Piconol → 2-Methylthio-4-(3-chloro-4-methoxybenzylamino)-5-(2-pyridylmethoxycarbonyl)pyrimidine

HRID 1352739Notes

Reaction equation

HRID 1352739 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([Cl:19])[CH:12]=2)[C:6]([C:20]([OH:22])=[O:21])=[CH:5][N:4]=1.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.CN(C1C=CC=CN=1)C.[N:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[CH2:50]O>O1CCCC1.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:1][S:2][C:3]1[N:8]=[C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([Cl:19])[CH:12]=2)[C:6]([C:20]([O:22][CH2:50][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][N:44]=2)=[O:21])=[CH:5][N:4]=1

Participants

9

Reactant 4

HCID 11474PiconolHCID 218852-DimethylaminopyridineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 226655724-((3-Chloro-4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylic acid

Product 1

HCID 178483432-Methylthio-4-(3-chloro-4-methoxybenzylamino)-5-(2-pyridylmethoxycarbonyl)pyrimidine

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-carboxypyrimidine (prepared in Example 79) 0.100 g and triethylamine 82 μl in tetrahydrofuran 2.0 ml is treated under room temperature with 2,4,6-trichlorobenzoyl chloride 51 μl and then dimethylaminopyridine about 1 mg is added thereto, followed by stirring for 10 minutes. After addition of 2-pyridinemethanol 31 μl, the mixture is stirred for 12 hours. Ethyl acetate and water are added thereto and the organic layer is separated, washed with sodium hydrogen carbonate solution, brine. The organic layer is dried over anhydrous sodium sulfate and in vacuo. The residue is purified with silica gel chromatography (solvent; chloroform:ethyl acetate=5:1–2:1) and recrystallized from ethyl acetate-isopropyl ether to give 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-(2-pyridylmethoxycarbonyl)pyrimidine as a colorless needle, 0.5183 g. mp117–118° C.

Workup

  1. stirringthe mixture is stirred for 12 hours
  2. customthe organic layer is separated
  3. washwashed with sodium hydrogen carbonate solution, brine
  4. dry with materialThe organic layer is dried over anhydrous sodium sulfate and in vacuo
  5. customThe residue is purified with silica gel chromatography (solvent; chloroform:ethyl acetate=5:1–2:1)
  6. customrecrystallized from ethyl acetate-isopropyl ether

Sources & evidence

ORD record
ord-38caa3bcdfad4d71bf6ce9fd4799a052
Source dataset
uspto-grants-2007_05
Patent number
US07220736B2

Reaction notes

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