Hydrochloric Acid → HCID 15952760, compound

HRID 1896415Notes

Reaction equation

HRID 1896415 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.Cl[C:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:13]([CH2:20][N:21]3[CH2:25][CH:24]([CH2:26][CH2:27][CH3:28])[CH2:23][C:22]3=[O:29])=[C:14]([C:16]([F:19])([F:18])[F:17])[N:15]=2)[N:12]=1.Cl.C([O-])(O)=O.[Na+]>C1COCC1.C(CC(=O)C)(=O)C.[Fe+3]>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([CH2:20][N:21]4[CH2:25][CH:24]([CH2:26][CH2:27][CH3:28])[CH2:23][C:22]4=[O:29])=[C:14]([C:16]([F:17])([F:19])[F:18])[N:15]=3)[N:12]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 15952659HCID 15952659, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 15952760HCID 15952760, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 22239907HCID 22239907, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Freshly prepared cyclopropyl magnesium bromide (as described in J. Am. Chem. Soc. (2002), 124, 13856-63; with cyclopropylbromide (48 mg, 0.4 mmol, 1.2 eq) and magnesium powder (10 mg) in 5 ml of THF) is added slowly and dropwise to a mixture of 1-{[6-chloro-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one 30 (120 mg, 0.33 mmol) and iron (III) acetylacetone (3 mg, 0.0165 mmol, 0.05 eq) in THF (5 ml) at room temperature. The reaction is kept at room temperature for 16 h, then hydrolyzed (10 ml of 1 N HCl), neutralized with a saturated solution of NaHCO3 until alkaline pH. The crude product is extracted with ethyl acetate (3×20 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by preparative chromatography (CH2Cl2/MeOH/NH4OH: 98/2/0.2 (v/v/v)) to afford 1-{[6-cyclopropyl-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl]methyl}-4-propylpyrrolidin-2-one 40.

Workup

  1. extractionThe crude product is extracted with ethyl acetate (3×20 ml)
  2. dry with materialThe cumulated organic layers are dried over MgSO4
  3. filtrationfiltered
  4. customcondensed under reduced pressure
  5. customThe residue is purified by preparative chromatography (CH2Cl2/MeOH/NH4OH: 98/2/0.2 (v/v/v))

Sources & evidence

ORD record
ord-0951553ec6af4a11ac7be5bea8cff4c5
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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