1,3-Dichloroacetone → 2-(Chloromethyl)-6-ethoxyimidazo[1,2-a]pyridine

HRID 1416281Notes

Reaction equation

HRID 1416281 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH3:10])=[CH:4][N:3]=1.[Cl:11][CH2:12][C:13]([CH2:15]Cl)=O>C(COC)OC>[Cl:11][CH2:12][C:13]1[N:1]=[C:2]2[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH3:10])=[CH:4][N:3]2[CH:15]=1

Participants

4

Reactant 2

HCID 107931,3-DichloroacetoneHCID 193671035-Ethoxypyridin-2-amine

Product 1

HCID 193671332-(Chloromethyl)-6-ethoxyimidazo[1,2-a]pyridine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-5-ethoxypyridine (1.53 g; prepared by the method of Lombardino, J. Med. Chem. 1981, 24, 39-42), 1,3-dichloroacetone (Aldrich; 1.115 g), and dimethoxyethane (7 mL) is stirred overnight at room temperature. The mixture is concentrated under reduced pressure and ethanol (22.5 mL) is added. After the mixture is stirred for 30 min at 80° C., it is cooled and then concentrated under reduced pressure. The residue is partitioned between dichloromethane and saturated aq. sodium bicarbonate. The combined organic layers are dried with MgSO4 and concentrated under reduced pressure. The residue is chromatographed on silica gel using methanol/dichloromethane (4/96) and crystallized from ether/dichlormethane/hexane to give 0.94 g of 2-(chloromethyl)-6-ethoxyimidazo[1,2-α]pyridine in three crops; mp 95-96° C.; MS m/z 210, 212; IR (mineral oil) 1192, 1263, 810, 1537, 1511 cm-1 ; 1H NMR (CDCl3) δ1.45, 3.97, 4.75, 6.98, 7.46, 7.55, 7.58.

Workup

  1. customprepared by the method of Lombardino, J
  2. concentrationThe mixture is concentrated under reduced pressure and ethanol (22.5 mL)
  3. additionis added
  4. temperatureit is cooled
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is partitioned between dichloromethane and saturated aq. sodium bicarbonate
  7. dry with materialThe combined organic layers are dried with MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is chromatographed on silica gel
  10. customcrystallized from ether/dichlormethane/hexane

Sources & evidence

ORD record
ord-954c830158ee4c8884c0105434ec444f
Source dataset
uspto-grants-1999_06
Patent number
US05912246

Reaction notes

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