4-Chloro-2-(methylsulfanyl)pyrimidine-5-carbonyl chloride → 1-(4-Chloro-2-(methylthio)pyrimidin-5-yl)-2-(2-chlorophenyl)ethanone

HRID 710594Notes

Reaction equation

HRID 710594 reaction equation
[Cl:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]=[C:4]([S:11][CH3:12])[N:3]=1.[Cl:13][C:14]1[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=1[CH2:16][Mg]Cl>>[Cl:1][C:2]1[C:7]([C:8](=[O:9])[CH2:16][C:15]2[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=2[Cl:13])=[CH:6][N:5]=[C:4]([S:11][CH3:12])[N:3]=1

Participants

3

Reactant 2

HCID 189690784-Chloro-2-(methylsulfanyl)pyrimidine-5-carbonyl chlorideHCID 178478995HCID 178478995, compound

Product 1

HCID 866817731-(4-Chloro-2-(methylthio)pyrimidin-5-yl)-2-(2-chlorophenyl)ethanone

Conditions

Temperature
-78 °C

Procedure

An oven dried flask, equipped with stir bar and septa, was charged with 4-chloro-2-(methylthio)pyrimidine-5-carbonyl chloride (Aaron Chemistry, 1338 mg, 6 mmol). The flask was capped with septa, evacuated and backfilled with nitrogen (three times). The solid was dissolved in tetrahydrofuran (24.0 mL), cooled to −78° C. and kept under nitrogen. (2-Chlorobenzyl)magnesium chloride (14.40 mL, 7.20 mmol) was then slowly added. After the addition was completed, the dry ice/acetone bath was removed and the mixture was stirred at ambient temperature for 3 hours. The mixture was quenched with aqueous 1 M HCl (50 mL), extracted with ethyl acetate (3×80 mL) and the combined extracts were washed with brine, dried over magnesium sulfate (MgSO4), filtered and concentrated. The crude product obtained was purified by flash chromatography (Isco®, Redi-Sep® column, 0-30% ethyl acetate/hexane, linear gradient) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.72 (s, 1H), 7.47-7.36 (m, 1H), 7.36-7.21 (m, 3H), 4.41 (s, 2H), 2.61 (s, 3H); MS (ESI) m/z 313 (M+H)+.

Workup

  1. customAn oven dried flask
  2. customequipped
  3. customThe flask was capped with septa
  4. customevacuated
  5. dissolutionThe solid was dissolved in tetrahydrofuran (24.0 mL)
  6. additionAfter the addition
  7. customthe dry ice/acetone bath was removed
  8. stirringthe mixture was stirred at ambient temperature for 3 hours
  9. customThe mixture was quenched with aqueous 1 M HCl (50 mL)
  10. extractionextracted with ethyl acetate (3×80 mL)
  11. washthe combined extracts were washed with brine
  12. dry with materialdried over magnesium sulfate (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product obtained
  16. customwas purified by flash chromatography (Isco®, Redi-Sep® column, 0-30% ethyl acetate/hexane, linear gradient)

Sources & evidence

ORD record
ord-8a147db3c074423aa7b6384044df7262
Source dataset
uspto-grants-2015_11
Patent number
US09181239B2

Reaction notes

Loading…