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

HRID 1272876Notes

Reaction equation

HRID 1272876 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH:26](O)[CH2:27][CH3:28])[CH2:21]1.CCOC(/N=N/C(OCC)=O)=O.O1CCCCC1[N:48]1[C:56]2[C:51](=[CH:52][C:53]([C:57]3[N:61]=[CH:60][N:59](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:58]=3)=[CH:54][CH:55]=2)[C:50]([C:81]2[CH:82]=[C:83]([OH:87])[CH:84]=[CH:85][CH:86]=2)=[N:49]1.Cl>O1CCCC1>[NH:58]1[C:57]([C:53]2[CH:52]=[C:51]3[C:56](=[CH:55][CH:54]=2)[NH:48][N:49]=[C:50]3[C:81]2[CH:86]=[CH:85][CH:84]=[C:83]([O:87][CH2:28][CH2:27][CH2:26][CH:22]3[CH2:23][CH2:24][CH2:25][NH:20][CH2:21]3)[CH:82]=2)=[N:61][CH:60]=[N:59]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 211865023-PiperidylpropanolHCID 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 224802791-(5-(1H-1,2,4-Triazol-5-yl)(1H-indazol-3-yl))-3-(3-piperidylpropoxy)benzeneYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 3-piperidylpropanol (0.379 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 24 h and poured into aqueous 6 N hydrochloric acid (25 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 (25 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 elution. The desired fractions were concentrated, dissolved in ethyl acetate, washed with aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and evaporated to give the title compound (0.0847 g, 32% yield). 1H NMR (CD3OD) δ 8.71 (m, 1H), 8.34 (s, 1H), 8.10 (dd, 1H), 7.67 (dd, 1H), 7.60 (dt, 1H), 7.53 (m, 1H), 7.45 (t, 1H), 7.01 (m, 1H), 4.14 (t, 2H), 2.61 (m, 2H), 2.53 (s, 4H), 2.05 (m, 2H), 1.65 (m, 4H), 1.50 (m, 2H). ES-MS (m/z) 403 [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 (25 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. washfollowed by 0–20% methanol/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

Sources & evidence

ORD record
ord-1f4f4956fd6e484f9f1e624a7d313491
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

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