2-(Dimethylamino)ethanol → HCID 57690626, compound

HRID 1929391Notes

Reaction equation

HRID 1929391 reaction equation
CN(C)CCO.[Li].[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[N:9]=1.[F:31][C:32]1[N:43]=[CH:42][CH:41]=[CH:40][C:33]=1[C:34](N(OC)C)=[O:35]>C1COCC1>[F:31][C:32]1[N:43]=[CH:42][CH:41]=[CH:40][C:33]=1[C:34]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([N:18]2[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]2)[N:9]=1)=[O:35]

Participants

6

Reactant 4

HCID 79022-(Dimethylamino)ethanolHCID 3028194LithiumHCID 534170672-Fluoro-N-methoxy-N-methylnicotinamideHCID 57690803tert-Butyl 4-(isoquinolin-3-yl)piperazine-1-carboxylate

Product 1

HCID 57690626HCID 57690626, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2-dimethylaminoethanol (0.072 ml, 0.72 mmol) in hexanes (3 ml) was cooled down to −40° C. A 2.5M solution of nbutyl lithium in tetrahydrofuran (0.574 ml, 1.44 mmol) was added dropwise. The solution was stirred for 20 minutes. A suspension of tert-butyl 4-(isoquinolin-3-yl)piperazine-1-carboxylate (0.75 mg, 0.24 mmol) in hexanes (8 ml) was added and the resulting solution was stirred for 1 hour. The solution was cooled down to −78° C. A solution of 2-fluoro-N-methoxy-N-methylnicotinamide (176.3 mg, 0.96 mmol) in THF (40 ml) was added dropwise. The reaction mixture was warmed up to −50° and stirred for 1 hour, then the mixture was stirred at 0° C. for a further 1 hour. The crude mixture was partitioned between water and ethyl acetate. The organic extract was dried over magnesium sulfate, filtered and concentrated under vacuo. The residue was and purified on silica gel by flash column chromatography to give the title compound as a yellow oil (8 mg, 8% yield).

Workup

  1. additionwas added
  2. stirringthe resulting solution was stirred for 1 hour
  3. temperatureThe reaction mixture was warmed up to −50°
  4. stirringstirred for 1 hour
  5. stirringthe mixture was stirred at 0° C. for a further 1 hour
  6. customThe crude mixture was partitioned between water and ethyl acetate
  7. extractionThe organic extract
  8. dry with materialwas dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuo
  11. custompurified on silica gel by flash column chromatography

Sources & evidence

ORD record
ord-7d425bb02f8f425e967bbf68220cfac0
Source dataset
uspto-grants-2012_05
Patent number
US08188071B2

Reaction notes

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