Propanoic acid, 2-bromo-2-methyl-, ethyl ester → HCID 23000312, compound

HRID 397581Notes

Reaction equation

HRID 397581 reaction equation
[C:1]1([CH:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25](=[O:28])[NH:26][N:27]=4)[N:24]=3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[C:38]([CH3:45])([CH3:44])[C:39]([O:41][CH2:42][CH3:43])=[O:40]>CN(C)C=O>[C:29]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[O:8][CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25](=[O:28])[N:26]([C:38]([CH3:45])([CH3:44])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[N:27]=4)[N:24]=3)[CH2:13][CH2:14]2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl ester2×HCID 24758Sodium hydride2×HCID 9933860HCID 9933860, compound

Product 1

HCID 23000312HCID 23000312, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.606 g of 6-[3-[4-(diphenylmethoxy)piperidino]propylamino][1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one was suspended in 3 ml of N,N-dimethylformamide; 0.063 g of 60% oily sodium hydride was added,-followed by stirring at room temperature for 1 hour. 0.253 ml of ethyl 2-bromoisobutyrate was added, followed by stirring in an oil bath (bath temperature 80° C.) for 17 hours. After cooling, 0.063 g of 60% oily sodium hydride and 0.253 ml of ethyl 2-bromoisobutyrate were added, followed by stirring in an oil bath (bath temperature 80° C.) for 3 hours. After cooling, ice water was added; the reaction mixture was extracted with ethyl acetate; the extract was washed with saturated saline and dried over magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography and eluted with ethyl acetate-methanol-triethylamine (90:10:1). The desired fraction was collected and concentrated to yield 0.38 g of ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-3-oxo[1,2,4]triazolo[4,3-b]pyridazin-2(3H)-yl]-2-methylpropionate as an oily substance. This oily substance was dissolved in 5 ml of ethyl acetate; 0.5 ml of a 4 N solution of hydrogen chloride in ethyl acetate was added, followed by concentration; the residue was powdered from diethyl ether, collected by filtration, and dried, to yield 0.342 g of the title compound.

Workup

  1. stirringby stirring in an oil bath (bath temperature 80° C.) for 17 hours
  2. temperatureAfter cooling
  3. stirringby stirring in an oil bath (bath temperature 80° C.) for 3 hours
  4. temperatureAfter cooling
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. washthe extract was washed with saturated saline
  7. dry with materialdried over magnesium sulfate
  8. concentrationAfter concentration under reduced pressure
  9. washeluted with ethyl acetate-methanol-triethylamine (90:10:1)
  10. customThe desired fraction was collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-20f85a2887aa4563a8703435acc8cf2d
Source dataset
uspto-grants-2003_08
Patent number
US06610694B1

Reaction notes

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