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

HRID 1349727노트

반응식

HRID 1349727 반응식
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:20]1([CH:25](O)[CH3:26])[CH2:24][CH2:23][CH2:22][CH2:21]1.CCOC(/N=N/C(OCC)=O)=O.O1CCCCC1[N:46]1[C:54]2[C:49](=[CH:50][C:51]([C:55]3[N:59]=[CH:58][N:57](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:56]=3)=[CH:52][CH:53]=2)[C:48]([C:79]2[CH:80]=[C:81]([OH:85])[CH:82]=[CH:83][CH:84]=2)=[N:47]1.Cl>O1CCCC1>[NH:56]1[C:55]([C:51]2[CH:50]=[C:49]3[C:54](=[CH:53][CH:52]=2)[NH:46][N:47]=[C:48]3[C:79]2[CH:84]=[CH:83][CH:82]=[C:81]([O:85][CH2:26][CH2:25][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[CH:80]=2)=[N:59][CH:58]=[N:57]1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 17981833PyrrolidinylethanolHCID 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 207890371-(5-(1H-1,2,4-Triazol-5-yl)(1H-indazol-3-yl))-3-(2-pyrrolidinylethoxy)benzene수율 46%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), pyrrolidinylethanol (0.310 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 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 (0.114 g, 46% yield). 1H NMR (CD3OD) δ 8.72 (s, 1H), 8.34 (s, 1H), 8.09 (dd, 1H), 7.67 (d, 1H), 7.62 (d, 1H), 7.57 (m, 1H), 7.47 (t, 1H), 7.04 (m, 1H), 4.26 (t, 2H), 3.02 (t, 2H), 2.73 (m, 4H), 1.87 (m, 4H). ES-MS (m/z) 375 [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. concentrationThe desired fractions were concentrated
  10. dissolutiondissolved in ethyl acetate
  11. washwashed with aqueous sodium bicarbonate
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. customevaporated which

출처 및 근거

ORD 기록
ord-306593aef6cc4516825b2b615c5b844a
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07211594B2

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