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

HRID 2183228노트

반응식

HRID 2183228 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-ac6c8c70f8a94217880873236a84aee2
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06897231B2

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