Formaldehyde → HCID 131725928, compound

HRID 2213138Notes

Reaction equation

HRID 2213138 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]2[N:15]([CH:19]=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1.Cl.[CH3:24][NH:25][CH3:26].C=O>CO>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]2[N:15]([C:19]([CH2:24][NH:25][CH3:26])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 10473Dimethylamine, hydrochlorideHCID 70249714HCID 70249714, compound

Product 1

HCID 131725928HCID 131725928, compoundYield 53.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 8-[3-(2,4-dichlorophenyl)propoxy]-2-methylimidazo[1,2-α]pyridine (703 mg, 2 mmol, see example 1), dimethylamine hydrochloride (700 mg, 8.48 mmol) and paraformaldehyde (256 mg, 8.48 mmol) in methanol (5 mL) was refluxed for 40 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between dichloromethane (15 mL) and saturated aq sodium bicarbonate solution (5 mL) and water (5 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×10 mL). The organic extracts were combined, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by dry column (60 mL funnel, silica gel 10–40μl, Sigma cat. S-6628) eluted with increasingly polar mixtures of ethyl acetate-hexanes (v/v: 1:1.4, 1.2:1, 2:1, 2.9:1, 5:1, containing 0.5% v/v isopropylamine) yielded 406 mg (52% yield) of 8-[3-(2,4-dichlorophenyl)propoxy]-3-[(methylamino)methyl]-2-methylimidazo[1,2-α]pyridine in the first fraction (Rf=0.20 in ethyl acetate-hexanes, 2:1 v/v, containing 0.5% v/v isopropylamine) and 221 mg (27% yield) of 8-[3-(2,4-dichlorophenyl)propoxy]-3-[(dimethylamino)methyl]-2-methylimidazo[1,2-α]pyridine in the second fraction (Rf=0.07 in ethyl acetate-hexanes, 2:1 v/v, containing 0.5% v/v isopropylamine).

Workup

  1. temperaturewas refluxed for 40 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was partitioned between dichloromethane (15 mL) and saturated aq sodium bicarbonate solution (5 mL) and water (5 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with dichloromethane (2×10 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification
  9. customby dry column (60 mL funnel, silica gel 10–40μl, Sigma cat. S-6628)
  10. washeluted
  11. temperaturewith increasingly polar mixtures of ethyl acetate-hexanes (v/v
  12. addition1:1.4, 1.2:1, 2:1, 2.9:1, 5:1, containing 0.5% v/v isopropylamine)

Sources & evidence

ORD record
ord-9aaa9eb974214e17b4eed9712857273a
Source dataset
uspto-grants-2006_09
Patent number
US07105534B2

Reaction notes

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