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

HRID 1986376

反応式

HRID 1986376 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
175 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-5df70ff7e3d749c8bb1d2c5b4da7583c
出典データセット
uspto-grants-2009_06
特許番号
US07547779B2

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