Bis(trifluoroacetoxy)iodobenzene → Tert-butyl 3-((4-(5-((tert-butoxycarbonyl)amino)-6-(3-(2-hydroxyphenyl)isoxazol-5-yl)pyrazin-2-yl)phenyl)sulfonyl)piperidine-1-carboxylate

HRID 78718

反応式

HRID 78718 の反応式
C1C=CC(I(OC(C(F)(F)F)=O)OC(C(F)(F)F)=O)=CC=1.[C:22]([O:26][C:27]([N:29](C(OC(C)(C)C)=O)[C:30]1[N:31]=[CH:32][C:33]([C:38]2[CH:43]=[CH:42][C:41]([S:44]([CH:47]3[CH2:52][CH2:51][CH2:50][N:49]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:48]3)(=[O:46])=[O:45])=[CH:40][CH:39]=2)=[N:34][C:35]=1[C:36]#[CH:37])=[O:28])([CH3:25])([CH3:24])[CH3:23].[OH:67][C:68]1[CH:76]=[CH:75][CH:74]=[CH:73][C:69]=1/[CH:70]=[N:71]/[OH:72]>CO.O>[C:22]([O:26][C:27]([NH:29][C:30]1[N:31]=[CH:32][C:33]([C:38]2[CH:39]=[CH:40][C:41]([S:44]([CH:47]3[CH2:52][CH2:51][CH2:50][N:49]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:48]3)(=[O:45])=[O:46])=[CH:42][CH:43]=2)=[N:34][C:35]=1[C:36]1[O:72][N:71]=[C:70]([C:69]2[CH:73]=[CH:74][CH:75]=[CH:76][C:68]=2[OH:67])[CH:37]=1)=[O:28])([CH3:24])([CH3:25])[CH3:23]

参加物

5

反応物 3

HCID 102317Bis(trifluoroacetoxy)iodobenzene2 回HCID 86682774Tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-ethynyl-pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylateHCID 135408751Salicylaldoxime

生成物 1

HCID 136387756Tert-butyl 3-((4-(5-((tert-butoxycarbonyl)amino)-6-(3-(2-hydroxyphenyl)isoxazol-5-yl)pyrazin-2-yl)phenyl)sulfonyl)piperidine-1-carboxylate収率 78%

試薬・触媒・溶媒 1

HCID 22242641Methanol--water (1/1)溶媒

実験手順

PIFA was added to a stirred solution of tert-butyl 3-[4-[5-[bis(tert-butoxycarbonyl)amino]-6-ethynyl-pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (150 mg,) and (E)-2-hydroxybenzaldehyde oxime in MeOH/water (0.4 mL) and the reaction mixture stirred at ambient temperature for 1.5 hours. A further portion of PIFA was added and the reaction mixture stirred at ambient temperature for a further 1.5 hours. The reaction mixture was partitioned between ethylacetate and water and the layers separated. The aqueous layer was extracted with ethylacetate (×1) and the combined organic extracts dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 50% Petroleum/Petroleum Ether, loaded in DCM) to give tert-butyl 3-((4-(5-((tert-butoxycarbonyl)amino)-6-(3-(2-hydroxyphenyl)isoxazol-5-yl)pyrazin-2-yl)phenyl)sulfonyl)piperidine-1-carboxylate as an off-white solid (142 mg, 78%). LC/MS m/z 722.1 [M−56+1]+.

後処理

  1. stirringthe reaction mixture stirred at ambient temperature for a further 1.5 hours
  2. customThe reaction mixture was partitioned between ethylacetate and water
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with ethylacetate (×1)
  5. dry with materialthe combined organic extracts dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 50% Petroleum/Petroleum Ether, loaded in DCM)

出典と根拠

ORDレコード
ord-393fa319b5c546d5acf1eefcefdf473e
出典データセット
uspto-grants-2014_09
特許番号
US08841449B2

関連ノート

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