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

HRID 2076731Notes

Reaction equation

HRID 2076731 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 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 in vacuo, and the residue is washed with n-hexane to give 4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonyl-2-methylthiopyrimidine (38.34 g).

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. extractionextracted 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 in vacuo
  9. washthe residue is washed with n-hexane

Sources & evidence

ORD record
ord-f3bdacdccae0458ba1cd638a76ffe4dd
Source dataset
uspto-grants-2011_04
Patent number
US07927623B2

Reaction notes

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