Water → 1-{6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridin-3-yl}-ethanol

HRID 69300Notes

Reaction equation

HRID 69300 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([CH2:16][C:17]4[CH:18]=[CH:19][C:20]5[N:21]([C:23]([C:26](=[O:28])[CH3:27])=[CH:24][N:25]=5)[CH:22]=4)=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1.O.[BH4-].[Na+].O1CCOCC1>CO>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([CH2:16][C:17]4[CH:18]=[CH:19][C:20]5[N:21]([C:23]([CH:26]([OH:28])[CH3:27])=[CH:24][N:25]=5)[CH:22]=4)=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 312751,4-DioxaneHCID 4311764Sodium borohydride2×HCID 57917427HCID 57917427, compound

Product 1

HCID 579172831-{6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridin-3-yl}-ethanol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-{6-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-imidazo[1,2-a]pyridin-3-yl}-ethanone (Example 301, 50 mg, 0.135 mmol) was dissolved in MeOH (3 mL) and water (1 mL) then NaBH4 (3.1 mg, 0.081 mmol) was added. The RM was stirred at rt for 2 h. More equivalents of NaBH4 (3 times 5.1 mg, 0.135 mmol) were added to RM over 18 h. Then dioxane was added and it was stirred at 60° C. for 2 h. It was quenched with EtOAc and solvents were removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt compound of the title compound as a white solid (tR 0.6 min (conditions 2), MH+=374).

Workup

  1. stirringit was stirred at 60° C. for 2 h
  2. customIt was quenched with EtOAc and solvents
  3. customwere removed
  4. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  5. dissolutionThe residue was dissolved in MeOH
  6. customto remove the TFA salt
  7. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-7100ae2075f541b3b8535c56e3af226d
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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