Carbon Dioxide → 6-Chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acid

HRID 2239896Notes

Reaction equation

HRID 2239896 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:27])[CH:9]=[C:10]([N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.C([Li])CCC.[C:33](=[O:35])=[O:34]>C1COCC1>[Cl:27][C:8]1[CH:9]=[C:10]([N:11]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5]2[N:6]([C:2]([C:33]([OH:35])=[O:34])=[CH:3][N:4]=2)[N:7]=1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 866117503-bromo-6-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amineHCID 178418339Butyllithium

Product 1

HCID 596248836-Chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acidYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To an oven dried 25 ml shlenk flask under nitrogen was added 3-bromo-6-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine (0.5 g, 1.1 mmol) from Example XXXI step (1a) and THF (5.0 ml). The solution was cooled to −78° C. and n-butyllithium was added drop-wise over 10 minutes. The reaction was allowed to stir at the depressed temperature for 1 hour. Carbon dioxide gas was then introduced via a needle purging the solution for 2 minutes. The reaction was allowed to warm to 25° C. and stir for an additional 30 minutes. Dilute 1N HCl was added taking the aqueous portion to pH=5. Ethyl acetate was added and the layers separated. The organic layer was washed with water (20 ml), then brine (10 ml), dried over Na2SO4, filtered and concentrated to provide 0.47 g of 6-chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acid (98%). m/z=(410, M+1).

Workup

  1. customTo an oven dried 25 ml shlenk flask under nitrogen
  2. custompurging the solution for 2 minutes
  3. temperatureto warm to 25° C.
  4. stirringstir for an additional 30 minutes
  5. additionDilute 1N HCl
  6. additionwas added
  7. additionEthyl acetate was added
  8. customthe layers separated
  9. washThe organic layer was washed with water (20 ml)
  10. dry with materialbrine (10 ml), dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-a6758099ab1b4b89923b161b3f8ec29d
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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