Cyanogen Bromide → HCID 57590545, compound

HRID 1783552Notes

Reaction equation

HRID 1783552 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][CH2:12][C:13]2[C:14]([NH2:21])=[N:15][C:16]([S:19][CH3:20])=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[N:22]#[C:23]Br>CN(C)C=O>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([N:11]2[CH2:12][C:13]3[C:14](=[N:15][C:16]([S:19][CH3:20])=[N:17][CH:18]=3)[N:21]=[C:23]2[NH2:22])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1

Participants

4

Reactant 2

HCID 10476Cyanogen Bromide2×HCID 54105947HCID 54105947, compound

Product 1

HCID 57590545HCID 57590545, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Into a solution of 25.0 g (81.6 mmol) of 5-[(3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-ylamine in 125 mL of dry dimethylformamide cooled to 5° C., was added a solution of 10.1 g (95.5 mmol) of cyanogen bromide in 25 mL of dry dimethylformamide portionwise. After the addition of the cyanogen bromide solution the ice bath was removed, and the reaction was allowed to warm to room temperature over 30 minutes. The reaction was warmed to 80° C. for 4 hours, then added to 500 mL of 1N NaOH. The aqueous suspension was extracted with dichloromethane (7×150 mL). The dichloromethane layers were combined and concentrated in vacuo. The residue was dissolved in dichloromethane, extracted three times with a saturated solution of sodium chloride, dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in tetrahydrofuran, added silica gel, and concentrated in vacuo. The residue was chromatographed down silica gel, eluting first with ethyl acetate, then switching to ethyl acetate/ethanol (9:1 v/v), giving product which was slightly impure. This product was rechromatographed down silica gel, eluting with first chloroform, then switching to chloroform/methanol (9:0.5 v/v), to give 7.34 g (24%) of the title compound: mp 198-204° C.

Workup

  1. customwas removed
  2. temperatureThe reaction was warmed to 80° C. for 4 hours
  3. additionadded to 500 mL of 1N NaOH
  4. extractionThe aqueous suspension was extracted with dichloromethane (7×150 mL)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in dichloromethane
  7. extractionextracted three times with a saturated solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in tetrahydrofuran
  11. additionadded silica gel
  12. concentrationconcentrated in vacuo
  13. customThe residue was chromatographed down silica gel
  14. washeluting first with ethyl acetate
  15. customgiving product which
  16. customThis product was rechromatographed down silica gel
  17. washeluting with first chloroform

Sources & evidence

ORD record
ord-03de9b8b252b48fab13a5348d20f8b57
Source dataset
uspto-grants-2009_03
Patent number
US07501425B1

Reaction notes

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