Dichloromethane → 4-chloro-5-[N-(2-pyrimidinylmethyl)carbamoyl]-6-methoxy-2-methylthiopyrimidine

HRID 917656Notes

Reaction equation

HRID 917656 reaction equation
[Cl:1][C:2]1[C:7]([C:8](Cl)=[O:9])=[C:6]([O:11][CH3:12])[N:5]=[C:4]([S:13][CH3:14])[N:3]=1.C(Cl)Cl.[NH2:18][CH2:19][C:20]1[N:25]=[CH:24][CH:23]=[CH:22][N:21]=1.C(N(CC)CC)C>O>[Cl:1][C:2]1[C:7]([C:8](=[O:9])[NH:18][CH2:19][C:20]2[N:25]=[CH:24][CH:23]=[CH:22][N:21]=2)=[C:6]([O:11][CH3:12])[N:5]=[C:4]([S:13][CH3:14])[N:3]=1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 46580472-PyrimidinemethanamineHCID 178482844-Chloro-5-chloroformyl-6-methoxy-2-methylthiopyrimidine

Product 1

HCID 211000644-chloro-5-[N-(2-pyrimidinylmethyl)carbamoyl]-6-methoxy-2-methylthiopyrimidine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of whole amount of 4-chloro-5-chloroformyl-6-methoxy-2-methylthiopyrimidine (prepared in the above (4)) and methylene chloride 10 ml is dropped a mixture of 2-aminomethylpyrimidine 930 mg, triethylamine 2.38 ml and methylene chloride 10 ml over a period of 5 minutes on an ice bath, and the mixture is stirred for 20 minutes. The mixture is further stirred at room temperature for 40 minutes. The reaction mixture is diluted with water and the water layer is extracted with methylene chloride. The organic layer is dried and concentrated in vacuo. The residue is separated with silica gel chromatography (solvent; chloroform:ethyl acetate=1:1) and recrystallized from a mixture of methylene chloride, ethyl acetate and isopropyl ether to give 4-chloro-5-[N-(2-pyrimidinylmethyl)carbamoyl]-6-methoxy-2-methylthiopyrimidine as a colorless crystalline powder, 1.56 g. mp 176-177° C.

Workup

  1. additionis dropped
  2. stirringThe mixture is further stirred at room temperature for 40 minutes
  3. extractionthe water layer is extracted with methylene chloride
  4. customThe organic layer is dried
  5. concentrationconcentrated in vacuo
  6. customThe residue is separated with silica gel chromatography (solvent; chloroform:ethyl acetate=1:1)
  7. customrecrystallized from a mixture of methylene chloride, ethyl acetate and isopropyl ether

Sources & evidence

ORD record
ord-48609a4ab1fd45e9a89531e9764cbafa
Source dataset
uspto-grants-2007_09
Patent number
US07273868B2

Reaction notes

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