tert-Butanol → HCID 24882936, compound

HRID 1927206Notes

Reaction equation

HRID 1927206 reaction equation
C(O)(C)(C)C.[C:6]([C:8]1[C:9]([NH2:14])=[N:10][CH:11]=[CH:12][CH:13]=1)#[CH:7].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]Cl)=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[N-:31]=[N+:32]=[N-:33].[Na+]>S([O-])([O-])(=O)=O.[Cu+2].[Cu].O>[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:31]2[CH:7]=[C:6]([C:8]3[C:9]([NH2:14])=[N:10][CH:11]=[CH:12][CH:13]=3)[N:33]=[N:32]2)=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 33557Sodium AzideHCID 700424-Benzyloxybenzyl chlorideHCID 124225263-Ethynylpyridin-2-amine

Product 1

HCID 24882936HCID 24882936, compoundYield 7.7%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24462Copper SulfateCatalystHCID 962WaterSolvent2×

Procedure

To a solution of a tert-butyl alcohol (500 μL), water (600 μL) and the 3-ethynyl-pyridin-2-ylamine (30 mg) described in Manufacturing Example 1-2 were added 1-benzyloxy-4-chloromethyl-benzene (59 mg), sodium azide (17 mg), copper sulfate (8 mg), and copper (13 mg) at room temperature, which was irradiated for 10 minutes at no higher than 125° C. with 100 W microwaves. Water was added to the reaction mixture, which was filtered through Celite. The filtrate thus obtained was extracted with ethyl acetate, and the organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate and filtered, and then the solvent was evaporated from the filtrate under a reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% TFA), which was then further purified by silica gel column chromatography (ethyl acetate:methanol=15:1) to obtain the titled compound (7 mg).

Workup

  1. customwhich was irradiated for 10 minutes at no higher than 125° C. with 100 W microwaves
  2. filtrationwas filtered through Celite
  3. customThe filtrate thus obtained
  4. extractionwas extracted with ethyl acetate
  5. washthe organic layer was washed with saturated brine
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated from the filtrate under a reduced pressure
  9. customThe residue was purified by reverse-phase high performance liquid chromatography (
  10. additioncontaining 0.1% TFA), which
  11. customwas then further purified by silica gel column chromatography (ethyl acetate:methanol=15:1)

Sources & evidence

ORD record
ord-5269f56cbcc84f3b882434565f4e9f07
Source dataset
uspto-grants-2012_05
Patent number
US08183264B2

Reaction notes

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