Diisopropyl Ether → HCID 24767994, compound

HRID 1663953Notes

Reaction equation

HRID 1663953 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=O)([CH3:5])[CH3:4])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[CH:23]=[C:24]([CH:41]=[CH:42][C:43]=1[CH3:44])[O:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]3[CH2:40][CH2:39]3)=[O:37])[N:34]=2)[N:31]=1.C(OC(C)C)(C)C>O1CCCC1.CN(C)C=O.Cl.C(OCC)(=O)C>[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:21][C:22]1[CH:23]=[C:24]([O:25][C:26]2[CH:27]=[CH:28][C:29]3[N:30]([CH:32]=[C:33]([NH:35][C:36]([CH:38]4[CH2:39][CH2:40]4)=[O:37])[N:34]=3)[N:31]=2)[CH:41]=[CH:42][C:43]=1[CH3:44])=[O:11])([CH3:4])[CH3:5])#[N:2]

Participants

9

Reactant 4

HCID 7914Diisopropyl EtherHCID 65578Oxalyl chlorideHCID 571495383-(2-Cyanopropan-2-yl)benzoic acidHCID 57505476N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 24767994HCID 24767994, compoundYield 18%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(1-cyano-1-methylethyl)benzoic acid (560 mg, 2.97 mmol) in tetrahydrofuran (15 mL) were added oxalyl chloride (320 μL, 3.71 mmol) and N,N-dimethylformamide (2 drops), and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and the residue was dissolved in N-methylpyrrolidone (15 mL). N-[6-(3-Amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (800 mg, 2.47 mmol) was added to the mixture, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) to give a colorless oil. The oil was dissolved ethyl acetate, and diisopropyl ether was added to allow precipitation to give the title compound (220 mg, 18%) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in N-methylpyrrolidone (15 mL)
  3. stirringthe mixture was stirred at room temperature for 12 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with 5% aqueous sodium hydrogencarbonate solution and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by NH silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)
  10. customto give a colorless oil
  11. additionwas added
  12. customprecipitation

Sources & evidence

ORD record
ord-ba4909a91fe447069f4ab109735314f7
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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