Iodine → 6-{[6-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]methyl}quinoline

HRID 69155Notes

Reaction equation

HRID 69155 reaction equation
II.O[PH2]=O.[CH3:6][N:7]1[CH:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([CH:21]([C:23]4[CH:24]=[C:25]5[C:30](=[CH:31][CH:32]=4)[N:29]=[CH:28][CH:27]=[CH:26]5)O)=[CH:19][N:20]=3)[N:17]=2)[CH:9]=[N:8]1>C(O)(=O)C.O>[CH3:6][N:7]1[CH:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([CH2:21][C:23]4[CH:24]=[C:25]5[C:30](=[CH:31][CH:32]=4)[N:29]=[CH:28][CH:27]=[CH:26]5)=[CH:19][N:20]=3)[N:17]=2)[CH:9]=[N:8]1

Participants

6

Reactant 3

HCID 807IodineHCID 4124402Phosphinic AcidHCID 57917318HCID 57917318, compound

Product 1

HCID 442060636-{[6-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]methyl}quinoline

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

The title compound was synthesized like described in Tetrahedron Letters, 2001, 42, 831-833): iodine (207 mg, 0.82 mmol) and H3PO2 (0.44 mL of a 50% aqueous solution, 4.07 mmol) were added to a solution of (rac)-[6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-quinolin-6-yl-methanol (Example 1, 145 mg, 0.41 mmol) in acetic acid (1 mL). The RM was subjected to MW-irradiation at 150° C. for 30 min. The RM was diluted with water and extracted with EtOAc. The organic layer was separated and washed carefully with sat. K2CO3-sol then dried filtered and concentrated. Purification by HPLC and then liberation of the free base afforded the title compound as a white solid (tR 1.055 min (conditions 1), MH+=341.2, 1H-NMR in DMSO-d6: 8.9 (d, 1H), 8.5 (s, 1H), 8.4 (d, 1H), 8.2 (d, 1H), 8.1 (s, 1H), 8.05 (s, 1H), 8.0 (d, 1H), 7.9 (d, 1H), 7.8 (s, 1H), 7.7 (d, 1H), 7.6 (dd, 1H), 4.6 (s, 2H), 4.0 (s, 3H)).

Workup

  1. customThe title compound was synthesized
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed carefully with sat. K2CO3-sol
  5. customthen dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by HPLC

Sources & evidence

ORD record
ord-39d2cf2abb654c41bbcd5362220a902d
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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