Methanol → 2-Tert-butyl-4-[(3-methoxypropyl)amino]-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid

HRID 2192839Notes

Reaction equation

HRID 2192839 reaction equation
[C:1]([C:3](=[C:8]([NH:11][C:12](=O)[C:13]([CH3:16])([CH3:15])[CH3:14])SC)[C:4]([O:6]C)=[O:5])#[N:2].C[OH:19].[CH3:20][O:21][CH2:22][CH2:23][CH2:24][NH2:25]>>[C:13]([C:12]1[NH:2][C:1](=[O:19])[C:3]([C:4]([OH:6])=[O:5])=[C:8]([NH:25][CH2:24][CH2:23][CH2:22][O:21][CH3:20])[N:11]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

4

Reactant 3

HCID 887MethanolHCID 16723-MethoxypropylamineHCID 72342760Methyl 2-cyano-3-[(2,2-dimethylpropanoyl)amino]-3-(methylsulfanyl)prop-2-enoate

Product 1

HCID 1361605272-Tert-butyl-4-[(3-methoxypropyl)amino]-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid

Conditions

Temperature
80 °C

Procedure

Methyl 2-cyano-3-[(2,2-dimethylpropanoyl)amino]-3-(methylsulfanyl)prop-2-enoate (2.0 g) was dissolved in 3-methoxypropan-1-amine (1.4 g), and the mixture was stirred at 80° C. for 1 hr. Methanol (10 ml) was added to the reaction mixture, and the mixture was refluxed overnight. The solvent was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography. The fraction eluted with ethyl acetate-hexane (0:10→6:4) was concentrated under reduced pressure, and the fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue (1.0 g) was dissolved in methanol (10 ml), lithium hydroxide (0.42 g) and water (2 ml) were added, and the mixture was stirred at 70° C. for 6 hr. The reaction mixture was allowed to cool to room temperature, acidified with 6 N aqueous hydrochloric acid solution, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object compound (0.51 g).

Workup

  1. temperaturethe mixture was refluxed overnight
  2. concentrationThe solvent was concentrated under reduced pressure
  3. washThe fraction eluted with ethyl acetate-hexane (0:10→6:4)
  4. concentrationwas concentrated under reduced pressure
  5. washthe fraction eluted with ethyl acetate
  6. concentrationwas concentrated under reduced pressure
  7. dissolutionThe residue (1.0 g) was dissolved in methanol (10 ml)
  8. additionlithium hydroxide (0.42 g) and water (2 ml) were added
  9. stirringthe mixture was stirred at 70° C. for 6 hr
  10. temperatureto cool to room temperature
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-2cab7388532e4590a2cfdf3b639657ab
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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