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

HRID 1272872ノート

反応式

HRID 1272872 の反応式
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

参加物

7

反応物 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

生成物 1

HCID 207890371-(5-(1H-1,2,4-Triazol-5-yl)(1H-indazol-3-yl))-3-(2-pyrrolidinylethoxy)benzene収率 46%

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), 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]+.

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. 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

出典と根拠

ORDレコード
ord-7e9b048f58e7484bafb6436e539b9f83
出典データセット
uspto-grants-2007_04
特許番号
US07208513B2

反応ノート

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