N-Acetyl-L-Cysteine → 2-(Pyrimidin-2-yl)pyrimidine-5-carboxylic acid

HRID 2382031Notes

Reaction equation

HRID 2382031 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:2].C([NH:12][C@H](C(O)=O)CS)(=O)C.C([O-])(=O)C.[NH4+].C([O:26][C:27]([C:29]([C:32](=O)C)=[CH:30][O-])=[O:28])C.[Na+].[OH-].[Na+]>O.CO>[N:2]1[CH:30]=[C:29]([C:27]([OH:26])=[O:28])[CH:32]=[N:12][C:1]=1[C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

8

Reactant 5

HCID 12035N-Acetyl-L-CysteineHCID 14798Sodium HydroxideHCID 517165Ammonium AcetateHCID 27579792-CyanopyrimidineHCID 86639377Sodium 2-ethoxycarbonyl-3-oxo-but-1-en-1-olate

Product 1

HCID 533964792-(Pyrimidin-2-yl)pyrimidine-5-carboxylic acidYield 59%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A pressure vessel is charged with 2-cyanopyrimidine (7.88 g, 75 mmol), N-acetyl cysteine (1.22 g, 7.5 mmol), ammonium acetate (6.93 g, 90 mmol), and MeOH (75 mL). The vessel is sealed and heated at 110° C. for 1.5 h, and then cooled to rt. To the reaction mixture is added sodium 2-ethoxycarbonyl-3-oxo-but-1-en-1-olate (17 g, 86.25 mmol) and MeOH (75 mL). The mixture is heated to reflux for 1.5 h and then cooled to rt. NaOH (6 g, 150 mmol) and water (80 mL) are added. The mixture is stirred for 30 min or until LC-MS indicates complete hydrolysis of the intermediate ester. The pH of the reaction mixture is adjusted to 3 with concentrated (12 M) aqueous HCl. MeOH is evaporated in vacuo, and the resulting precipitate is collected via filtration and washed with minimal chilled water to yield [2,2′]bipyrimidinyl-5-carboxylic acid (59%). MS: 203 (M+H); 1H NMR (300 MHz, CDCl3): δ=7.71 (t, 1H), 9.06 (d, 2H), 9.40 (s, 2H).

Workup

  1. customThe vessel is sealed
  2. temperaturecooled to rt
  3. temperatureThe mixture is heated
  4. temperatureto reflux for 1.5 h
  5. temperaturecooled to rt
  6. concentrationwith concentrated (12 M) aqueous HCl
  7. customMeOH is evaporated in vacuo
  8. filtrationthe resulting precipitate is collected via filtration
  9. washwashed
  10. temperaturewith minimal chilled water

Sources & evidence

ORD record
ord-aed5129288cf4791beb75f681a9aba11
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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