Stannous chloride dihydrate → Tetrahydro-pyran-4-carboxylic acid [7-aminomethyl-6-(2,4-dichloro-phenyl)-imidazo[1,2-a]pyridin-3-yl]-amide

HRID 420532Notes

Reaction equation

HRID 420532 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([C:21]#[N:22])=[CH:11][C:12]2[N:13]([C:15]([N+:18]([O-])=O)=[CH:16][N:17]=2)[CH:14]=1.[OH2:23].[OH2:24].[Sn](Cl)Cl>CCO>[NH2:22][CH2:21][C:10]1[C:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])=[CH:14][N:13]2[C:15]([NH:18][C:9]([CH:3]3[CH2:4][CH2:5][O:24][CH2:7][CH2:2]3)=[O:23])=[CH:16][N:17]=[C:12]2[CH:11]=1

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 666592236-(2,4-Dichloro-phenyl)-3-nitro-imidazo[1,2-a]pyridine-7-carbonitrile

Product 1

HCID 57906482Tetrahydro-pyran-4-carboxylic acid [7-aminomethyl-6-(2,4-dichloro-phenyl)-imidazo[1,2-a]pyridin-3-yl]-amideYield 28%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of the previously obtained 6-(2,4-dichloro-phenyl)-3-nitro-imidazo[1,2-a]pyridine-7-carbonitrile and Tin(II) chloride dihydrate (3.61 g, 15.7 mmol) in absolute EtOH (10 mL) was refluxed for 10 min, then cooled to RT and concentrated under vacuum. The residue was suspended into a 2M NaOH solution in water (100 mL) and extracted with DCM (4×50 mL). The combined organic fractions were washed with brine, dried over Na2SO4, filtered, and evaporated to dryness. The remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH—NH3 99:1→95:5) to yield the title compound (517 mg, 1.71 mmol, 28% for 2 steps). HPLC: AtRet=1.34; TLC: RF 0.47 (DCM/7N NH3 in MeOH 95:5).

Workup

  1. temperaturewas refluxed for 10 min
  2. concentrationconcentrated under vacuum
  3. extractionextracted with DCM (4×50 mL)
  4. washThe combined organic fractions were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH—NH3 99:1→95:5)

Sources & evidence

ORD record
ord-6882ee6ecd744c08862058770b4d4169
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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