Binap, (A+-)- → [2-(4-Amino-furazan-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]thiophenol

HRID 1986376Notes

Reaction equation

HRID 1986376 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([C:13]3[C:14]([NH2:18])=[N:15][O:16][N:17]=3)[N:10]([CH2:11][CH3:12])[C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC([Si](C)(C)O[C:71]1[CH:72]=[C:73]([SH:77])[CH:74]=[CH:75][CH:76]=1)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:18][C:14]1[C:13]([C:9]2[N:10]([CH2:11][CH3:12])[C:4]3[CH:3]=[C:2]([C:72]4[CH:71]=[CH:76][CH:75]=[CH:74][C:73]=4[SH:77])[N:7]=[CH:6][C:5]=3[N:8]=2)=[N:17][O:16][N:15]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 160998514-(6-Bromo-1-Ethyl-1h-Imidazo[4,5-C]pyridin-2-Yl)-1,2,5-Oxadiazol-3-AmineHCID 219768683-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]benzenethiolHCID 23676156Sodium t-butoxide

Product 1

HCID 136400621[2-(4-Amino-furazan-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]thiophenolYield 26.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
175 °C

Procedure

Under Ar, a suspension of the product from Example 9, Step 2 (15 mg, 48.5 μmol) in 1,4-dioxane (0.5 mL) and toluene (2.0 mL) was treated with tris(dibenzylidene-acetone)dipalladium (4.6 mg, 5 μmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 10 μmol), 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}benzenethiol (14 ml, 58.2 μmol), and sodium tert-butoxide (6.6 mg, 67.9 μmol). This mixture was then heated to 175° C. by microwave for 45 min. After cooling to rt, the reaction mixture was concentrated, redissolved in THF (3 mL) and treated with TBAF (0.5 mL, 1.0 M in THF) for 1 h. The reaction mixture was diluted with ethyl acetate (30 ml), washed with brine and the organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC to afford the title compound (4.4 mg, 16%). MS (ES+) m/e 355 [M+H]+.

Workup

  1. temperatureAfter cooling to rt
  2. concentrationthe reaction mixture was concentrated
  3. dissolutionredissolved in THF (3 mL)
  4. additiontreated with TBAF (0.5 mL, 1.0 M in THF) for 1 h
  5. additionThe reaction mixture was diluted with ethyl acetate (30 ml)
  6. washwashed with brine
  7. dry with materialthe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5df70ff7e3d749c8bb1d2c5b4da7583c
Source dataset
uspto-grants-2009_06
Patent number
US07547779B2

Reaction notes

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