Citric Acid → Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfanyl)pyrimidine-5-carboxylate

HRID 431050Notes

Reaction equation

HRID 431050 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH2:19][NH2:20].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C(N(CC)CC)C.ClC1C=C(C=CC=1OC)CN>[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH2:19][NH:20][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1

Participants

7

Reactant 3

HCID 311Citric AcidHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 7380383-Chloro-4-methoxybenzylamine

Product 1

HCID 22025927Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfanyl)pyrimidine-5-carboxylateYield 95.7%

Reagents, catalysts & solvents 3

HCID 7380383-Chloro-4-methoxybenzylamineCatalystHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 4-chloro-5-ethoxycarbonyl-2-methylthiopyrimidine (25.33 g) in N,N-dimethylformamide (85 ml) are added a solution of 3-chloro-4-methoxybenzylamine (19.62 g) in N,N-dimethylformamide (15 ml) and triethylamine (16.7 ml) under ice-cooling. The mixture is stirred at room temperature for 20 minutes, and thereto is added 3-chloro-4-methoxybenzylamine (940 mg), and the mixture is further stirred for 15 minutes. To the mixture is further added said amine (940 mg), and the mixture is stirred for 15 minutes. The reaction mixture is poured into a mixture of ice water and citric acid, and the mixture is extracted with ethyl acetate. The extract is washed successively with a 10% aqueous citric acid solution, water and brine, and dried over anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, and the residue is washed with n-hexane to give 4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonyl-2-methylthiopyrimidine (38.34 g), m.p. 86° C.

Workup

  1. temperaturecooling
  2. stirringthe mixture is further stirred for 15 minutes
  3. additionTo the mixture is further added
  4. stirringthe mixture is stirred for 15 minutes
  5. extractionthe mixture is extracted with ethyl acetate
  6. washThe extract is washed successively with a 10% aqueous citric acid solution, water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent is evaporated under reduced pressure
  9. washthe residue is washed with n-hexane

Sources & evidence

ORD record
ord-d0ab4338e49d4c2c949b2f2ffaf343fb
Source dataset
uspto-grants-2003_12
Patent number
US06656935B2

Reaction notes

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