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

HRID 1986376

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HRID 1986376 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 312751,4-Dioxane용매

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온도
175 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-5df70ff7e3d749c8bb1d2c5b4da7583c
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07547779B2

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