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

HRID 1811754Notes

Reaction equation

HRID 1811754 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.CN(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][CH3:20]

Participants

6

Reactant 4

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

Product 1

HCID 592246605-[2-Amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-methoxy-4-methylbenzoic acid methyl esterYield 85.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-(2-Amino-6-chloropyrimidin-4-yl)-2-methoxy-4-methylbenzoic acid methyl ester (154 mg, 0.5 mmol) obtained in Example 1-2 and 3-hydroxybenzenethiol (0.25 ml, 2.5 mmol) were placed in a reaction vessel, and then N,N-dimethylformamide (1.0 ml) and triethylamine (0.35 ml, 2.5 mmol) were added thereto. The solution was stirred at room temperature for 24 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. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate) to yield 5-[2-amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-methoxy-4-methylbenzoic acid methyl ester (170 mg) as a yellow 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. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate)

Sources & evidence

ORD record
ord-faae6e0ece3c44b1ba588b4fc72866c9
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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