Piconol → 2-(2-Pyridylmethoxy)-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine

HRID 917588Notes

Reaction equation

HRID 917588 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.[H-].[Na+].CS([C:15]1[N:20]=[C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([Cl:31])[CH:24]=2)[C:18]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:17][N:16]=1)(=O)=O>O1CCCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[N:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:2][O:1][C:15]1[N:20]=[C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([Cl:31])[CH:24]=2)[C:18]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:17][N:16]=1

Participants

6

Reactant 3

HCID 11474PiconolHCID 24758Sodium hydrideHCID 17848304Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfonyl)pyrimidine-5-carboxylate

Product 1

HCID 178483472-(2-Pyridylmethoxy)-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 2-hydroxymethylpyridine 32 mg and sodium hydride (suspension in 60% oil) 11.8 mg in tetrahydrofuran 2.5 ml is stirred at room temperature for 5 minutes. To the mixture is added at room temperature a solution of 2-methylsulfonyl-5-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)pyrimidine (prepared in the above (2)) 118 mg in tetrahydrofuran 2.5 ml, and the mixture is stirred for 30 minutes at room temperature. The reaction mixture is diluted with an aqueous 10% citric acid solution and extracted twice with ethyl acetate. The combined organic layer is washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is purified by silica gel chromatography (solvent; chloroform:ethyl acetate=4:1→1:2) and concentrated in vacuo to give 2-(2-pyridylmethoxy)-5-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)pyrimidine as a colorless caramel, 106 mg.

Workup

  1. stirringthe mixture is stirred for 30 minutes at room temperature
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layer is washed with water
  4. dry with materialan aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography (solvent; chloroform:ethyl acetate=4:1→1:2)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4341d33e38c144ec87b6881119a1572d
Source dataset
uspto-grants-2007_09
Patent number
US07273868B2

Reaction notes

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