Dimethylformamide → 5-{2-Amino-6-[3-(3-tert-butoxycarbonylaminopropoxy)phenylsulfanyl]pyrimidin-4-yl}-2-ethoxy-4-methylbenzoic acid methyl ester

HRID 1811757Notes

Reaction equation

HRID 1811757 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([S:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=3)[N:13]=[C:12]([NH2:24])[N:11]=2)[C:7]([CH3:25])=[CH:6][C:5]=1[O:26][CH2:27][CH3:28].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.[C:41]([O:45][C:46](=[O:52])[NH:47][CH2:48][CH2:49][CH2:50]Br)([CH3:44])([CH3:43])[CH3:42]>C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([S:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:50][CH2:49][CH2:48][NH:47][C:46]([O:45][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:52])[CH:18]=3)[N:13]=[C:12]([NH2:24])[N:11]=2)[C:7]([CH3:25])=[CH:6][C:5]=1[O:26][CH2:27][CH3:28]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 592246545-[2-Amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-ethoxy-4-methylbenzoic acid methyl ester

Product 1

HCID 592246485-{2-Amino-6-[3-(3-tert-butoxycarbonylaminopropoxy)phenylsulfanyl]pyrimidin-4-yl}-2-ethoxy-4-methylbenzoic acid methyl esterYield 94.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

5-[2-Amino-6-(3-hydroxyphenylsulfanyl)pyrimidin-4-yl]-2-ethoxy-4-methylbenzoic acid methyl ester (110 mg, 0.27 mmol) obtained in Step 1 above, cesium carbonate (133 mg, 0.41 mmol), and N,N-dimethylformamide (1.2 ml) were added to a reaction vessel, and then 3-bromopropylcarbamic acid tert-butyl ester (97 mg, 0.41 mmol) was added thereto. The resulting mixture was stirred at room temperature for 4 hours. The reaction solution was diluted with ethyl acetate (100 ml), and sequentially washed twice with a saturated aqueous ammonium chloride solution (50 ml), twice with water (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: n-hexane:ethyl acetate=2:3) to yield 5-{2-amino-6-[3-(3-tert-butoxycarbonylaminopropoxy)phenylsulfanyl]pyrimidin-4-yl}-2-ethoxy-4-methylbenzoic acid methyl ester (145 mg).

Workup

  1. washsequentially washed twice with a saturated aqueous ammonium chloride solution (50 ml), twice with water (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: n-hexane:ethyl acetate=2:3)

Sources & evidence

ORD record
ord-e32723fdcbb9407db4923ecae3eeaa44
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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