Dimethylformamide → HCID 86728279, compound

HRID 1776894Notes

Reaction equation

HRID 1776894 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[CH:17]=2)[C:5](O)=[N:6][CH:7]=1.CN([CH:21]=[O:22])C.O=P(Cl)(Cl)[Cl:25]>>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:17]=2[CH:21]=[O:22])[C:5]([Cl:25])=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 178517590HCID 178517590, compound

Product 1

HCID 86728279HCID 86728279, compoundYield 51%

Conditions

Temperature
100 °C

Procedure

A solution of 5-bromo-3-(imidazo[1,2-a]pyridin-2-yl)pyridin-2-ol (500 mg, 1.72 mmol) in POCl3 (10 mL) was stirred at 100° C. overnight. Then DMF (10 mL) was added dropwise. The reaction mixture was stirred at 100° C. for 3 hours. The reaction mixture was concentrated in vacuo. The resulting residue was suspended with water, and saturated aqueous NaHCO3 solution was added until the solution was at pH 7. The mixture was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified using column chromatography (eluted with dichloromethane:MeOH=50:1) to provide 2-(5-bromo-2-chloropyridin-3-yl)imidazo[1,2-a]pyridine-3-carbaldehyde (300 mg, yield: 51%). 1H-NMR (CDCl3, 400 MHz) δ 9.87 (s, 1H), 9.62 (d, J=7.2 Hz, 1H), 8.61 (d, J=2.4 Hz, 1H), 8.12 (d, J=2.4 Hz, 1H), 7.84 (d, J=9.2 Hz, 1H), 7.63˜7.67 (m, 1H), 7.21˜7.24 (m, 2H). MS (M+H)+: 336/338.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionwas added until the solution
  3. extractionThe mixture was extracted with EtOAc
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified
  9. washcolumn chromatography (eluted with dichloromethane:MeOH=50:1)

Sources & evidence

ORD record
ord-d1c15b9952324feca3fc339b41dd2c68
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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