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

HRID 1811739Notes

Reaction equation

HRID 1811739 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].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[C:33]([O:37][C:38](=[O:43])[NH:39][CH2:40][CH2:41][SH:42])([CH3:36])([CH3:35])[CH3:34]>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:42][CH2:41][CH2:40][NH:39][C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:43])[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 11430Potassium CarbonateHCID 3017761N-(tert-butoxycarbonyl)-2-aminoethanethiolHCID 59224675HCID 59224675, compound

Product 1

HCID 592246725-[2-Amino-6-(2-tert-butoxycarbonylaminoethylsulfanyl)pyrimidin-4-yl]-2-methoxy-4-methylbenzoic acid methyl esterYield 83.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-(2-Amino-6-chloropyrimidin-4-yl)-2-methoxy-4-methylbenzoic acid methyl ester (118 mg, 0.38 mmol) obtained in Example 1-2 and potassium carbonate (212 mg, 1.5 mmol) were placed in a reaction vessel, and then N,N-dimethylformamide (1.0 ml) and (2-mercaptoethyl)carbamic acid tert-butyl ester (0.25 ml, 1.5 mmol) were added thereto. The mixture was stirred at room temperature for 15 hours. The reaction solution was diluted with ethyl acetate (100 ml), and sequentially washed twice with a saturated aqueous sodium bicarbonate solution (50 ml), twice with water (50 ml), and with a saturated aqueous sodium chloride solution (50 ml). The 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:n-hexane=1:2) to yield 5-[2-amino-6-(2-tert-butoxycarbonylaminoethylsulfanyl)pyrimidin-4-yl]-2-methoxy-4-methylbenzoic acid methyl ester (143 mg) as a yellow oily material.

Workup

  1. washsequentially washed twice with a saturated aqueous sodium bicarbonate solution (50 ml), twice with water (50 ml)
  2. dry with materialThe 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:n-hexane=1:2)

Sources & evidence

ORD record
ord-62ddfb5a98c74f4db6c969bc0b49ca4c
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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