Ammonia → Methyl 6-amino-2-chloropyrimidine-4-carboxylate

HRID 245279

Reaction equation

HRID 245279 reaction equation
[NH3:1].[CH3:2][O:3][C:4]([C:6]1[CH:11]=[C:10](Cl)[N:9]=[C:8]([Cl:13])[N:7]=1)=[O:5]>CS(C)=O>[CH3:2][O:3][C:4]([C:6]1[CH:11]=[C:10]([NH2:1])[N:9]=[C:8]([Cl:13])[N:7]=1)=[O:5]

Participants

4

Reactant 2

HCID 222Ammonia2×HCID 239689Methyl 2,4-dichloropyrimidine-6-carboxylate

Product 1

HCID 53396493Methyl 6-amino-2-chloropyrimidine-4-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Ammonia was slowly bubbled through a solution of 2,6-dichloro-pyrimidine-4-carboxylic acid methyl ester (20.0 g, 97 mmol, see H. Gershon, J. Org. Chem. 1962, 27, 3507-3510 for preparation) in DMSO (100 mL) cooled with an ice bath to maintain the temperature below 70° C. When the temperature of the reaction solution began to decline, no additional ammonia was added. When the temperature of the reaction solution reached 44° C., the ice bath was removed. When the temperature of the reaction solution reached 32° C., the reaction mixture was diluted with 200 mL of water and filtered. The filtered product was washed with water, washed with ethyl acetate, and dried under vacuum to provide the title compound (14.4 g, 79% yield) that was used without further purification. Flash chromatography on silica gel yielded an analytically pure sample of the title compound: 1H NMR (DMSO-d6) δ 7.7 (br s, 2H), 7.00 (s, 1H), 3.84 (s, 3H).

Workup

  1. temperaturecooled with an ice bath
  2. temperatureto maintain the temperature below 70° C
  3. customreached 44° C.
  4. customthe ice bath was removed
  5. customreached 32° C.
  6. additionthe reaction mixture was diluted with 200 mL of water
  7. filtrationfiltered
  8. washThe filtered product was washed with water
  9. washwashed with ethyl acetate
  10. customdried under vacuum

Sources & evidence

ORD record
ord-9d9db4e9deeb485c807ed72b4ad5a9d8
Source dataset
uspto-grants-2014_02
Patent number
US08658791B2

Linked notes

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