Dichloromethane → HCID 24855564, compound

HRID 912707Notes

Reaction equation

HRID 912707 reaction equation
[CH2:1]([O:5][C:6]1[C:7]([CH2:12][NH:13][C:14]2[N:15]=[CH:16][NH:17][C:18]=2[C:19]([NH2:21])=[O:20])=[N:8][CH:9]=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH3:4].ClCCl.C(OC(N=[C:31]=[S:32])=O)C.FC(F)(F)C(O)=O>C(O)C>[CH2:1]([O:5][C:6]1[C:7]([CH2:12][N:13]2[C:14]3[N:15]=[CH:16][NH:17][C:18]=3[C:19](=[O:20])[NH:21][C:31]2=[S:32])=[N:8][CH:9]=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 85320Ethyl isothiocyanatoformate3×HCID 67416375HCID 67416375, compound

Product 1

HCID 24855564HCID 24855564, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 4-{[(3-butoxypyridin-2-yl)methyl]amino}-1H-imidazole-5-carboxamide (0.991 g, 3.43 mmol, obtained from Example 19(b)) was added dichloromethane (20 mL), ethoxycarbonyl isothiocyanate (0.47 mL, 4.11 mmol) and absolute ethanol (2 mL). After stirring o.n., more ethoxycarbonyl isothiocyanate (0.23 mL) was added and the solution was heated to reflux for 2 h upon, which more ethoxycarbonyl isothiocyanate (0.10 mL) was added and the solution was refluxed for 2 h more. The volatiles were removed in vacuo and 1 N sodium hydroxide (20 mL) was added and the suspension was heated to reflux for 4 h. After cooling to r.t. the solution was neutralized with 2 N hydrochloric acid. The resulting precipitate was filtered, washed with water and dried resulting in 0.699 g of crude product. Purification was achieved with a portion of the crude material (300 mg) by trituration with methanol and dichloromethane and then concentrating the organic layer followed by prep HPLC providing 0.103 g (16% yield, 0.231 mmol) of the title compound as its trifluoroacetic acid salt.

Workup

  1. temperaturethe solution was heated
  2. additionwas added
  3. temperaturethe solution was refluxed for 2 h more
  4. customThe volatiles were removed in vacuo and 1 N sodium hydroxide (20 mL)
  5. additionwas added
  6. temperaturethe suspension was heated
  7. temperatureto reflux for 4 h
  8. filtrationThe resulting precipitate was filtered
  9. washwashed with water
  10. customdried
  11. customresulting in 0.699 g of crude product
  12. customPurification
  13. concentrationconcentrating the organic layer

Sources & evidence

ORD record
ord-0f67bdefe3e24548847ec75e42efedbb
Source dataset
uspto-grants-2011_09
Patent number
US08026244B2

Reaction notes

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