Iodide Ion → (Rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline

HRID 1942048Notes

Reaction equation

HRID 1942048 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[C:15]([F:25])=[C:16]4[C:21](=[CH:22][C:23]=3[F:24])[N:20]=[CH:19][CH:18]=[CH:17]4)(O)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[I-].O[PH2]=O>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:14]3[C:15]([F:25])=[C:16]4[C:21](=[CH:22][C:23]=3[F:24])[N:20]=[CH:19][CH:18]=[CH:17]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1

Participants

5

Reactant 3

HCID 30165Iodide IonHCID 4124402Phosphinic AcidHCID 58147518(Rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(5,7-difluoro-quinolin-6-yl)-ethanol

Product 1

HCID 58147541(Rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

(rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(5,7-difluoro-quinolin-6-yl)-ethanol (Intermediate D, 23.2 g, 63.7 mmol was dissolved in acetic acid (317 mL) and introduced in 23 microwave reactor-vials. Iodide (2.11 g×23, 191 mmol), followed by H3PO2 50% (2.28 mL×23, 464 mmol) were then added into each vial. Then they were submitted to microwave irradiations 5 min at 150° C. The combined RMs were concentrated in vacuo and the residue was diluted with water, basified by a 4 M NaOH solution and extracted with EtOAc (3×). The organics were joined and washed with brine, dried over Na2SO4 and the solvent was removed. The residue was triturated with diisopropyl ether. The precipitate formed was filtered off to give a beige solid (tR 3.60 min (conditions 1), tR 9.76/10.87 min (conditions 2), MH+=345, 1H-NMR in DMSO-d6: 8.93 (d, 1H); 8.43 (d, 1H); 8.16 (d, 1H); 7.93 (s, 1H); 7.67 (d, 1H); 7.58 (m, 1H); 7.25 (d, 1H); 5.06 (q, 1H); 1.88 (d, 3H)).

Workup

  1. additionintroduced in 23 microwave reactor-vials
  2. additionwere then added into each vial
  3. customirradiations 5 min
  4. customat 150° C
  5. concentrationThe combined RMs were concentrated in vacuo
  6. additionthe residue was diluted with water
  7. extractionextracted with EtOAc (3×)
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. customthe solvent was removed
  11. customThe residue was triturated with diisopropyl ether
  12. customThe precipitate formed
  13. filtrationwas filtered off
  14. customto give a beige solid (tR 3.60 min (conditions 1)
  15. custom10.87 min (conditions 2), MH+=345, 1H-NMR in DMSO-d6: 8.93 (d, 1H); 8.43 (d, 1H); 8.16 (d, 1H); 7.93 (s, 1H); 7.67 (d, 1H); 7.58 (m, 1H); 7.25 (d, 1H); 5.06 (q, 1H); 1.88 (d, 3H)

Sources & evidence

ORD record
ord-64fb8fc166294945b27a7d6b36a18ca1
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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