Dimethylformamide → 5-[2-Amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-ethoxy-4-methylbenzoic acid methyl ester

HRID 1811756Notes

Reaction equation

HRID 1811756 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14](Cl)[N:13]=[C:12]([NH2:17])[N:11]=2)[C:7]([CH3:18])=[CH:6][C:5]=1[O:19][CH3:20].[OH:22][C:23]1[CH:24]=[C:25]([SH:29])[CH:26]=[CH:27][CH:28]=1.[CH3:30]N(C)C=O.C(N(CC)CC)C>C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([S:29][C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([OH:22])[CH:24]=3)[N:13]=[C:12]([NH2:17])[N:11]=2)[C:7]([CH3:18])=[CH:6][C:5]=1[O:19][CH2:20][CH3:30]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 27366133-HydroxybenzenethiolHCID 59224675HCID 59224675, compound

Product 1

HCID 592246545-[2-Amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-ethoxy-4-methylbenzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-(2-Amino-6-chloropyrimidin-4-yl)-2-methoxy-4-methylbenzoic acid methyl ester (96.5 mg, 0.3 mmol) obtained in Example 1-2 and 3-hydroxybenzenethiol (0.15 ml, 1.5 mmol) were placed in a reaction vessel, and then N,N-dimethylformamide (0.6 ml) and triethylamine (0.2 ml, 1.5 mmol) were added thereto. The solution was stirred at room temperature for 20 hours. The reaction solution was diluted with ethyl acetate (100 ml), and sequentially washed twice with water (50 ml), twice with a saturated aqueous sodium bicarbonate solution (50 ml), and with a saturated aqueous sodium chloride solution (50 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=1:1 to 1:2) to yield 5-[2-amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-ethoxy-4-methylbenzoic acid methyl ester (110 mg) as a white solid material.

Workup

  1. washsequentially washed twice with water (50 ml), twice with a saturated aqueous sodium bicarbonate solution (50 ml)
  2. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=1:1 to 1:2)

Sources & evidence

ORD record
ord-264bfbed5b6e48b583eff27b7495b020
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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