Hydrochloric Acid → 4-Methyl-2-(pyrimidin-2-yl)pyrimidine-5-carboxylic acid

HRID 2382026Notes

Reaction equation

HRID 2382026 reaction equation
C([C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1)#N.C([O-])(=O)C.[NH4+].C([NH:17][C@H](C(O)=O)CS)(=O)C.CC(C)([O-])C.[Na+].C([O:32][C:33](=[O:42])[C:34](=[CH:38][N:39]([CH3:41])C)[C:35](=O)[CH3:36])C.[OH-].[Na+].Cl>O.C(O)C>[CH3:36][C:35]1[C:34]([C:33]([OH:32])=[O:42])=[CH:38][N:39]=[C:41]([C:3]2[N:8]=[CH:7][CH:6]=[CH:5][N:4]=2)[N:17]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 12035N-Acetyl-L-CysteineHCID 14798Sodium HydroxideHCID 517165Ammonium AcetateHCID 27579792-CyanopyrimidineHCID 3806790Ethyl 2-acetyl-3-(dimethylamino)acrylateHCID 23676156Sodium t-butoxide

Product 1

HCID 616999854-Methyl-2-(pyrimidin-2-yl)pyrimidine-5-carboxylic acidYield 85%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Procedure

A flask containing 2-cyanopyrimidine (16.6 g, 158 mmol), ammonium acetate (14.6 g, 189.6 mmol) and N-acetylcysteine (2.58 g, 15.8 mmol) and ethanol (160 mL) is heated to reflux. After 1.25 h, the reaction is allowed to cool slightly (to approximately 50° C.), and sodium tert-butoxide (15.18 g, 158 mmol) and ethanol (160 mL) are added. After stirring for 10 minutes, 2-dimethylaminomethylene-3-oxo-butyric acid ethyl ester (33.6 g, 181.7 mmol) is added. The reaction is then heated to reflux for an additional 2 h. The reaction is then allowed to cool to rt, and sodium hydroxide (12.6 g, 316 mmol) in water (50 mL) is added. After 2 h, the reaction is chilled in an ice water bath and the reaction pH is adjusted to 3 using a solution of 12M aqueous HCl. The reaction mixture is then reduced in vacuo to 100 mL. Additional water (100 mL) is added and the suspension is chilled in an ice water bath, filtered and the solids are washed with minimal chilled water. The solids are then dried in vacuo to afford 4-methyl-[2,2′]bipyrimidinyl-5-carboxylic acid (85%). MS: 217 (M+H); 1H NMR (300 MHz, CDCl3): δ=2.80 (s, 3H), 7.66 (t, 1H), 9.01 (d, 2H), 9.14 (s, 1H).

Workup

  1. temperatureis heated to reflux
  2. additionare added
  3. temperatureThe reaction is then heated
  4. temperatureto reflux for an additional 2 h
  5. waitAfter 2 h
  6. temperaturethe reaction is chilled in an ice water bath
  7. temperaturethe suspension is chilled in an ice water bath
  8. filtrationfiltered
  9. washthe solids are washed
  10. temperaturewith minimal chilled water
  11. customThe solids are then dried in vacuo

Sources & evidence

ORD record
ord-4ba7a54f88884a02bb5de9e239c34ac7
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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