Dimethyl acetylenedicarboxylate → Methyl 5,6-dihydroxy-2-((1-phenylcyclopentyl)methyl)pyrimidine-4-carboxylate

HRID 1409555Notes

Reaction equation

HRID 1409555 reaction equation
[OH-:1].[K+].Cl.[NH2:4]O.[C:6]1([C:12]2([CH2:17][C:18]#[N:19])[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:20]([O:28][CH3:29])(=[O:27])[C:21]#[C:22][C:23](OC)=[O:24]>CO>[CH3:29][O:28][C:20]([C:21]1[N:19]=[C:18]([CH2:17][C:12]2([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:16][CH2:15][CH2:14][CH2:13]2)[NH:4][C:23](=[O:24])[C:22]=1[OH:1])=[O:27]

Participants

6

Reactant 4

HCID 12980Dimethyl acetylenedicarboxylateHCID 14797Potassium HydroxideHCID 223258(1-Phenylcyclopentyl)acetonitrileHCID 443297Hydroxyamine hydrochloride

Product 1

HCID 136377077Methyl 5,6-dihydroxy-2-((1-phenylcyclopentyl)methyl)pyrimidine-4-carboxylateYield 6.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Conditions

Temperature
60 °C

Procedure

A solution of potassium hydroxide (10.8 ml, 10.8 mmol) in methanol and hydroxylamine hydrochloride (10.8 ml, 10.8 mmol) in methanol were mixed, filtered and added to 2-(1-phenylcyclopentyl)acetonitrile (1 g, 5.4 mmol) in methanol (MeOH) and stirred at 60° C. for 24 h. It was then evaporated to dryness. The residue was dissolved in chloroform (30 ml) and to this was added dimethyl but-2-ynedioate (844 mg, 5.94 mmol). The reaction mixture was The mixture was stirred at 60° C. for 24 h, cooled and evaporated to dryness. The residue was dissolved in xylene (10 ml) and heated at 140° C. in a microwave oven for 1 h. The cooled residue was evaporated to dryness. Chromatography was conducted (40 g SiO2; 10 to 70% EtOAc in hexanes). The residue was triturated with EtOAc, filtered and washed with Et2O and dried under vacuum to give the title product as an off-white solid (0.110 g; 6%). LCMS: m/z=329 (MH+).

Workup

  1. filtrationfiltered
  2. customIt was then evaporated to dryness
  3. dissolutionThe residue was dissolved in chloroform (30 ml)
  4. stirringwas stirred at 60° C. for 24 h
  5. temperaturecooled
  6. customevaporated to dryness
  7. dissolutionThe residue was dissolved in xylene (10 ml)
  8. temperatureheated at 140° C. in a microwave oven for 1 h
  9. customThe cooled residue was evaporated to dryness
  10. customThe residue was triturated with EtOAc
  11. filtrationfiltered
  12. washwashed with Et2O
  13. customdried under vacuum

Sources & evidence

ORD record
ord-a77ea70a0282461489f9710ecd3dadfd
Source dataset
uspto-grants-2014_12
Patent number
US08921388B2

Reaction notes

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