Hydrogen Peroxide → HCID 178461918, compound

HRID 243419Notes

Reaction equation

HRID 243419 reaction equation
[C:1]1([N:7]2[C:11]3[C:12]([C:16]#[N:17])=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:18]([NH:20][C:21]2[N:29]=[CH:28][N:27]=[C:26]3[C:22]=2[N:23]=[CH:24][NH:25]3)[CH3:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=[O:31].[K+].[K+].OO>CS(C)=O.O>[C:1]1([N:7]2[C:11]3[C:12]([C:16]([NH2:17])=[O:31])=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:18]([NH:20][C:21]2[N:29]=[CH:28][N:27]=[C:26]3[C:22]=2[N:23]=[CH:24][NH:25]3)[CH3:19])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 784Hydrogen Peroxide2×HCID 11430Potassium CarbonateHCID 178461917HCID 178461917, compound

Product 1

HCID 178461918HCID 178461918, compoundYield 121.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

3-Phenyl-2-[(S)-1-(9H-purin-6-ylamino)ethyl]-3H-benzoimidazole-4-carbonitrile (70 mg, 0.18 mmol) was dissolved in DMSO (2 mL) and to this solution was added a solution of K2CO3 (10 mg) in water (0.1 mL). H2O2 (0.2 mL, 30% in water) was added dropwise and the resulting solution stirred for 2 h. Very slow hydrolysis occurred as observed by LCMS. The solution was heated at 60° C. over 2 days with additional aliquots of H2O2 (2×0.2 mL). The cooled mixture was poured onto water. The resulting aqueous solution was passed through an SCX cartridge, the cartridge was washed with water and MeOH and the product eluted with 2M NH3 in MeOH. The product fractions were combined and evaporated and the residue purified by chromatography (Si—PCC, 0-10% 2M methanolic NH3 in DCM). The product fractions were concentrated in vacuo to give white solid. This was triturated in ether, filtered and dried in vacuo to give 311 as a white solid (35 mg, 50%). 1H NMR (DMSO-d6, 400 MHz): δ 8.18-8.00 (2H, m), 7.87-7.77 (1H, m), 7.66 (1H, d, J=7.4 Hz), 7.55-7.27 (6H, m), 7.23-7.13 (2H, m), 6.95 (1H, s), 5.38-5.18 (1H, m), 1.46 (3H, d, J=6.7 Hz). LCMS (Method K): RT 1.99 min; m/z 399 [M+H]+

Workup

  1. customVery slow hydrolysis
  2. additionThe cooled mixture was poured onto water
  3. washthe cartridge was washed with water and MeOH
  4. washthe product eluted with 2M NH3 in MeOH
  5. customevaporated
  6. customthe residue purified by chromatography (Si—PCC, 0-10% 2M methanolic NH3 in DCM)
  7. concentrationThe product fractions were concentrated in vacuo
  8. customto give white solid
  9. customThis was triturated in ether
  10. filtrationfiltered
  11. customdried in vacuo

Sources & evidence

ORD record
ord-24c41f0533e64cafb0034d22dc210a43
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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