Tetrahydrofuran → HCID 59320208, compound

HRID 655296Notes

Reaction equation

HRID 655296 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)=[N:9][N:10]=2)[N:7]=1.O1[CH2:26][CH2:25][CH2:24]C1>C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[CH:24]1([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][C:12]4[CH:13]=[C:14]5[C:19](=[CH:20][CH:21]=4)[N:18]=[CH:17][CH:16]=[CH:15]5)=[N:9][N:10]=3)[N:7]=2)[CH2:25][CH2:26]1

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 249683676-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline

Product 1

HCID 59320208HCID 59320208, compound

Reagents, catalysts & solvents 1

HCID 5483663Ferric acetylacetonateCatalyst

Conditions

Temperature
50 °C

Procedure

A mixture of 6-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (240 mg), iron(III) acetylacetonate (12 mg) in tetrahydrofuran (5 mL) was degassed by bubbling nitrogen through for 10 minutes. The cyclopropyl magnesium bromide in tetrahydrofuran solution prepared in step 1 was then added to the reaction mixture and stirred at 50° C. for 18 hours. The mixture was allowed to cool to rt then acidified to pH 1 via the addition of 1N hydrochloric acid (20 mL). The tetrahydrofuran was removed in vacuo and the aqueous neutralized via the addition of aqueous NaHCO3 and then extracted with ethyl acetate (×3), dried (Na2SO4) and concentrated to dryness. The residue was taken up in piperidine (1 mL) and heated in a microwave at 12° C. for 25 min to consume the remaining 6-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline. The title compound was then purified via preparatory HPLC to return the title compound (4 mg, 10%). Analytical data presented in Table 1.

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through for 10 minutes
  3. additionThe cyclopropyl magnesium bromide in tetrahydrofuran solution prepared in step 1 was then added to the reaction mixture
  4. temperatureto cool to rt
  5. additionthen acidified to pH 1 via the addition of 1N hydrochloric acid (20 mL)
  6. customThe tetrahydrofuran was removed in vacuo
  7. additionthe aqueous neutralized via the addition of aqueous NaHCO3
  8. extractionextracted with ethyl acetate (×3)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated to dryness
  11. temperatureheated in a microwave at 12° C. for 25 min
  12. customto consume the remaining 6-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline
  13. customThe title compound was then purified via preparatory HPLC

Sources & evidence

ORD record
ord-0b699d4277524dbb808114d6e38cb76c
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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