Sodium Hydroxide → (s)-6-Chloro-4-[2-(1-phenylethylamino)pyrimidin-4-yl]-3-(3-trifluoromethyl-phenyl)pyridazine

HRID 394478Notes

Reaction equation

HRID 394478 reaction equation
[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]3[CH:17]=[C:18](O)[N:19]=[N:20][C:21]=3[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].P(Cl)(Cl)([Cl:37])=O>>[Cl:37][C:18]1[N:19]=[N:20][C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)=[C:16]([C:14]2[CH:13]=[CH:12][N:11]=[C:10]([NH:9][C@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH3:8])[N:15]=2)[CH:17]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 178461867HCID 178461867, compound

Product 1

HCID 12070269(s)-6-Chloro-4-[2-(1-phenylethylamino)pyrimidin-4-yl]-3-(3-trifluoromethyl-phenyl)pyridazine

Conditions

Temperature
90 °C

Procedure

Compound 9 (3.5 g, 7.96 mmol) and phosphorus oxychloride (20 mL) were combined under argon then heated at 90° C. for 0.5 h. The solution was cooled and poured onto ice. The resulting suspension was made basic with 2N sodium hydroxide and extracted several times with methylene chloride. The combined organic extracts were washed with brine and dried with anhydrous sodium sulfate. Evaporation of the solvent in vacuo gave an oil which was purified by flash column chromatography (hexane ethyl acetate 80:20) to give Compound 10 as a foam: 2.9 g (6.4 mmol, 80%)

Workup

  1. temperatureThe solution was cooled
  2. additionpoured onto ice
  3. extractionextracted several times with methylene chloride
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. customEvaporation of the solvent in vacuo
  7. customgave an oil which
  8. customwas purified by flash column chromatography (hexane ethyl acetate 80:20)

Sources & evidence

ORD record
ord-bfc8b2b48a31417fbea33204e3c1ac78
Source dataset
uspto-grants-2003_08
Patent number
US06602872B1

Reaction notes

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