Iodine → 3-Imidazo[1,2-a]pyridin-6-ylmethyl-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

HRID 69168Notes

Reaction equation

HRID 69168 reaction equation
II.O[PH2]=O.[N:6]1[CH:7]=[CH:8][N:9]2[CH:14]=[C:13]([CH:15]([C:17]3[N:21]4[N:22]=[C:23]([C:26]5[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=5)[CH:24]=[CH:25][C:20]4=[N:19][CH:18]=3)O)[CH:12]=[CH:11][C:10]=12>C(O)(=O)C.O>[N:6]1[CH:7]=[CH:8][N:9]2[CH:14]=[C:13]([CH2:15][C:17]3[N:21]4[N:22]=[C:23]([C:26]5[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=5)[CH:24]=[CH:25][C:20]4=[N:19][CH:18]=3)[CH:12]=[CH:11][C:10]=12

Participants

6

Reactant 3

HCID 807IodineHCID 4124402Phosphinic AcidHCID 44206290(Rac)-imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-methanol

Product 1

HCID 442062913-Imidazo[1,2-a]pyridin-6-ylmethyl-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

Iodine (50.8 mg, 0.2 mmol) and H3PO2 (0.11 mL of a 50% aqueous solution, 1.0 mmol) were added to a solution of (rac)-Imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-methanol (Example 9, 34.5 mg, 0.1 mmol) in acetic acid (0.5 mL). The RM was heated at 150° C. for 1 h. The RM was diluted with water and extracted with EtOAc. The organic layer was separated and washed with 10% Na2CO3-sol then dried on Na2SO4, filtered and concentrated. Combined aqueous layers were completely neutralized and again extracted with DCM containing little MeOH. Organic layers were evaporated and both crudes from the two extractions were purified together by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5->80:20). The fractions containing the product were evaporated and the residue taken in EtOAc and pentane, filtered and dried under high vacuum to afford the title compound as beige crystals (tR 2.70 min (conditions 3), MH+=330.2, 1H-NMR in DMSO-d6: 8.58 (s, 1H); 8.44 (s, 1H); 8.12 (s, 1H); 8.08 (d, 1H); 7.90 (s, 1H); 7.62 (s, 1H); 7.54-7.44 (m, 3H); 7.22 (d, 1H); 4.31 (s, 2H); 3.90 (s, 3H)).

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with 10% Na2CO3-sol
  4. customthen dried on Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. extractionagain extracted with DCM containing little MeOH
  8. customOrganic layers were evaporated
  9. extractionboth crudes from the two extractions
  10. customwere purified together by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5->80:20)
  11. additionThe fractions containing the product
  12. customwere evaporated
  13. filtrationpentane, filtered
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-5061d117c3bb44788525763270344dba
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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