example 2.3, 3.5 g, 11.73 mmol) in DMF (30 mL) was added slowly over a time period of 10 minutes. The reaction was then warmed to room temperature and stirred for 16 h. After this time, the reaction was quenched with ice, diluted with water (80 mL), and extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water (25 mL) and brine (25 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with (12-15% EtOAc/petroleum ether) to yield 6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine. MS ES/APCl calc'd. for C20H28ClN3O [M+H]+ 362. found 362.

Workup

  1. stirringstirred for 16 h
  2. customAfter this time, the reaction was quenched with ice
  3. additiondiluted with water (80 mL)
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. washThe combined organic extracts were washed with water (25 mL) and brine (25 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (
  10. washeluting with (12-15% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-dc6fc12eb4bc4b569c675bdd37c303ca
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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