Hydrochloric Acid → 1-(5-(1H-1,2,4-triazol-5-yl)(1H-indazol-3-yl))-3-(2-morpholin-4-ylethoxy)benzene

HRID 1349724Notes

Reaction equation

HRID 1349724 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][OH:28])[CH2:22][CH2:21]1.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](O)[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:81]=[CH:82][CH:83]=[C:84]([O:28][CH2:27][CH2:26][N:23]3[CH2:24][CH2:25][O:20][CH2:21][CH2:22]3)[CH:85]=2)=[N:60][CH:59]=[N:58]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 5462977Diethyl azodicarboxylateHCID 224797613-(1-(Tetrahydro-2H-pyran-2-yl)-5-(1-trityl-1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)phenol

Product 1

HCID 117108581-(5-(1H-1,2,4-triazol-5-yl)(1H-indazol-3-yl))-3-(2-morpholin-4-ylethoxy)benzeneYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 2-morpholinoethanol (0.321 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 gel pretreated with 2% triethylamine/hexanes followed by 0–20% ethyl acetate/hexanes and gave the title compound (0.0774 g, 30% yield). 1H NMR (CD3OD) δ 8.72 (m, 1H), 8.36 (br s, 1H), 8.10 (dd, 1H), 7.68 (d, 1H), 7.62 (dt, 1H), 7.56 (t, 1H), 7.46 (t, 1H), 7.04 (m, 1H), 4.28 (t, 2H), 3.72 (t, 4H), 2.89 (t, 2H), 2.65 (t, 4H). ES-MS (m/z) 391 [M+1]+

Workup

  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 gel

Sources & evidence

ORD record
ord-efe68bf83efe491690bd7df394191f45
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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