Methyl isothiocyanate → HCID 178482303, compound

HRID 1890907Notes

Reaction equation

HRID 1890907 reaction equation
[N:1]([CH3:4])=[C:2]=S.[Br:5][C:6]1[CH:11]=[C:10]([NH2:12])[C:9]([NH2:13])=[C:8]([CH3:14])[CH:7]=1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.CO>[Br:5][C:6]1[CH:7]=[C:8]([CH3:14])[C:9]2[NH:13][C:2]([NH:1][CH3:4])=[N:12][C:10]=2[CH:11]=1

Participants

6

Reactant 3

HCID 11167Methyl isothiocyanateHCID 15163975-Bromo-3-methylbenzene-1,2-diamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 178482303HCID 178482303, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

Isothiocyanatomethane (0.055 g, 0.746 mmol) in N,N-dimethylformamide (1.0 mL) was added dropwise slowly to a stirred solution of 5-bromo-3-methylbenzene-1,2-diamine (0.150 g, 0.746 mmol) in N,N-dimethylformamide (1.5 mL) at 0° C. The cold bath was removed, the reaction mixture was capped and stirred at room temperature for 48 h. N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.157 g, 0.821 mmol) was added and the reaction mixture capped and heated at 40° C. overnight. The resulting mixture was diluted with methanol, filtered and purified using reverse-phase preparatory HPLC (10-50% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). Fractions containing the desired product were combined and most of the solvent removed under reduced pressure. Acetonitrile was added and the resulting mixture loaded on a Strata ion exchange column. The column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol. The product eluted with the 5% ammonium hydroxide in methanol and was concentrated under reduced pressure and dried under high vacuum to give the desired product (0.128 g, 0.53 mmol, 72% yield) as a slightly yellow waxy solid. MS (ESI) m/z 240 [M]+, 242 [M+2]+.

Workup

  1. customThe cold bath was removed
  2. customthe reaction mixture was capped
  3. customthe reaction mixture capped
  4. temperatureheated at 40° C. overnight
  5. filtrationfiltered
  6. custompurified
  7. customreverse-phase preparatory HPLC (10-50% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  8. additionFractions containing the desired product
  9. customremoved under reduced pressure
  10. additionAcetonitrile was added
  11. washThe column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol
  12. washThe product eluted with the 5% ammonium hydroxide in methanol
  13. concentrationwas concentrated under reduced pressure
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-bfe939efc2854e739d2bcd544d9f9994
Source dataset
uspto-grants-2013_08
Patent number
US08507492B2

Reaction notes

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