Triethylamine → Tert-butyl 3-(4-(5-(3-amino-6-(4-((1-(tert-butoxycarbonyl)piperidin-3-yl)sulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)phenyl)morpholine-4-carboxylate

HRID 78724ノート

反応式

HRID 78724 の反応式
C(OP(C#N)(=O)OCC)C.[NH2:11][C:12]1[N:13]=[CH:14][C:15]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH:31]3[CH2:36][CH2:35][CH2:34][N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32]3)(=[O:30])=[O:29])=[CH:24][CH:23]=2)=[N:16][C:17]=1[C:18]([NH:20][NH2:21])=[O:19].[C:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][O:54][CH2:53][CH:52]1[C:57]1[CH:65]=[CH:64][C:60]([C:61](O)=O)=[CH:59][CH:58]=1)=[O:50])([CH3:47])([CH3:46])[CH3:45].CCN(CC)CC>CN(C=O)C.O.C(OCC)(=O)C>[NH2:11][C:12]1[C:17]([C:18]2[O:19][C:61]([C:60]3[CH:59]=[CH:58][C:57]([CH:52]4[CH2:53][O:54][CH2:55][CH2:56][N:51]4[C:49]([O:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:50])=[CH:65][CH:64]=3)=[N:21][N:20]=2)=[N:16][C:15]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH:31]3[CH2:36][CH2:35][CH2:34][N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32]3)(=[O:30])=[O:29])=[CH:24][CH:23]=2)=[CH:14][N:13]=1

参加物

8

反応物 4

HCID 8471Triethylamine4 回HCID 76257Diethyl cyanophosphonate4 回HCID 86682780Tert-butyl 3-[4-[5-amino-6-(hydrazinecarbonyl)pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylateHCID 86682782HCID 86682782、化合物

生成物 1

HCID 86682781Tert-butyl 3-(4-(5-(3-amino-6-(4-((1-(tert-butoxycarbonyl)piperidin-3-yl)sulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)phenyl)morpholine-4-carboxylate収率 51.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

diethylcyanophosphonate (41.07 mg, 37.64 μL, 0.2518 mmol) was added to a solution of tert-butyl 3-[4-[5-amino-6-(hydrazinecarbonyl)pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (100 mg, 0.2098 mmol), 4-(4-tert-butoxycarbonylmorpholin-3-yl)benzoic acid (64.48 mg, 0.2098 mmol) and Et3N (25.48 mg, 35.10 μL, 0.2518 mmol) in DMF (1.500 mL) and the resulting solution stirred at ambient temperature for 20 minutes. A further portion of diethylcyanophosphonate (68.44 mg, 62.73 μL, 0.4196 mmol) and Et3N (42.46 mg, 58.48 μL, 0.4196 mmol) were added and the reaction mixture stirred at 55° C. for 20 hours. Further portions of Et3N (42.46 mg, 58.48 μL, 0.4196 mmol) and diethylcyanophosphonate (68.44 mg, 62.73 μL, 0.4196 mmol) were added and the reaction mixture stirred at 55° C. for a further 3 hours. Further portions of Et3N (42.46 mg, 58.48 μL, 0.4196 mmol) and diethylcyanophosphonate (68.44 mg, 62.73 μL, 0.4196 mmol) were added and the reaction mixture stirred at 55° C. for a further 4.5 hours. The reaction mixture was cooled to ambient temperature and diluted with water and ethyl acetate and the layers separated. The aqueous layer was extracted further with ethyl acetate (×2) and the combined organic extracts were washed with water (×2), brine (×2), dried over MgSO4, and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 80% EtOAc/Petroleum Ether, loaded in DCM) to give the sub-title product as a yellow solid (81 mg, 51% Yield). LC/MS m/z 748.1 [M+1]+.

後処理

  1. stirringthe reaction mixture stirred at 55° C. for 20 hours
  2. stirringthe reaction mixture stirred at 55° C. for a further 3 hours
  3. stirringthe reaction mixture stirred at 55° C. for a further 4.5 hours
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted further with ethyl acetate (×2)
  7. washthe combined organic extracts were washed with water (×2), brine (×2)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (ISCO Companion, 24 g column, eluting with 0 to 80% EtOAc/Petroleum Ether, loaded in DCM)

出典と根拠

ORDレコード
ord-bff275e8aa2c484b8cee94f4ebec1caa
出典データセット
uspto-grants-2014_09
特許番号
US08841449B2

反応ノート

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