Potassium Hydroxide → HCID 178508786, compound

HRID 2365478Notes

Reaction equation

HRID 2365478 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C@@H:11]2[CH2:15][NH:14]/[C:13](=[N:16]\[C:17]([C:19]3[C:24]([NH2:25])=[N:23][C:22]([NH2:26])=[C:21]([Cl:27])[N:20]=3)=[O:18])/[NH:12]2)=[CH:4][CH:3]=1.[OH-:28].[K+]>O1CCOCC1.CCOC(C)=O.CO>[OH:28][C@@H:3]([CH2:2][OH:1])[CH2:4][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C@@H:11]2[CH2:15][NH:14]/[C:13](=[N:16]/[C:17]([C:19]3[C:24]([NH2:25])=[N:23][C:22]([NH2:26])=[C:21]([Cl:27])[N:20]=3)=[O:18])/[NH:12]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 178508784HCID 178508784, compound

Product 1

HCID 178508786HCID 178508786, compound

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [(R)-4-[3-(4-hydroxy-phenyl)-propyl]-imidazolidin-(2E)-ylidene]-amide (Ex. 17) (1.0 g, 2.57 mmol) in 1,4 dioxane (38 ml) at 50° C. is added in one portion 0.5 M KOH (5.3 ml, 2.7 mmol) followed by (S)-(−)-Glycidiol (0.170 ml, 2.57 mmol). The resulting mixture is heated at 50° C. for 18 hours and then further (S)-(−)-Glycidiol (0.07 ml, 1.05 mmol) is added in one portion. The resulting mixture is heated at 50° C. for 60 hours and then allowed to cool to room temperature. The solvent is removed in vacuo to afford an orange oil which is dissolved in EtOAc/MeOH 9:1 (100 ml) and washed with 1 M NaOH (50 ml). The organic layer is dried over Na2SO4 and the solvent is removed in vacuo to afford a brown/orange foam. Purification by chromatography (SiO2, DCM/MeOH/NH3) affords the title compound as a yellow foam; [M+H]+ 464; 1H NMR MHz, DMSO-d6): 1.65-1.40 (m, 4H), 2.52 (m, 2H), 3.13 (dd, J=9.6, 7.1 Hz, 1H), 3.42 (br d, J=4.7 Hz, 2H), 3.62 (dd, J=9.6, 9.6 Hz, 1H), 3.76 (m, 1H), 3.78 (m, 1H), 3.80 (m, 1H), 3.94 (dd, J=9.5, 4.0 Hz, 1H), 4.62 (br s, 1H), 4.89 (br s, 1H), 6.68 (br s, 2H), 6.82 (d, J=8.5 Hz, 2H), 7.09 (d, J=8.5 Hz, 2H), 7.2-6.0 (br s, 1H), 8.18 (br s, 1H), 9.3-7.5 (br s, 1H),

Workup

  1. additionfurther (S)-(−)-Glycidiol (0.07 ml, 1.05 mmol) is added in one portion
  2. temperatureThe resulting mixture is heated at 50° C. for 60 hours
  3. temperatureto cool to room temperature
  4. customThe solvent is removed in vacuo
  5. customto afford an orange oil which
  6. washwashed with 1 M NaOH (50 ml)
  7. dry with materialThe organic layer is dried over Na2SO4
  8. customthe solvent is removed in vacuo
  9. customto afford a brown/orange foam
  10. customPurification by chromatography (SiO2, DCM/MeOH/NH3)

Sources & evidence

ORD record
ord-2c716e68c15f44d7b3bec28fc4dfeff5
Source dataset
uspto-grants-2014_04
Patent number
US08697687B2

Reaction notes

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