Water → HCID 178482332, compound

HRID 1696257Notes

Reaction equation

HRID 1696257 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]2[NH:8][C:9](=[O:18])[N:10]([C@H:11]3[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]3[CH3:17])[C:4]=2[C:3]=1[NH2:19].[CH3:20][N:21]=[C:22]=S.O>C1(C)C(CCO)=CC=CC=1>[CH3:20][NH:21][C:22]1[NH:1][C:2]2=[N:7][CH:6]=[C:5]3[NH:8][C:9](=[O:18])[N:10]([C@H:11]4[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]4[CH3:17])[C:4]3=[C:3]2[N:19]=1

Participants

5

Reactant 3

HCID 962WaterHCID 11167Methyl isothiocyanateHCID 67278322HCID 67278322, compound

Product 1

HCID 178482332HCID 178482332, compound

Reagents, catalysts & solvents 1

HCID 882672-Methylphenethyl alcoholSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 6,7-diamino-1-[(1S,2R)-2-methylcyclohexyl]-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (147 mg) in toluene-ethanol (1 mL-0.5 mL) was added methyl isothiocyanate (43 μL). The resulting solution was heated for 80° C. for 1 hour. After cooling to ambient temperature, the reaction mixture was added drop wise water. The mixture was extracted with EtOAc (2×15 mL). The combined extracts were washed with brine (20 mL), dried over MgSO4. Removal of the solvent preceded the crude thiocarbamate which was used in the next step with out purification. To a solution of above carbamate in toluene (1 mL) was added WSCD HCl (162 mg) at ambient temperature. The mixture was heated at 110° C. for 1 hour. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc (20 mL), and washed with saturated aqueous sodium hydrogencarbonate (20 mL) and brine (20 mL). The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (silica gel chloroform:methanol=90:10) to give 2-(methylamino)-8-[(1S,2R)-2-methylcyclohexyl]-6,8-dihydrodiimidazo[4,5-b:4′,5′-d]pyridin-7(3H)-one (10 mg) as a pale yellow solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionThe mixture was extracted with EtOAc (2×15 mL)
  3. washThe combined extracts were washed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. customRemoval of the solvent
  6. customwas used in the next step with out purification
  7. additionTo a solution of above carbamate in toluene (1 mL) was added WSCD HCl (162 mg) at ambient temperature
  8. temperatureThe mixture was heated at 110° C. for 1 hour
  9. temperatureAfter cooling to ambient temperature
  10. additionthe reaction mixture was diluted with EtOAc (20 mL)
  11. washwashed with saturated aqueous sodium hydrogencarbonate (20 mL) and brine (20 mL)
  12. dry with materialThe organic layer was dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by column chromatography (silica gel chloroform:methanol=90:10)

Sources & evidence

ORD record
ord-0c883951b1f44a64a46b5e004473d46d
Source dataset
uspto-grants-2012_04
Patent number
US08163767B2

Reaction notes

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