Iodine → 6-(1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)ethyl)-7-fluoroquinoline

HRID 69268Notes

Reaction equation

HRID 69268 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[CH:15]=[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.II.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[CH:15]=[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 807IodineHCID 4124402Phosphinic AcidHCID 581475421-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoroquinolin-6-yl)ethanol

Product 1

HCID 581475216-(1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)ethyl)-7-fluoroquinoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
150 °C

Procedure

To a solution of (rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoro-quinolin-6-yl)ethanol (Stage 174.1, 200 mg, 0.584 mmol) in acetic acid (3.2 mL) were added iodine (296 mg, 1.167 mmol) and H3PO2 (0.642 mL of a 50% aqueous solution, 5.84 mmol). The RM was heated at 150° C. for 30 min. After cooling down to rt the acetic acid was evaporated under reduced pressure, water was added and the solution was neutralized with a solution of 10% NaHCO3. The product which precipitated was extracted with DCM, the combined organic phase were dried over MgSO4, filtered, evaporated to dryness and the residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, hexane/EtOAc=50:50->0:100) to afford the title compound as a off white crystalline solid (tR 4.61 min (conditions 3), MH+=327.2, 1H-NMR in DMSO-d6: 8.85 (dd, 1H); 8.28 (dd, 1H); 8.20 (d, 1H); 7.85 (s, 1H); 7.78-7.68 (2H, m); 7.44 (dd, 1H); 7.29 (d, 1H); 4.95 (q, 1H); 1.79 (d, 3H)).

Workup

  1. customwas evaporated under reduced pressure, water
  2. additionwas added
  3. customThe product which precipitated
  4. extractionwas extracted with DCM
  5. dry with materialthe combined organic phase were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customthe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, hexane/EtOAc=50:50->0:100)

Sources & evidence

ORD record
ord-2255d85a9ab94dbd9eb8ddb70a5456ba
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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