Hydrochloric Acid → 1-(5-(1H-1,2,4-Triazol-5-YL)(1H-indazol-3-YL))-3-(2-piperidylethoxy)benzene

HRID 1353790ノート

反応式

HRID 1353790 の反応式
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[CH:26](O)[CH3:27].CCOC(/N=N/C(OCC)=O)=O.O1CCCCC1[N:47]1[C:55]2[C:50](=[CH:51][C:52]([C:56]3[N:60]=[CH:59][N:58](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:57]=3)=[CH:53][CH:54]=2)[C:49]([C:80]2[CH:81]=[C:82]([OH:86])[CH:83]=[CH:84][CH:85]=2)=[N:48]1.Cl>O1CCCC1>[NH:57]1[C:56]([C:52]2[CH:51]=[C:50]3[C:55](=[CH:54][CH:53]=2)[NH:47][N:48]=[C:49]3[C:80]2[CH:85]=[CH:84][CH:83]=[C:82]([O:86][CH2:27][CH2:26][CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25][NH:20]3)[CH:81]=2)=[N:60][CH:59]=[N:58]1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 3356821-(Piperidin-2-yl)ethan-1-olHCID 5462977Diethyl azodicarboxylateHCID 224797613-(1-(Tetrahydro-2H-pyran-2-yl)-5-(1-trityl-1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)phenol

生成物 1

HCID 224803261-(5-(1H-1,2,4-Triazol-5-YL)(1H-indazol-3-YL))-3-(2-piperidylethoxy)benzene収率 48.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 2-piperidylethanol (0.352 mL, 2.65 mmol) and diethylazodicarboxylate (0.418 mL, 2.65 mmol) were added to 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenol (0.400 g, 0.662 mmol). The mixture was stirred at ambient temperature for 23 h and poured into aqueous 6 N hydrochloric acid (30 mL). After stirring at ambient temperature for 4 h, the mixture was extracted with ether (3×). The aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL) and the pH adjusted to 11. The solution was extracted with ethyl acetate (3×) and the organic fractions were combined and dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica pretreated with 2% triethylamine/ethyl acetate elution followed by 0–20% methanol/ethyl acetate. The desired fractions were concentrated, dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated which gave the title compound (0.124 g, 48% yield). 1H NMR (CD3OD) δ 8.72 (m, 1H), 8.34 (s, 1H), 8.10 (dd, 1H), 7.67 (dd, 1H), 7.62 (dt, 1H), 7.58 (m, 1H), 7.47 (t, 1H), 7.04 (m, 1H), 4.27 (t, 2H), 2.89 (t, 2H), 2.63 (m, 4H), 1.68 (m, 4H), 1.51 (m, 2H). ES-MS (m/z) 389 [M+1]+

後処理

  1. stirringAfter stirring at ambient temperature for 4 h
  2. extractionthe mixture was extracted with ether (3×)
  3. additionThe aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL)
  4. extractionThe solution was extracted with ethyl acetate (3×)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica
  9. washpretreated with 2% triethylamine/ethyl acetate elution
  10. concentrationThe desired fractions were concentrated
  11. dissolutiondissolved in ethyl acetate
  12. washwashed with aqueous sodium bicarbonate
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. customevaporated which

出典と根拠

ORDレコード
ord-42e3d533ed9d4df6aac3afbb8ea7534c
出典データセット
uspto-grants-2007_05
特許番号
US07220771B2

反応ノート

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